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exposure.
INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. COVID-19 TREATMENTS: CLINICAL EFFICACY OF HYDROXYCH Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions . None of the 15 patients receiving HC Q+AZ were transferred to intensive care or died.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. COVID-19 TREATMENTS: CLINICAL EFFICACY OF HYDROXYCH Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions . None of the 15 patients receiving HC Q+AZ were transferred to intensive care or died.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. COVID-19 TREATMENTS: CLINICAL EFFICACY OF HYDROXYCH Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions . None of the 15 patients receiving HC Q+AZ were transferred to intensive care or died.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. COVID-19 TREATMENTS: CLINICAL EFFICACY OF HYDROXYCH Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions . None of the 15 patients receiving HC Q+AZ were transferred to intensive care or died.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. COVID-19 TREATMENTS: CLINICAL EFFICACY OF HYDROXYCH Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions . None of the 15 patients receiving HC Q+AZ were transferred to intensive care or died.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. ZN2+ INHIBITS CORONAVIRUS AND ARTERIVIRUS RNA POLYMERASE Shows that the combination of Zn2+ and a zinc ionophore (pyrithione) at low concentrations inhibits the replication of SARS-CoV and equine arteritis virus (EAV) in cell culture. Recommends further study of the use of zinc-ionophores as antiviral.. COVID-19 TREATMENTS: CLINICAL EFFICACY OF HYDROXYCH Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions . None of the 15 patients receiving HC Q+AZ were transferred to intensive care or died.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. ZN2+ INHIBITS CORONAVIRUS AND ARTERIVIRUS RNA POLYMERASE Shows that the combination of Zn2+ and a zinc ionophore (pyrithione) at low concentrations inhibits the replication of SARS-CoV and equine arteritis virus (EAV) in cell culture. Recommends further study of the use of zinc-ionophores as antiviral.. COVID-19 TREATMENTS: CLINICAL EFFICACY OF HYDROXYCH Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions . None of the 15 patients receiving HC Q+AZ were transferred to intensive care or died.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. ZN2+ INHIBITS CORONAVIRUS AND ARTERIVIRUS RNA POLYMERASE Shows that the combination of Zn2+ and a zinc ionophore (pyrithione) at low concentrations inhibits the replication of SARS-CoV and equine arteritis virus (EAV) in cell culture. Recommends further study of the use of zinc-ionophores as antiviral.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. ZN2+ INHIBITS CORONAVIRUS AND ARTERIVIRUS RNA POLYMERASE Shows that the combination of Zn2+ and a zinc ionophore (pyrithione) at low concentrations inhibits the replication of SARS-CoV and equine arteritis virus (EAV) in cell culture. Recommends further study of the use of zinc-ionophores as antiviral.. COVID-19 TREATMENTS: CLINICAL EFFICACY OF HYDROXYCH Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions . None of the 15 patients receiving HC Q+AZ were transferred to intensive care or died.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. ZN2+ INHIBITS CORONAVIRUS AND ARTERIVIRUS RNA POLYMERASE Shows that the combination of Zn2+ and a zinc ionophore (pyrithione) at low concentrations inhibits the replication of SARS-CoV and equine arteritis virus (EAV) in cell culture. Recommends further study of the use of zinc-ionophores as antiviral.. COVID-19 TREATMENTS: CLINICAL EFFICACY OF HYDROXYCH Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions . None of the 15 patients receiving HC Q+AZ were transferred to intensive care or died.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. ZN2+ INHIBITS CORONAVIRUS AND ARTERIVIRUS RNA POLYMERASE Shows that the combination of Zn2+ and a zinc ionophore (pyrithione) at low concentrations inhibits the replication of SARS-CoV and equine arteritis virus (EAV) in cell culture. Recommends further study of the use of zinc-ionophores as antiviral.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. ZN2+ INHIBITS CORONAVIRUS AND ARTERIVIRUS RNA POLYMERASE Shows that the combination of Zn2+ and a zinc ionophore (pyrithione) at low concentrations inhibits the replication of SARS-CoV and equine arteritis virus (EAV) in cell culture. Recommends further study of the use of zinc-ionophores as antiviral.. COVID-19 TREATMENTS: CLINICAL EFFICACY OF HYDROXYCH Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions . None of the 15 patients receiving HC Q+AZ were transferred to intensive care or died.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. ZN2+ INHIBITS CORONAVIRUS AND ARTERIVIRUS RNA POLYMERASE Shows that the combination of Zn2+ and a zinc ionophore (pyrithione) at low concentrations inhibits the replication of SARS-CoV and equine arteritis virus (EAV) in cell culture. Recommends further study of the use of zinc-ionophores as antiviral.. COVID-19 TREATMENTS: CLINICAL EFFICACY OF HYDROXYCH Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions . None of the 15 patients receiving HC Q+AZ were transferred to intensive care or died.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. ZN2+ INHIBITS CORONAVIRUS AND ARTERIVIRUS RNA POLYMERASE Shows that the combination of Zn2+ and a zinc ionophore (pyrithione) at low concentrations inhibits the replication of SARS-CoV and equine arteritis virus (EAV) in cell culture. Recommends further study of the use of zinc-ionophores as antiviral.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
IVERMECTIN FOR PREVENTION AND TREATMENT OF COVID-19 Systematic review and meta analysis of 21 RCTs finding mortality RR 0.32 , and prophylaxis case RR 0.14 . INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. ZN2+ INHIBITS CORONAVIRUS AND ARTERIVIRUS RNA POLYMERASE Shows that the combination of Zn2+ and a zinc ionophore (pyrithione) at low concentrations inhibits the replication of SARS-CoV and equine arteritis virus (EAV) in cell culture. Recommends further study of the use of zinc-ionophores as antiviral.. COVID-19 TREATMENTS: CLINICAL EFFICACY OF HYDROXYCH Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions . None of the 15 patients receiving HC Q+AZ were transferred to intensive care or died.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
IVERMECTIN FOR PREVENTION AND TREATMENT OF COVID-19 Systematic review and meta analysis of 21 RCTs finding mortality RR 0.32 , and prophylaxis case RR 0.14 . INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. ZN2+ INHIBITS CORONAVIRUS AND ARTERIVIRUS RNA POLYMERASE Shows that the combination of Zn2+ and a zinc ionophore (pyrithione) at low concentrations inhibits the replication of SARS-CoV and equine arteritis virus (EAV) in cell culture. Recommends further study of the use of zinc-ionophores as antiviral.. COVID-19 TREATMENTS: CLINICAL EFFICACY OF HYDROXYCH Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions . None of the 15 patients receiving HC Q+AZ were transferred to intensive care or died.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
IVERMECTIN FOR PREVENTION AND TREATMENT OF COVID-19 Systematic review and meta analysis of 21 RCTs finding mortality RR 0.32 , and prophylaxis case RR 0.14 . INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. ZN2+ INHIBITS CORONAVIRUS AND ARTERIVIRUS RNA POLYMERASE Shows that the combination of Zn2+ and a zinc ionophore (pyrithione) at low concentrations inhibits the replication of SARS-CoV and equine arteritis virus (EAV) in cell culture. Recommends further study of the use of zinc-ionophores as antiviral.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
IVERMECTIN FOR PREVENTION AND TREATMENT OF COVID-19 Systematic review and meta analysis of 21 RCTs finding mortality RR 0.32 , and prophylaxis case RR 0.14 . INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. ZN2+ INHIBITS CORONAVIRUS AND ARTERIVIRUS RNA POLYMERASE Shows that the combination of Zn2+ and a zinc ionophore (pyrithione) at low concentrations inhibits the replication of SARS-CoV and equine arteritis virus (EAV) in cell culture. Recommends further study of the use of zinc-ionophores as antiviral.. COVID-19 TREATMENTS: CLINICAL EFFICACY OF HYDROXYCH Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions . None of the 15 patients receiving HC Q+AZ were transferred to intensive care or died.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
IVERMECTIN FOR PREVENTION AND TREATMENT OF COVID-19 Systematic review and meta analysis of 21 RCTs finding mortality RR 0.32 , and prophylaxis case RR 0.14 . INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. ZN2+ INHIBITS CORONAVIRUS AND ARTERIVIRUS RNA POLYMERASE Shows that the combination of Zn2+ and a zinc ionophore (pyrithione) at low concentrations inhibits the replication of SARS-CoV and equine arteritis virus (EAV) in cell culture. Recommends further study of the use of zinc-ionophores as antiviral.. COVID-19 TREATMENTS: CLINICAL EFFICACY OF HYDROXYCH Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions . None of the 15 patients receiving HC Q+AZ were transferred to intensive care or died.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
IVERMECTIN FOR PREVENTION AND TREATMENT OF COVID-19 Systematic review and meta analysis of 21 RCTs finding mortality RR 0.32 , and prophylaxis case RR 0.14 . INHALED HYDROXYCHLOROQUINE TO IMPROVE EFFICACY AND REDUCE Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug.. ZN2+ INHIBITS CORONAVIRUS AND ARTERIVIRUS RNA POLYMERASE Shows that the combination of Zn2+ and a zinc ionophore (pyrithione) at low concentrations inhibits the replication of SARS-CoV and equine arteritis virus (EAV) in cell culture. Recommends further study of the use of zinc-ionophores as antiviral.. CONTINUOUS HYDROXYCHLOROQUINE OR COLCHICINE THERAPY DOES Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoidexposure.
COVID-19 studies: C19 studies: C19: IvermectinIVMVitamin DV.D
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00.250.50.7511.251.51.752+ Gautret66%0.34
2.4gviral+6/2014/16Improvement, RR Dose (4d)TreatmentControl Huang (RCT)92%0.08 4.0g (c)no
recov.0/106/12 Esper 64%0.36 2.0ghosp.8/41212/224Ashraf
68%0.32 1.6gdeath10/772/5Huang (ES)
59%0.41 2.0g (c)viral time32/3237/37 Guérin 61%0.39 2.4gdeath0/201/34Chen (RCT)
72%0.28 1.6gviral
time18/1812/12 Derwand79%0.21
1.6gdeath1/14113/377 Mitj(RCT) 16%0.84
2.0ghosp.8/13611/157Skipper (RCT)
37%0.63
3.2ghosp./death5/2318/234Hong
65%0.35 n/aviral+42/4248/48Bernabeu-Wittel
59%0.41
2.0gdeath18983 Yu (ES) 85%0.15 1.6gdeath1/73238/2,604Ly 56%0.44
2.4gdeath18/11629/110 Ip 55%0.45 n/adeath2/9744/970Heras
96%0.04 n/adeath8/7016/30Kirenga
26%0.74 n/arecov.
time29/2927/27 Sulaiman64%0.36
2.0gdeath7/1,81754/3,724Guisado-Vasco (ES)
67%0.33
n/adeath2/65139/542 SzenteFonseca 64%0.36
2.0ghosp.25/17589/542Cadegiani
81%0.19
1.6gdeath0/1592/137 Simova 94%0.06 2.4ghosp.0/332/5Omrani (RCT)
12%0.88 2.4ghosp.7/3044/152Agusti
68%0.32
2.0gprogression2/874/55 Su 85%0.15 1.6gprogression261355Amaravadi (DB RCT)
60%0.40 3.2gno
recov.3/156/12 Roy
2%0.98 n/arecov. time1415Mokhtari
70%0.30
2.0gdeath27/7,295287/21,464Million
83%0.17
2.4gdeath5/8,31511/2,114Early treatment66%0.34 266/20,2531,116/34,09766% improvementAll 29 hydroxychloroquine COVID-19 early treatment studieshcqmeta.com 6/5/21Tau2 = 0.62; I2 = 87.4%; Z = 5.87 (p < 0.0001)LowerRiskIncreased Risk
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00.250.50.7511.251.51.752+All studiesEarly treatmentEffects reportedin all COVID-19hydroxychloroquine studiesmin, Q1, median, Q3, maxLower RiskIncreased Riskhcqmeta.com 6/5/21Download Image
GLOBAL HCQ/CQ USELIMITED USEWIDELY USEDMIXED USEHCQ-LIKE PROPHYLAXISUNCLEARUSAGE AS OF FEB 2 2021 - SUBMIT CORRECTIONSHCQ-LIKE PROPHYLAXIS: 35MUNCLEAR: 762MLIMITED USE: 900MMIXED USE: 1.1BWIDELYUSED: 4.9B
Global HCQ/CQ studiesJune 5, 2021
@CovidAnalysis
Database of all HCQ COVID-19 studies. 300 studies, 222 peer reviewed, 250 comparing treatment and control groups. Submit updates/corrections below. HCQ is not effective when used very late with high dosages over a long period (RECOVERY/SOLIDARITY), effectiveness improves with earlier usage and improved dosing. Early treatment consistently shows positive effects. Negative evaluations typically ignore treatment time, often focusing on a subset of late stage studies. _In Vitro_ evidence made some believe that therapeutic levels would not be attained, however that was incorrect, e.g. see __.
Search: Restrict: All Early Late PrEP PEP 6/4 Early, Late, PrEP, PEP Covid Analysis (Preprint) (meta analysis - not included in studycount)
meta-analysis v112
HCQ for COVID-19: real-time meta analysis of 250 studies Details • 100% of the 29 early treatment studies report a positive effect (13 statistically significant in isolation). • Random effects meta-analysis with pooled effects using the most s.. 6/4 Details Source PDFEarly, Late, PrEP, PEP Early, Late, PrEP, PEP Covid Analysis (Preprint) (meta analysis - not included in study
count)
HCQ for COVID-19: real-time meta analysis of 250 studies • 100% of the 29 early treatment studies report a positive effect (13 statistically significant inisolation).
• Random effects meta-analysis with pooled effects using the most serious outcome reported shows 66% improvement for the 29 early treatment studies (RR 0.34 ). Results are similar after exclusion based sensitivity analysis: 67% (RR 0.33 ), and after restriction to 20 peer-reviewed studies: 65% (RR 0.35 ). Restricting to the 6 RCTs shows 46% improvement (RR 0.54 ). Restricting to the 13 mortality results shows 75% lower mortality (RR 0.25).
• Late treatment is less successful, with only 71% of the 169 studies reporting a positive effect. Very late stage treatment is not effective and may be harmful, especially when using excessive dosages. • The probability that an ineffective treatment generated results as positive as the 250 studies to date is estimated to be 1 in 1 quadrillion (_p_ = 0.00000000000000094). • 87% of Randomized Controlled Trials (RCTs) for early, PrEP, or PEP treatment report positive effects, the probability of this happening for an ineffective treatment is 0.0037. • There is substantial evidence of bias towards publishing negative results . 84% of prospective studies report positive effects, and only 72% of retrospective studies do. Studies from North America are 3.2 times more likely to report negative results than studies from the rest of the world combined, _p_ = 0.0000000243. • Negative meta analyses of HCQ generally choose a subset of trials, focusing on late treatment, especially trials with very late treatment and excessive dosages. • While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 5% of HCQ studies show zero events in the treatmentarm.
• Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. All practical, effective, and safe means should be used. Not doing so increases the risk of COVID-19 becoming endemic; and increases mortality, morbidity, and collateraldamage.
• All data to reproduce this paper and the sources are in the appendix . See for other meta analyses showing efficacy when HCQ is used early.Total
250 studies
3,993 authors
379,561 patients
Positive effects
187 studies
2,862 authors
266,059 patients
Early treatment
66% improvement
RR 0.34
Late treatment
22% improvement
RR 0.78
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Submit Corrections or Comments6/4 Late
Byakika-Kibwika et al., Research Square, doi:10.21203/rs.3.rs-506195/v1 (Preprint) recov. time, 0.0%, p=0.91 Safety and Efficacy of Hydroxychloroquine for Treatment of Non-Severe COVID-19 in Adults in Uganda: A Randomized Open Label PhaseII Clinical Trial
Details Small 105 patient RCT in Uganda showing no significant differences. No mortality was reported. The patients were very young (median age 32), recovering in a median time of 3 days with standard of care, so there is little room for atreatm..
6/4 Details SourceLate treatment study Late treatment study Byakika-Kibwika et al., Research Square, doi:10.21203/rs.3.rs-506195/v1 (Preprint) Safety and Efficacy of Hydroxychloroquine for Treatment of Non-Severe COVID-19 in Adults in Uganda: A Randomized Open Label Phase
II Clinical Trial
Small 105 patient RCT in Uganda showing no significant differences. No mortality was reported. The patients were very young (median age 32), recovering in a median time of 3 days with standard of care, so there is little room for a treatment to make improvements. Time since symptom onset is not specified, but the distribution of symptoms at baseline suggests that the enrollment is relatively late within a cohort of low risk patients. recovery time, no change, relative time 1.00, _p_ = 0.91, treatment36, control 29.
relative improvement in Ct value, 29.3% lower, RR 0.71, _p_ = 0.47, treatment 15, control 15. risk of COVID-19 case, 2.6% higher, RR 1.03, _p_ = 1.00, treatment 35 of 55 (63.6%), control 31 of 50 (62.0%), day 6. risk of COVID-19 case, 6.7% higher, RR 1.07, _p_ = 0.85, treatment 27 of 55 (49.1%), control 23 of 50 (46.0%), day 10. Byakika-Kibwika et al., 6/4/2021, Randomized Controlled Trial, Uganda, Africa, preprint, 17 authors.Share Tweet
Submit Corrections or Comments6/1 PrEP
Korkmaz et al., Authorea, doi:10.22541/au.162257516.68665404/v1(Preprint)
death, ↓82.1%, p=0.19 The effect of Hydroxychloroquine use due to rheumatic disease on the risk of Covid-19 infection and its course Details Retrospective 683 patients in a rheumatology department, 384 chronic HCQ users and 299 control patients, showing no mortality for HCQ users vs. 2 deaths in the control group, and significantly fewer cases for HCQ users. 6/1 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Korkmaz et al., Authorea, doi:10.22541/au.162257516.68665404/v1
(Preprint)
The effect of Hydroxychloroquine use due to rheumatic disease on the risk of Covid-19 infection and its course Retrospective 683 patients in a rheumatology department, 384 chronic HCQ users and 299 control patients, showing no mortality for HCQ users vs. 2 deaths in the control group, and significantly fewer cases forHCQ users.
risk of death, 82.1% lower, RR 0.18, _p_ = 0.19, treatment 0 of 385 (0.0%), control 2 of 299 (0.7%), continuity correction due to zeroevent.
risk of COVID-19 case, 93.7% lower, RR 0.06, _p_ < 0.001, treatment 2 of 395 (0.5%), control 24 of 299 (8.0%). Korkmaz et al., 6/1/2021, retrospective, Turkey, Middle East, preprint, 4 authors.Share Tweet
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Kamstrup et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.05.076 (Peer Reviewed) hosp., ↑44.0%, p=0.25 Hydroxychloroquine as a primary prophylactic agent against sars-cov-2 infection: a cohort study Details Retrospective HCQ users in Denmark, not showing a significant difference, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Authors appear unaware of research in the area, for ex.. 6/1 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Kamstrup et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.05.076 (Peer Reviewed) Hydroxychloroquine as a primary prophylactic agent against sars-cov-2 infection: a cohort study Retrospective HCQ users in Denmark, not showing a significant difference, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Authors appear unaware of research in the area, for example saying that "currently, no obvious connection exists between a known rheumatological disorder and the risk of contracting SARS-CoV-2". Many papers show that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, e.g., Ferri et al. show OR 4.42,
_p_<0.001 .
Supplementary data is not currently available. c19study.com/ferri.html risk of hospitalization, 44.0% higher, RR 1.44, _p_ = 0.25, treatment 5488, control 54846. risk of COVID-19 case, 10.0% lower, RR 0.90, _p_ = 0.23, treatment 188 of 5488 (3.4%), control 2040 of 54846 (3.7%), adjusted Cox proportional hazards regression. Kamstrup et al., 6/1/2021, retrospective, population-based cohort, Denmark, Europe, peer-reviewed, 21 authors.Share Tweet
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Smith et al., medRxiv, doi:10.1101/2021.05.28.21258012 (PeerReviewed)
death, ↓27.2%, p<0.0001 Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic Details Retrospective 255 mechanical ventilation patients in USA, showing that weight-adjusted HCQ+AZ improved survival by over 100%. QTc prolongation did not correlate with cumulative HCQ dose or HCQ serum level. Although authors mention immort.. 5/31 Details SourceLate treatment study Late treatment study Smith et al., medRxiv, doi:10.1101/2021.05.28.21258012 (Peer
Reviewed)
Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic Retrospective 255 mechanical ventilation patients in USA, showing that weight-adjusted HCQ+AZ improved survival by over 100%. QTc prolongation did not correlate with cumulative HCQ dose or HCQ serumlevel.
Although authors mention immortal time bias, full details on the timing of HCQ administration is not provided and this is not fully addressed. Survival curves indicate immortal time bias will significantly change results, although the observed benefit appears to exceed the potential bias. risk of death, 27.2% lower, RR 0.73, _p_ < 0.001, treatment 19 of 37 (51.4%), control 182 of 218 (83.5%), OR converted to RR, >3g HCQ and >1g AZ, multivariable cox proportional hazard regression. risk of death, 92.9% lower, RR 0.07, _p_ < 0.001, ≥80mg/kg HCQ and>1g AZ.
Smith et al., 5/31/2021, retrospective, USA, North America, peer-reviewed, 4 authors.Share Tweet
Submit Corrections or Comments5/27 Early
Million et al., Preprint (Preprint) death, ↓83.0%, p=0.0009 Early Treatment with Hydroxychloroquine and Azithromycin in 10,429 COVID-19 Outpatients: A Monocentric Retrospective Cohort Study Details Retrospective 10,429 outpatients in France, 8,315 treated with HCQ+AZ a median of 4 days from symptom onset, showing significantly lower mortality with treatment. 5/27 Details SourceEarly treatment study Early treatment study Million et al., Preprint (Preprint) Early Treatment with Hydroxychloroquine and Azithromycin in 10,429 COVID-19 Outpatients: A Monocentric Retrospective Cohort Study Retrospective 10,429 outpatients in France, 8,315 treated with HCQ+AZ a median of 4 days from symptom onset, showing significantly lower mortality with treatment. risk of death, 83.0% lower, RR 0.17, _p_ < 0.001, treatment 5 of 8315 (0.1%), control 11 of 2114 (0.5%), adjusted. Million et al., 5/27/2021, retrospective, France, Europe, preprint, 28 authors, dosage 200mg tid days 1-10.
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Submit Corrections or Comments5/17 PrEP
Syed et al., medRxiv, doi:10.1101/2021.05.17.21257012 (Preprint) symp. case, ↑59.7%, p=0.41 Pre-Exposure Prophylaxis with Various Doses of Hdroxychloroquine among high-risk COVID 19 Healthcare Personnel: CHEER randomizedcontrolled trial
Details Small PrEP RCT of low risk patients, showing no significant differences. Authors report that there was no hospitalization, ICU care or death from COVID-19, however table 3 shows events marked "requiring hospitalization". NCT0435.. 5/17 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Syed et al., medRxiv, doi:10.1101/2021.05.17.21257012 (Preprint) Pre-Exposure Prophylaxis with Various Doses of Hdroxychloroquine among high-risk COVID 19 Healthcare Personnel: CHEER randomized
controlled trial
Small PrEP RCT of low risk patients, showing no significant differences. Authors report that there was no hospitalization, ICU care or death from COVID-19, however table 3 shows events marked "requiring hospitalization". NCT04359537. risk of symptomatic case, 59.7% higher, RR 1.60, _p_ = 0.41, treatment 10 of 48 (20.8%), control 6 of 46 (13.0%), group 1. risk of symptomatic case, 110.5% higher, RR 2.10, _p_ = 0.13, treatment 14 of 51 (27.5%), control 6 of 46 (13.0%), group 2. risk of symptomatic case, 16.4% lower, RR 0.84, _p_ = 0.77, treatment 6 of 55 (10.9%), control 6 of 46 (13.0%), group 3. risk of COVID-19 case, 6.2% lower, RR 0.94, _p_ = 1.00, treatment 3 of 48 (6.2%), control 3 of 45 (6.7%), group 1. risk of COVID-19 case, 6.2% lower, RR 0.94, _p_ = 1.00, treatment 3 of 48 (6.2%), control 3 of 45 (6.7%), group 2. risk of COVID-19 case, 72.2% lower, RR 0.28, _p_ = 0.33, treatment 1 of 54 (1.9%), control 3 of 45 (6.7%), group 3. Syed et al., 5/17/2021, Randomized Controlled Trial, Pakistan, Middle East, preprint, 9 authors.Share Tweet
Submit Corrections or Comments5/16 PrEP
Rojas-Serrano et al., medRxiv, doi:10.1101/2021.05.14.21257059(Preprint)
symp. case, ↓82.0%, p=0.12 Hydroxychloroquine For Prophylaxis Of COVID-19 In Health Workers: A Randomized Clinical Trial Details Early terminated HCQ PrEP RCT with 62 HCQ and 65 placebo patients, showing 82% lower cases with treatment, _p_ = 0.12. NCT04318015. If the trial is continued and the same event rate is observed, statistical significance will be reachedaft..
5/16 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Rojas-Serrano et al., medRxiv, doi:10.1101/2021.05.14.21257059
(Preprint)
Hydroxychloroquine For Prophylaxis Of COVID-19 In Health Workers: A Randomized Clinical Trial Early terminated HCQ PrEP RCT with 62 HCQ and 65 placebo patients, showing 82% lower cases with treatment, _p_ = 0.12. NCT04318015. If the trial is continued and the same event rate is observed, statistical significance will be reached after adding about 16patients per arm.
risk of symptomatic case, 82.0% lower, RR 0.18, _p_ = 0.12, treatment 1 of 62 (1.6%), control 6 of 65 (9.2%), adjusted. Rojas-Serrano et al., 5/16/2021, Double Blind Randomized Controlled Trial, Mexico, North America, preprint, 8 authors.Share Tweet
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Drancourt et al., Viruses, doi:10.3390/v13050890 (Peer Reviewed) SARS-CoV-2 Persistent Viral Shedding in the Context of Hydroxychloroquine-Azithromycin Treatment Details Retrospective 3,737 patients in France, showing lower risk of persistent viral shedding with HCQ+AZtreatment.
5/12 Details SourceEarly treatment study Early treatment study Drancourt et al., Viruses, doi:10.3390/v13050890 (Peer Reviewed) SARS-CoV-2 Persistent Viral Shedding in the Context of Hydroxychloroquine-Azithromycin Treatment Retrospective 3,737 patients in France, showing lower risk of persistent viral shedding with HCQ+AZ treatment. Drancourt et al., 5/12/2021, peer-reviewed, 11 authors.
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Submit Corrections or Comments5/10 Late
Sammartino et al., PLOS One, doi:10.1371/journal.pone.0251262(Peer Reviewed)
death, ↑240.0%, p=0.002 Predictors for inpatient mortality during the first wave of the SARS-CoV-2 pandemic: A retrospective analysis Details Retrospective 1,108 hospitalized patients in New York showing significantly higher mortality with HCQ treatment. Time based confounding is very likely because HCQ became increasingly controversial and less used over the time covered (Mar.. 5/10 Details SourceLate treatment study Late treatment study Sammartino et al., PLOS One, doi:10.1371/journal.pone.0251262 (Peer
Reviewed)
Predictors for inpatient mortality during the first wave of the SARS-CoV-2 pandemic: A retrospective analysis Retrospective 1,108 hospitalized patients in New York showing significantly higher mortality with HCQ treatment. Time based confounding is very likely because HCQ became increasingly controversial and less used over the time covered (Mar - Jun 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved. Authors note that for every week or month later that a person was admitted, their risk of death dropped by 16% and 49%, respectively, yet they do not consider time based confounding. risk of death, 240.0% higher, RR 3.40, _p_ = 0.002, treatment 137, control 191, PSM, model 1a. Sammartino et al., 5/10/2021, retrospective, USA, North America, peer-reviewed, 7 authors.Share Tweet
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De Rosa et al., J. Clin. Med., doi:10.3390/jcm10091951 (PeerReviewed)
death, ↓35.0%, p=0.003 Risk Factors for Mortality in COVID-19 Hospitalized Patients in Piedmont, Italy: Results from the Multicenter, Regional, CORACLERegistry
Details Retrospective 1,538 hospitalized patients in Italy, showing only HCQ associated with reduced mortality. Authors analyze mortality amongst those that were alive at day 7 to avoid survival time bias due to drug recording requiring a minimum.. 5/1 Details SourceLate treatment study Late treatment study De Rosa et al., J. Clin. Med., doi:10.3390/jcm10091951 (Peer
Reviewed)
Risk Factors for Mortality in COVID-19 Hospitalized Patients in Piedmont, Italy: Results from the Multicenter, Regional, CORACLERegistry
Retrospective 1,538 hospitalized patients in Italy, showing only HCQ associated with reduced mortality. Authors analyze mortality amongst those that were alive at day 7 to avoid survival time bias due to drug recording requiring a minimum of 5 days treatment. risk of death, 35.0% lower, RR 0.65, _p_ = 0.003, treatment 118 of 731 (16.1%), control 80 of 280 (28.6%), adjusted, OR converted to RR, multivariate logistic regression, patients alive at day 7. risk of death, 36.0% lower, RR 0.64, treatment 207 of 1019 (20.3%), control 215 of 519 (41.4%), adjusted, OR converted to RR, multivariate logistic regression, all patients. De Rosa et al., 5/1/2021, retrospective, Italy, Europe, peer-reviewed, 20 authors.Share Tweet
Submit Corrections or Comments4/30 Late
Bosaeed et al., SSRN (Peer Reviewed) death, ↓3.7%, p=0.91 Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID-19 (FACCT): An Open-Label, Multicentre, Randomised, Controlled Trial Details RCT 254 very late stage (93% on oxygen, 17% in ICU at baseline) hospitalized patients in Saudi Arabia not showing significant differences with HCQ+favipiravir treatment. Only SaO2 < 94% patients were eligible, however the actual SaO2 of e.. 4/30 Details SourceLate treatment study Late treatment study Bosaeed et al., SSRN (Peer Reviewed) Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID-19 (FACCT): An Open-Label, Multicentre, Randomised, Controlled Trial RCT 254 very late stage (93% on oxygen, 17% in ICU at baseline) hospitalized patients in Saudi Arabia not showing significant differences with HCQ+favipiravir treatment. Only SaO2 < 94% patients were eligible, however the actual SaO2 of enrolled patients is not
provided.
risk of death, 3.7% lower, RR 0.96, _p_ = 0.91, treatment 14 of 125 (11.2%), control 15 of 129 (11.6%), 90 days. risk of death, 28.6% lower, RR 0.71, _p_ = 0.45, treatment 9 of 125 (7.2%), control 13 of 129 (10.1%), 28 days. risk of death, 65.1% higher, RR 1.65, _p_ = 0.45, treatment 8 of 125 (6.4%), control 5 of 129 (3.9%), 14 days. risk of mechanical ventilation, 8.4% higher, RR 1.08, _p_ = 0.78, treatment 21 of 125 (16.8%), control 20 of 129 (15.5%). risk of ICU admission, 31.0% higher, RR 1.31, _p_ = 0.24, treatment 33 of 125 (26.4%), control 26 of 129 (20.2%). recovery time, 28.6% higher, relative time 1.29, _p_ = 0.29, treatment 125, control 129. hospitalization time, 12.5% higher, relative time 1.12, _p_ = 0.42, treatment 125, control 129. risk of no virological cure, 2.6% lower, RR 0.97, _p_ = 0.75, treatment 100 of 125 (80.0%), control 106 of 129 (82.2%). Bosaeed et al., 4/30/2021, Randomized Controlled Trial, Saudi Arabia, Middle East, peer-reviewed, 30 authors.Share Tweet
Submit Corrections or Comments4/29 Late
Aghajani et al., Journal of Medical Virology, doi:10.1002/jmv.27053 (Peer Reviewed) death, ↓19.5%, p=0.09 Decreased In-Hospital Mortality Associated with Aspirin Administration in Hospitalized Patients Due to Severe COVID-19 Details Retrospective 991 hospitalized patients in Iran focusing on aspirin use but also showing results for HCQ, remdesivir, and favipiravir. 4/29 Details SourceLate treatment study Late treatment study Aghajani et al., Journal of Medical Virology, doi:10.1002/jmv.27053
(Peer Reviewed)
Decreased In-Hospital Mortality Associated with Aspirin Administration in Hospitalized Patients Due to Severe COVID-19 Retrospective 991 hospitalized patients in Iran focusing on aspirin use but also showing results for HCQ, remdesivir, and favipiravir. risk of death, 19.5% lower, RR 0.81, _p_ = 0.09, treatment 553, control 438, multivariate Cox proportional regression. Aghajani et al., 4/29/2021, retrospective, Iran, Middle East, peer-reviewed, 7 authors.Share Tweet
Submit Corrections or Comments4/28 Late
Kokturk et al., Respiratory Medicine, doi:10.1016/j.rmed.2021.106433 (Peer Reviewed) death, ↑3.8%, p=0.97 The predictors of COVID-19 mortality in a nationwide cohort ofTurkish patients
Details Retrospective 1,500 hospitalized late stage (median SaO2 87.7) patients in Turkey, showing no significant difference with HCQ treatment. 4/28 Details SourceLate treatment study Late treatment study Kokturk et al., Respiratory Medicine, doi:10.1016/j.rmed.2021.106433 (Peer Reviewed) The predictors of COVID-19 mortality in a nationwide cohort of
Turkish patients
Retrospective 1,500 hospitalized late stage (median SaO2 87.7) patients in Turkey, showing no significant difference with HCQtreatment.
risk of death, 3.8% higher, RR 1.04, _p_ = 0.97, treatment 62 of 1382 (4.5%), control 5 of 118 (4.2%), adjusted, OR converted to RR. Kokturk et al., 4/28/2021, retrospective, database analysis, Turkey, Europe, peer-reviewed, 68 authors.Share Tweet
Submit Corrections or Comments4/27 Late
Réa-Neto et al., Scientific Reports, doi:10.1038/s41598-021-88509-9 (Peer Reviewed) death, ↑57.0%, p=0.20 An open-label randomized controlled trial evaluating the efficacy of chloroquine/hydroxychloroquine in severe COVID-19 patients Details Early terminated very late stage (99% on oxygen, 81% in ICU, 18% on mechanical ventilation at baseline) RCT with 24 CQ patients, 29 HCQ, and 52 control patients, showing worse clinical outcomes with treatment. NCT04420247. 4/27 Details SourceLate treatment study Late treatment study Réa-Neto et al., Scientific Reports, doi:10.1038/s41598-021-88509-9 (Peer Reviewed) An open-label randomized controlled trial evaluating the efficacy of chloroquine/hydroxychloroquine in severe COVID-19 patients Early terminated very late stage (99% on oxygen, 81% in ICU, 18% on mechanical ventilation at baseline) RCT with 24 CQ patients, 29 HCQ, and 52 control patients, showing worse clinical outcomes with treatment. NCT04420247. risk of death, 57.0% higher, RR 1.57, _p_ = 0.20, treatment 16 of 53 (30.2%), control 10 of 52 (19.2%). risk of mechanical ventilation, 115.0% higher, RR 2.15, _p_ = 0.03. 9-point scale clinical status, 147.0% higher, OR 2.47, _p_ = 0.02. Réa-Neto et al., 4/27/2021, Randomized Controlled Trial, Brazil, South America, peer-reviewed, 6 authors.
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Submit Corrections or Comments4/26 Late
Mohandas et al., (Peer Reviewed) death, ↑81.0%, p=0.007 Clinical review of COVID-19 patients presenting to a quaternary care private hospital in South India: A retrospective study Details Retrospective 3,345 hospitalized patients in India, 11.5% treated with HCQ, showing unadjusted higher mortality with treatment. Confounding by indication and time based confounding (due to declining use over the period when overalltreatm..
4/26 Details SourceLate treatment study Late treatment study Mohandas et al., (Peer Reviewed) Clinical review of COVID-19 patients presenting to a quaternary care private hospital in South India: A retrospective study Retrospective 3,345 hospitalized patients in India, 11.5% treated with HCQ, showing unadjusted higher mortality with treatment. Confounding by indication and time based confounding (due to declining use over the period when overall treatment protocols improved dramatically) are likely. risk of death, 81.0% higher, RR 1.81, _p_ = 0.007, treatment 27 of 384 (7.0%), control 115 of 2961 (3.9%). Mohandas et al., 4/26/2021, retrospective, India, South Asia, peer-reviewed, 6 authors.
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Submit Corrections or Comments4/23 Late
Toya et al., SSRN (Preprint) A Cross-Country Analysis of the Determinants of COVID-19 Fatalities Details Country based analysis finding lower mortality with the use of HCQ. 4/23 Details SourceLate treatment study Late treatment study Toya et al., SSRN (Preprint) A Cross-Country Analysis of the Determinants of COVID-19 Fatalities Country based analysis finding lower mortality with the use of HCQ. Toya et al., 4/23/2021, preprint, 2 authors.
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Submit Corrections or Comments4/22 Late
Reis et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.6468 (Peer Reviewed) death, ↓66.0%, p=1.00 Effect of Early Treatment With Hydroxychloroquine or Lopinavir and Ritonavir on Risk of Hospitalization Among Patients With COVID-19 The TOGETHER Randomized Clinical Trial Details Early terminated RCT in Brazil showing lower mortality and hospitalization with HCQ, but not reaching statistical significance. Although the title includes "early treatment", treatment was relatively late, with most patients bei.. 4/22 Details SourceLate treatment study Late treatment study Reis et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.6468 (Peer Reviewed) Effect of Early Treatment With Hydroxychloroquine or Lopinavir and Ritonavir on Risk of Hospitalization Among Patients With COVID-19 The TOGETHER Randomized Clinical Trial Early terminated RCT in Brazil showing lower mortality and hospitalization with HCQ, but not reaching statistical significance. Although the title includes "early treatment", treatment was relatively late, with most patients being over 5 days from the onset of symptoms. Adverse events were lower in the HCQ group compared to
the control group.
The paper indicates the placebo was talc, however the trial protocol shows the "placebo" as vitamin C, for which there are 7 COVID-19 treatment studies as of April 2021 that collectively show significantefficacy.
risk of death, 66.0% lower, RR 0.34, _p_ = 1.00, treatment 0 of 214 (0.0%), control 1 of 227 (0.4%), continuity correction due to zeroevent.
risk of hospitalization, 24.0% lower, RR 0.76, _p_ = 0.57, treatment 8 of 214 (3.7%), control 11 of 227 (4.8%), ITT, Cox proportionalhazards.
risk of no virological cure, 4.1% lower, RR 0.96, _p_ < 0.001, treatment 97 of 185 (52.4%), control 102 of 179 (57.0%), adjusted, OR converted to RR, ITT, mixed-effect logistic model. Reis et al., 4/22/2021, Double Blind Randomized Controlled Trial, Brazil, South America, peer-reviewed, 18 authors, dosage 800mg day 1,400mg days 2-10.
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Submit Corrections or Comments4/15 PrEP
Alzahrani et al., Rheumatology International , doi:10.1007/s00296-021-04857-9 (Peer Reviewed) death, ↓58.8%, p=1.00 Clinical characteristics and outcome of COVID-19 in patients withrheumatic diseases
Details Retrospective 47 rheumatic disease patients not finding significant differences with HCQ. 4/15 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Alzahrani et al., Rheumatology International , doi:10.1007/s00296-021-04857-9 (Peer Reviewed) Clinical characteristics and outcome of COVID-19 in patients with
rheumatic diseases
Retrospective 47 rheumatic disease patients not finding significant differences with HCQ. risk of death, 58.8% lower, RR 0.41, _p_ = 1.00, treatment 0 of 14 (0.0%), control 1 of 33 (3.0%), continuity correction due to zeroevent.
risk of mechanical ventilation, 81.0% lower, RR 0.19, _p_ = 0.54, treatment 0 of 14 (0.0%), control 3 of 33 (9.1%), continuity correction due to zero event. risk of COVID-19 severe case, 32.7% lower, RR 0.67, _p_ = 0.70, treatment 2 of 14 (14.3%), control 7 of 33 (21.2%). Alzahrani et al., 4/15/2021, retrospective, Saudi Arabia, Middle East, peer-reviewed, 3 authors.Share Tweet
Submit Corrections or Comments4/15 PrEP
Alegiani et al., Rheumatology, doi:10.1093/rheumatology/keab348(Peer Reviewed)
death, ↑8.0%, p=0.64 Risk of COVID-19 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other conventional DMARDsin Italy
Details Retrospective database analysis case control study of rheumatic patients. When compared with other cDMARDs, HCQ users had significantly lower hospitalization, however there was no significant difference in mortality. Results differ signif.. 4/15 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Alegiani et al., Rheumatology, doi:10.1093/rheumatology/keab348
(Peer Reviewed)
Risk of COVID-19 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other conventional DMARDsin Italy
Retrospective database analysis case control study of rheumatic patients. When compared with other cDMARDs, HCQ users had significantly lower hospitalization, however there was no significant difference in mortality. Results differ significantly from previous studies, for example showing mortality OR 0.94 for patients with rheumatic disease and mortality OR 0.88 for patients with RA/SLE. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall. risk of death, 8.0% higher, RR 1.08, _p_ = 0.64, HCQ vs. other cDMARDs, RR approximated with OR. risk of hospitalization, 18.0% lower, RR 0.82, _p_ = 0.03, HCQ vs. other cDMARDs, RR approximated with OR. risk of death, 19.0% higher, RR 1.19, _p_ = 0.32, HCQ vs. MTX, RR approximated with OR. risk of hospitalization, 12.0% lower, RR 0.88, _p_ = 0.17, HCQ vs. MTX, RR approximated with OR. Alegiani et al., 4/15/2021, retrospective, case control, database analysis, Italy, Europe, peer-reviewed, 16 authors.Share Tweet
Submit Corrections or Comments4/14 PEP
Seet et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.04.035 (Peer Reviewed) severe case, ↓35.1%, p=0.14 Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial Details Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin .. 4/14 Details SourcePost Exposure Prophylaxis study Post Exposure Prophylaxis study Seet et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.04.035 (Peer Reviewed) Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C. Only 71.4% reported >70% adherence, limiting efficacy. QTc did not statistically significantly differ between baseline and follow-up readings (mean 379 vs 378ms, paired t-test _p_=0.387). Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters. There were no hospitalizations and no deaths. NCT04446104. risk of COVID-19 severe case, 35.1% lower, RR 0.65, _p_ = 0.14, treatment 29 of 432 (6.7%), control 64 of 619 (10.3%). risk of COVID-19 case, 32.0% lower, RR 0.68, _p_ = 0.009, treatment 212 of 432 (49.1%), control 433 of 619 (70.0%), adjusted, OR converted
to RR, model 6.
Seet et al., 4/14/2021, Cluster Randomized Controlled Trial, Singapore, Asia, peer-reviewed, 15 authors, dosage 400mg day 1, 200mg days 2-42, this trial compares with another treatment - results may be better when compared to placebo.Share Tweet
Submit Corrections or Comments4/6 Early
Mokhtari et al., International Immunopharmacology, doi:10.1016/j.intimp.2021.107636 (Peer Reviewed) death, ↓69.7%, p<0.0001 Clinical outcomes of patients with mild COVID-19 following treatment with hydroxychloroquine in an outpatient setting Details Retrospective 28,759 adult outpatients with mild COVID-19 in Iran, 7,295 treated with HCQ, showing significantly lower hospitalization and mortality with treatment. 4/6 Details SourceEarly treatment study Early treatment study Mokhtari et al., International Immunopharmacology, doi:10.1016/j.intimp.2021.107636 (Peer Reviewed) Clinical outcomes of patients with mild COVID-19 following treatment with hydroxychloroquine in an outpatient setting Retrospective 28,759 adult outpatients with mild COVID-19 in Iran, 7,295 treated with HCQ, showing significantly lower hospitalization and mortality with treatment. risk of death, 69.7% lower, RR 0.30, _p_ < 0.001, treatment 27 of 7295 (0.4%), control 287 of 21464 (1.3%), adjusted, OR converted to
RR.
risk of hospitalization, 35.3% lower, RR 0.65, _p_ < 0.001, treatment 523 of 7295 (7.2%), control 2382 of 21464 (11.1%), adjusted, ORconverted to RR.
Mokhtari et al., 4/6/2021, retrospective, Iran, Middle East, peer-reviewed, 11 authors, dosage 400mg bid day 1, 200mg bid days 2-5.Share Tweet
Submit Corrections or Comments4/5 Safety
Edington et al., European Journal of Internal Medicine, doi:10.1016/j.ejim.2021.03.028 (Peer Reviewed) (not included in thestudy count)
safety analysis
Safety of treatment with chloroquine and hydroxychloroquine: A ten-year systematic review and meta-analysis Details Safety analysis of CQ and HCQ covering 46 RCTs with 23,132 patients, showing no mortality attributed to CQ/HCQ. Authors conclude that the data reinforces that CQ and HCQ have a good safety profile though caution is advised when using high.. 4/5 Details SourceSafety
Safety
Edington et al., European Journal of Internal Medicine, doi:10.1016/j.ejim.2021.03.028 (Peer Reviewed) (not included in thestudy count)
Safety of treatment with chloroquine and hydroxychloroquine: A ten-year systematic review and meta-analysis Safety analysis of CQ and HCQ covering 46 RCTs with 23,132 patients, showing no mortality attributed to CQ/HCQ. Authors conclude that the data reinforces that CQ and HCQ have a good safety profile though caution is advised when using higher than usual doses in hospitalizedCOVID-19 patients.
Edington et al., 4/5/2021, peer-reviewed, 3 authors.Share Tweet
Submit Corrections or Comments3/31 Late
Alghamdi et al., Antibiotics, doi:10.3390/antibiotics10040365(Peer Reviewed)
death, ↑6.9%, p=0.88 Clinical Efficacy of Hydroxychloroquine in Patients with COVID-19: Findings from an Observational Comparative Study in Saudi Arabia Details Retrospective 775 hospitalized patients in Saudi Arabia showing no significant difference. There was no adjustment for severity or comorbidities. Confounding by indicationis likely.
3/31 Details SourceLate treatment study Late treatment study Alghamdi et al., Antibiotics, doi:10.3390/antibiotics10040365 (Peer
Reviewed)
Clinical Efficacy of Hydroxychloroquine in Patients with COVID-19: Findings from an Observational Comparative Study in Saudi Arabia Retrospective 775 hospitalized patients in Saudi Arabia showing no significant difference. There was no adjustment for severity or comorbidities. Confounding by indication is likely. risk of death, 6.9% higher, RR 1.07, _p_ = 0.88, treatment 44 of 568 (7.7%), control 15 of 207 (7.2%). Alghamdi et al., 3/31/2021, retrospective, Saudi Arabia, Middle East, peer-reviewed, 10 authors.Share Tweet
Submit Corrections or Comments3/26 Safety
Faruqui et al., Indian J. Med. Res., doi:10.4103/ijmr.IJMR_2294_20(Peer Reviewed)
safety analysis
Safety of hydroxychloroquine in healthcare workers for COVID-19prophylaxis
Details Retrospective 1303 health care workers finding that HCQ prophylaxis was well tolerated. 20% reported an adverse event, mostly gastrointestinal. 1.5% received treatment for adverse effects, with none requiring hospitalization. 3/26 Details SourceSafety
Safety
Faruqui et al., Indian J. Med. Res., doi:10.4103/ijmr.IJMR_2294_20(Peer Reviewed)
Safety of hydroxychloroquine in healthcare workers for COVID-19prophylaxis
Retrospective 1303 health care workers finding that HCQ prophylaxis was well tolerated. 20% reported an adverse event, mostly gastrointestinal. 1.5% received treatment for adverse effects, with none requiring hospitalization. Faruqui et al., 3/26/2021, peer-reviewed, 24 authors.Share Tweet
Submit Corrections or Comments3/24 PrEP
Dev et al., Transactions of The Royal Society of Tropical Medicine and Hygiene, doi:10.1093/trstmh/trab047 (Peer Reviewed) cases, ↓26.0%, p=0.003 Risk factors and frequency of COVID-19 among healthcare workers at a tertiary care centre in India: a case–control study Details Retrospective case control study of 3,100 healthcare workers in India showing lower cases with HCQ prophylaxis, and an inverse association between the number of HCQ doses taken and the risk of COVID-19 cases. Low risk population with no m.. 3/24 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Dev et al., Transactions of The Royal Society of Tropical Medicine and Hygiene, doi:10.1093/trstmh/trab047 (Peer Reviewed) Risk factors and frequency of COVID-19 among healthcare workers at a tertiary care centre in India: a case–control study Retrospective case control study of 3,100 healthcare workers in India showing lower cases with HCQ prophylaxis, and an inverse association between the number of HCQ doses taken and the risk of COVID-19 cases. Low risk population with no mortality and no severe cases. risk of COVID-19 case, 26.0% lower, RR 0.74, _p_ = 0.003, treatment 260, control 499, any number of HCQ doses vs. no HCQ prophylaxis. Dev et al., 3/24/2021, retrospective, India, South Asia, peer-reviewed, 5 authors.
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Submit Corrections or Comments3/23 Late
Barry et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.03.058 (Peer Reviewed) death, ↓98.9%, p=0.60 Clinical Characteristics and Outcomes of Hospitalized COVID-19 Patients in a MERS-CoV Referral Hospital during the Peak of thePandemic
Details 605 hospitalized patients in Saudi Arabia showing no mortality with HCQ (only 6 patients received HCQ). 3/23 Details SourceLate treatment study Late treatment study Barry et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.03.058 (Peer Reviewed) Clinical Characteristics and Outcomes of Hospitalized COVID-19 Patients in a MERS-CoV Referral Hospital during the Peak of the
Pandemic
605 hospitalized patients in Saudi Arabia showing no mortality with HCQ (only 6 patients received HCQ). risk of death, 98.9% lower, RR 0.01, _p_ = 0.60, treatment 0 of 6 (0.0%), control 91 of 599 (15.2%), continuity correction due to zeroevent.
Barry et al., 3/23/2021, retrospective, Saudi Arabia, Middle East, peer-reviewed, 14 authors.Share Tweet
Submit Corrections or Comments3/17 Late
Stewart et al., PLoS ONE, doi:10.1371/journal.pone.0248128 (PeerReviewed)
death, ↑18.0%, p=0.27 COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients Details Collection of seven retrospective database analyses in the USA, showing higher mortality with treatment (not statistically significant). Results contradict strong evidence from the RECOVERY/SOLIDARITY trials, suggesting substantial confo.. 3/17 Details SourceLate treatment study Late treatment study Stewart et al., PLoS ONE, doi:10.1371/journal.pone.0248128 (Peer
Reviewed)
COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients Collection of seven retrospective database analyses in the USA, showing higher mortality with treatment (not statisticallysignificant).
Results contradict strong evidence from the RECOVERY/SOLIDARITY trials, suggesting substantial confounding by indication. Time based confounding is very likely because HCQ became highly controversial and usage dramatically declined over the time covered, while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved. This study includes anyone PCR+ during or prior to their visit, and anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore some patients in the control groups may be asymptomatic with regards to SARS-CoV-2, but in the hospital foranother reason.
Authors do not mention the possibility of any of these likely confounding factors. risk of death, 18.0% higher, RR 1.18, _p_ = 0.27, treatment 90 of 429 (21.0%), control 141 of 737 (19.1%), adjusted, VA, HCQ+AZ. risk of death, 1.0% lower, RR 0.99, _p_ = 0.95, treatment 66 of 578 (11.4%), control 188 of 1243 (15.1%), adjusted, TriNetX, HCQ+AZ. risk of death, 129.9% higher, RR 2.30, _p_ < 0.001, treatment 32 of 108 (29.6%), control 33 of 256 (12.9%), Synapse, HCQ+AZ. risk of death, 9.0% higher, RR 1.09, _p_ = 0.65, treatment 212 of 1157 (18.3%), control 203 of 1101 (18.4%), adjusted, Health Catalyst,HCQ+AZ.
risk of death, 90.0% higher, RR 1.90, _p_ = 0.09, treatment 46 of 208 (22.1%), control 47 of 1334 (3.5%), adjusted, Dascena, HCQ+AZ. risk of death, 16.0% higher, RR 1.16, _p_ = 0.26, treatment 428 of 1711 (25.0%), control 123 of 688 (17.9%), adjusted, COTA/HMH, HCQ+AZ. risk of mechanical ventilation, 29.0% higher, RR 1.29, _p_ = 0.09, treatment 48 of 305 (15.7%), control 95 of 1302 (7.3%), adjusted,Aetion, HCQ.
Stewart et al., 3/17/2021, retrospective, USA, North America, peer-reviewed, 37 authors.Share Tweet
Submit Corrections or Comments3/17 In Vitro
Dang et al., bioRxiv, doi:10.1101/2021.03.16.435741 (Preprint) (InVitro)
_in vitro_
Structural basis of anti-SARS-CoV-2 activity of hydroxychloroquine: specific binding to NTD/CTD and disruption of LLPS of N protein Details Microscopy/spectroscopy study showing that HCQ binds to both N-terminal domain and C-terminal domain of SARS-CoV-2 nucleocapsid protein to inhibit their interactions with nucleic acids and disrupt NA-induced liquid-liquid phase separation.. 3/17 Details SourceIn Vitro
In Vitro
Dang et al., bioRxiv, doi:10.1101/2021.03.16.435741 (Preprint) (InVitro)
Structural basis of anti-SARS-CoV-2 activity of hydroxychloroquine: specific binding to NTD/CTD and disruption of LLPS of N protein Microscopy/spectroscopy study showing that HCQ binds to both N-terminal domain and C-terminal domain of SARS-CoV-2 nucleocapsidprotein to inhibit
their interactions with nucleic acids and disrupt NA-induced liquid-liquid phase separation essential for the viral life cycle including the package of gRNA and N protein into new virions. These results suggest that HCQ may achieve its anti-SARS-CoV-2 activity by interfering in several key steps of theviral life cycle.
Dang et al., 3/17/2021, preprint, 2 authors.Share Tweet
Submit Corrections or Comments3/12 Early
Roy et al., medRxiv, doi:10.1101/2021.03.08.21252883 (Preprint) recov. time, ↓2.4%, p=0.96 Outcome of Different Therapeutic Interventions in Mild COVID-19 Patients in a Single OPD Clinic of West Bengal: A Retrospective study Details Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and .. 3/12 Details SourceEarly treatment study Early treatment study Roy et al., medRxiv, doi:10.1101/2021.03.08.21252883 (Preprint) Outcome of Different Therapeutic Interventions in Mild COVID-19 Patients in a Single OPD Clinic of West Bengal: A Retrospective study Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and there was no significant difference between the groups. relative time to clinical response of wellbeing, 2.4% lower, relative time 0.98, _p_ = 0.96, treatment 14, control 15. Roy et al., 3/12/2021, retrospective, database analysis, India, South Asia, preprint, 5 authors, dosage not specified.
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Submit Corrections or Comments3/9 PrEP
Vivanco-Hidalgo et al., Eurosurveillance, doi:/10.2807/1560-7917.ES.2021.26.9.2001202 (Peer Reviewed) hosp., ↑46.0%, p=0.10 Incidence of COVID-19 in patients exposed to chloroquine and hydroxychloroquine: results from a population-based prospective cohort in Catalonia, Spain, 2020 Details Retrospective database analysis of chronic HCQ users and matched control patients, failing to match or adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 fo.. 3/9 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Vivanco-Hidalgo et al., Eurosurveillance, doi:/10.2807/1560-7917.ES.2021.26.9.2001202 (Peer Reviewed) Incidence of COVID-19 in patients exposed to chloroquine and hydroxychloroquine: results from a population-based prospective cohort in Catalonia, Spain, 2020 Retrospective database analysis of chronic HCQ users and matched control patients, failing to match or adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, _p_<0.001
.
c19study.com/ferri.html risk of hospitalization, 46.0% higher, RR 1.46, _p_ = 0.10, treatment 40 of 6746 (0.6%), control 50 of 13492 (0.4%), adjusted. risk of COVID-19 case, 8.0% higher, RR 1.08, _p_ = 0.50, treatment 97 of 6746 (1.4%), control 183 of 13492 (1.4%), adjusted. Vivanco-Hidalgo et al., 3/9/2021, retrospective, Spain, Europe, peer-reviewed, 8 authors.Share Tweet
Submit Corrections or Comments3/8 Late
Martin-Vicente et al., medRxiv, doi:10.1101/2021.03.08.21253121(Preprint)
death, ↓59.3%, p=0.41 Absent or insufficient anti-SARS-CoV-2 S antibodies at ICU admission are associated to higher viral loads in plasma, antigenemia and mortality in COVID-19 patients Details Retrospective 92 ICU patients with almost all treated with HCQ and only one non-HCQ treated patient that died, showing unadjusted non-statistically significant lower mortality with treatment. 3/8 Details SourceLate treatment study Late treatment study Martin-Vicente et al., medRxiv, doi:10.1101/2021.03.08.21253121
(Preprint)
Absent or insufficient anti-SARS-CoV-2 S antibodies at ICU admission are associated to higher viral loads in plasma, antigenemia and mortality in COVID-19 patients Retrospective 92 ICU patients with almost all treated with HCQ and only one non-HCQ treated patient that died, showing unadjusted non-statistically significant lower mortality with treatment. risk of death, 59.3% lower, RR 0.41, _p_ = 0.41, treatment 37 of 91 (40.7%), control 1 of 1 (100.0%). Martin-Vicente et al., 3/8/2021, retrospective, Spain, Europe, preprint, 38 authors.Share Tweet
Submit Corrections or Comments3/4 Late
Salvador et al., Cureus, doi:10.7759/cureus.13687 (Peer Reviewed) death, ↓32.9%, p=0.007 Clinical Features and Prognostic Factors of 245 Portuguese Patients Hospitalized With COVID-19 Details Prospective study of 245 hospitalized patients, 121 treated with HCQ, showing lower (non-statistically significant) mortality and higher ventilation at 30 days. Confounding by indication is likely. 3/4 Details SourceLate treatment study Late treatment study Salvador et al., Cureus, doi:10.7759/cureus.13687 (Peer Reviewed) Clinical Features and Prognostic Factors of 245 Portuguese Patients Hospitalized With COVID-19 Prospective study of 245 hospitalized patients, 121 treated with HCQ, showing lower (non-statistically significant) mortality and higher ventilation at 30 days. Confounding by indication is likely. risk of death, 32.9% lower, RR 0.67, _p_ = 0.007, treatment 28 of 121 (23.1%), control 58 of 124 (46.8%), OR converted to RR, multivariate. risk of mechanical ventilation, 447.8% higher, RR 5.48, _p_ = 0.003, treatment 32 of 121 (26.4%), control 12 of 124 (9.7%), OR converted to
RR, multivariate.
risk of combined intubation/death, 16.7% lower, RR 0.83, _p_ = 0.02, treatment 51 of 121 (42.1%), control 63 of 124 (50.8%), OR convertedto RR, univariate.
Salvador et al., 3/4/2021, prospective, Portugal, Europe, peer-reviewed, 10 authors.Share Tweet
Submit Corrections or Comments3/2 PrEP
Pham et al., Rheumatology Advances in Practice, 10.1093/rap/rkab014 (Peer Reviewed) death, ↓19.7%, p=0.77 Failure of chronic hydroxychloroquine in preventing severe complications of COVID-19 in patients with rheumatic diseases Details Tiny retrospective database analysis of hospitalized COVID-19 patients with rheumatologic disease containing 14 chronic HCQ and 28 control patients. Patients are very poorly matched. Bias against HCQ is clear in the abstract which mention.. 3/2 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Pham et al., Rheumatology Advances in Practice, 10.1093/rap/rkab014
(Peer Reviewed)
Failure of chronic hydroxychloroquine in preventing severe complications of COVID-19 in patients with rheumatic diseases Tiny retrospective database analysis of hospitalized COVID-19 patients with rheumatologic disease containing 14 chronic HCQ and 28 control patients. Patients are very poorly matched. Bias against HCQ is clear in the abstract which mentions differences favoring HCQ but ignores those favoring control (large differences in ethnicity, rheumatic conditions, hypertension, coronary artery disease, solid organ transplant recipients, immunosuppresive drugs). 61% of control patients also received HCQ. Adherence for chronic HCQ patients was not examined. Despite the very large differences between the groups, no adjustments are made. The study claims that HCQ did not prevent severe cases, but the study is among hospitalized patients, i.e., they already have cases severe enough for hospitalization - this study can not identify a protective effect of HCQ that reduces the probability of disease severe enough for hospitalization. risk of death, 19.7% lower, RR 0.80, _p_ = 0.77, treatment 2 of 14 (14.3%), control 5 of 28 (17.9%), OR converted to RR, univariate. risk of ICU admission, 35.5% higher, RR 1.35, _p_ = 0.61, treatment 4 of 14 (28.6%), control 6 of 28 (21.4%), OR converted to RR,univariate.
Pham et al., 3/2/2021, retrospective, USA, North America, peer-reviewed, 5 authors.Share Tweet
Submit Corrections or Comments2/28 Early
Thakar et al., Indian J. Med. Res., doi:10.4103/ijmr.IJMR_3665_20(Peer Reviewed)
Chloroquine nasal drops in asymptomatic & mild COVID-19: An exploratory randomized clinical trial Details Small RCT for CQ nasal drops suggesting efficacy in preventing infection, while no significant difference was seen for patients that already had mild COVID-19. 2/28 Details SourceEarly treatment study Early treatment study Thakar et al., Indian J. Med. Res., doi:10.4103/ijmr.IJMR_3665_20
(Peer Reviewed)
Chloroquine nasal drops in asymptomatic & mild COVID-19: An exploratory randomized clinical trial Small RCT for CQ nasal drops suggesting efficacy in preventing infection, while no significant difference was seen for patients that already had mild COVID-19. Thakar et al., 2/28/2021, peer-reviewed, 11 authors.Share Tweet
Submit Corrections or Comments2/28 PrEP
Bhandari et al., International Journal of Medicine and Public Health, doi:10.5530/ijmedph.2021.1.4 (Peer Reviewed) A Preventive Study on Hydroxychloroquine Prophylaxis against COVID-19 in Health Care Workers at a Tertiary Care Center in NorthIndia
Details Retrospective 4,239 healthcare workers using HCQ prophylaxis showing no mortality, 8 mild symptomatic cases, and 85 asymptomatic cases, with the cases occuring mostly in the firstweek.
2/28 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Bhandari et al., International Journal of Medicine and Public Health, doi:10.5530/ijmedph.2021.1.4 (Peer Reviewed) A Preventive Study on Hydroxychloroquine Prophylaxis against COVID-19 in Health Care Workers at a Tertiary Care Center in North
India
Retrospective 4,239 healthcare workers using HCQ prophylaxis showing no mortality, 8 mild symptomatic cases, and 85 asymptomatic cases, with the cases occuring mostly in the first week. Bhandari et al., 2/28/2021, India, South Asia, peer-reviewed, 10authors.
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Submit Corrections or Comments2/26 Early
Amaravadi et al., medRxiv, doi:10.1101/2021.02.22.21252228(Preprint)
no recov., ↓60.0%, p=0.13 Hydroxychloroquine for SARS-CoV-2 positive patients quarantined at home: The first interim analysis of a remotely conducted randomizedclinical trial
Details Tiny early-terminated 34 patient RCT for outpatient treatment showing faster recovery with treatment (not statistically significant). All patients recovered (3 control patients recovered after crossover to the treatment arm). There was no.. 2/26 Details SourceEarly treatment study Early treatment study Amaravadi et al., medRxiv, doi:10.1101/2021.02.22.21252228
(Preprint)
Hydroxychloroquine for SARS-CoV-2 positive patients quarantined at home: The first interim analysis of a remotely conducted randomizedclinical trial
Tiny early-terminated 34 patient RCT for outpatient treatment showing faster recovery with treatment (not statistically significant). All patients recovered (3 control patients recovered after crossover to the treatment arm). There was no mortality and only one hospitalization on day 0 before treatment. There were no severeadverse events.
risk of not reaching lowest symptom score at day 7 mid-recovery, 60.0% lower, RR 0.40, _p_ = 0.13, treatment 3 of 15 (20.0%), control 6of 12 (50.0%).
relative time to first occurrence of lowest symptom score, 42.9% lower, relative time 0.57, _p_ = 0.21, treatment 15, control 12. relative time to release from quarantine, 27.3% lower, relative time 0.73, _p_ = 0.28, treatment 16, control 13. Amaravadi et al., 2/26/2021, Double Blind Randomized Controlled Trial, USA, North America, preprint, 20 authors, dosage 400mg bid days1-14.
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Submit Corrections or Comments2/26 Late
Tanriverdi et al., Turkish Journal of Medical Sciences, doi:doi:10.3906/sag-2005-82 (Peer Reviewed) Hydroxychloroquine plus azithromycin and early hospital admission are beneficial in COVID-19 patients: Turkish experience with real-lifedata
Details Retrospective 83 hospitalized patients in Turkey confirming that earlier treatment is better, and showing that the addition of AZ to HCQ reduced hospitalization time. 2/26 Details SourceLate treatment study Late treatment study Tanriverdi et al., Turkish Journal of Medical Sciences, doi:doi:10.3906/sag-2005-82 (Peer Reviewed) Hydroxychloroquine plus azithromycin and early hospital admission are beneficial in COVID-19 patients: Turkish experience with real-life
data
Retrospective 83 hospitalized patients in Turkey confirming that earlier treatment is better, and showing that the addition of AZ to HCQ reduced hospitalization time. Tanriverdi et al., 2/26/2021, peer-reviewed, 8 authors.Share Tweet
Submit Corrections or Comments2/26 Early
Giraud-Gatineau et al., Research Square, doi:rs.3.rs-251817/v1(Preprint)
The Need for Early Management in Patients With COVID-19 Details Review of early treatment of COVID-19 at IHU Méditerranée Infection in France, including HCQ+AZ treatment, comparing outcomes to those for all of France. Age-standardized mortality was lower with early treatment for all periods of the epi.. 2/26 Details SourceEarly treatment study Early treatment study Giraud-Gatineau et al., Research Square, doi:rs.3.rs-251817/v1
(Preprint)
The Need for Early Management in Patients With COVID-19 Review of early treatment of COVID-19 at IHU Méditerranée Infection in France, including HCQ+AZ treatment, comparing outcomes to those for all of France. Age-standardized mortality was lower with early treatment for all periods of the epidemic. Authors recommend early treatment for all age groups. Giraud-Gatineau et al., 2/26/2021, preprint, 9 authors.Share Tweet
Submit Corrections or Comments2/23 Late
Gonzalez et al., medRxiv, doi:10.1101/2021.02.18.21252037 (PeerReviewed)
death, ↓62.6%, p=0.27 Efficacy and safety of Ivermectin and Hydroxychloroquine in patients with severe COVID-19. A randomized controlled trial Details RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high comorbidity hospitalized patients in Mexico with 33 HCQ and 37 control patients not finding significant differences. NCT04391127. 2/23 Details SourceLate treatment study Late treatment study Gonzalez et al., medRxiv, doi:10.1101/2021.02.18.21252037 (Peer
Reviewed)
Efficacy and safety of Ivermectin and Hydroxychloroquine in patients with severe COVID-19. A randomized controlled trial RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high comorbidity hospitalized patients in Mexico with 33 HCQ and 37 control patients not finding significant differences. NCT04391127. risk of death, 62.6% lower, RR 0.37, _p_ = 0.27, treatment 2 of 33 (6.1%), control 6 of 37 (16.2%). risk of respiratory deterioration or death, 25.3% lower, RR 0.75, _p_ = 0.57, treatment 6 of 33 (18.2%), control 9 of 37 (24.3%). risk of no hospital discharge, 12.1% higher, RR 1.12, _p_ = 1.00, treatment 3 of 33 (9.1%), control 3 of 37 (8.1%). Gonzalez et al., 2/23/2021, Double Blind Randomized Controlled Trial, Mexico, North America, peer-reviewed, mean age 53.8, 13 authors.Share Tweet
Submit Corrections or Comments2/20 PrEP
Bae et al., Viruses 2021, doi:10.3390/v13020329 (Peer Reviewed) cases, ↓30.3%, p=0.17 Recent Hydroxychloroquine Use Is Not Significantly Associated with Positive PCR Results for SARS-CoV-2: A Nationwide Observational Studyin South Korea
Details Retrospective database analysis of prior HCQ usage in South Korea, showing non-statistically significantly lower mortality and cases with treatment. 2/20 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Bae et al., Viruses 2021, doi:10.3390/v13020329 (Peer Reviewed) Recent Hydroxychloroquine Use Is Not Significantly Associated with Positive PCR Results for SARS-CoV-2: A Nationwide Observational Study
in South Korea
Retrospective database analysis of prior HCQ usage in South Korea, showing non-statistically significantly lower mortality and cases withtreatment.
risk of COVID-19 case, 30.3% lower, RR 0.70, _p_ = 0.17, treatment 16 of 743 (2.2%), control 91 of 2698 (3.4%), OR converted to RR, PSM. risk of COVID-19 case, 19.5% lower, RR 0.81, _p_ = 0.49, treatment 16 of 743 (2.2%), control 91 of 2698 (3.4%), OR converted to RR, PSM, adjusted for region. risk of COVID-19 case, 30.3% lower, RR 0.70, _p_ = 0.29, treatment 16 of 743 (2.2%), control 91 of 2698 (3.4%), OR converted to RR, PSM, adjusted for immunosuppresant use. risk of COVID-19 case, 40.2% lower, RR 0.60, _p_ = 0.08, OR converted to RR, PSM, HCQ >= 6 months. Bae et al., 2/20/2021, retrospective, South Korea, Asia, peer-reviewed, 8 authors.Share Tweet
Submit Corrections or Comments2/19 Late
Lamback et al., The Brazilian Journal of Infectious Diseases, doi:10.1016/j.bjid.2021.101549 (Peer Reviewed) death, ↓8.9%, p=0.83 Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19 Details Retrospective 193 hospitalized patients in Brazil not finding a significant difference with HCQ. The control group was composed of patients refusing HCQ or with contraindications. Time based confounding is very likely because HCQ became .. 2/19 Details SourceLate treatment study Late treatment study Lamback et al., The Brazilian Journal of Infectious Diseases, doi:10.1016/j.bjid.2021.101549 (Peer Reviewed) Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19 Retrospective 193 hospitalized patients in Brazil not finding a significant difference with HCQ. The control group was composed of patients refusing HCQ or with contraindications. Time based confounding is very likely because HCQ became more controversial in Brazil over the time covered (Mar - Jun 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients (those refusing HCQ) likely come later in the period when treatment protocols were greatly
improved.
The paper does not mention the word "confounding" or make anyadjustments.
risk of death, 8.9% lower, RR 0.91, _p_ = 0.83, treatment 11 of 101 (10.9%), control 11 of 92 (12.0%). risk of ICU admission, 19.9% higher, RR 1.20, _p_ = 0.61, treatment 25 of 101 (24.8%), control 19 of 92 (20.7%). hospitalization time, 12.5% lower, relative time 0.88, treatment 101,control 92.
Lamback et al., 2/19/2021, retrospective, Brazil, South America, peer-reviewed, 10 authors.Share Tweet
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Awad et al., American Journal of Health-System Pharmacy, doi:10.1093/ajhp/zxab056 (Peer Reviewed) death, ↑19.1%, p=0.60 Impact of hydroxychloroquine on disease progression and ICU admissions in patients with SARS-CoV-2 infection Details This paper has inconsistent values - the number of treatment and control patients differs in the text and Table 1, we have used treatment 188 and control 148. Retrospective 336 hospitalized patients in the USA showing higher mortality, IC.. 2/18 Details SourceLate treatment study Late treatment study Awad et al., American Journal of Health-System Pharmacy, doi:10.1093/ajhp/zxab056 (Peer Reviewed) Impact of hydroxychloroquine on disease progression and ICU admissions in patients with SARS-CoV-2 infection This paper has inconsistent values - the number of treatment and control patients differs in the text and Table 1, we have used treatment 188 and control 148. Retrospective 336 hospitalized patients in the USA showing higher mortality, ICU admission, and intubation with treatment. Confounding by indication is likely. Time varying confounding is also likely due to declining usage over the early period when overall treatment protocols were also improving dramatically. Authors and reviewers appear to be unfamiliar with
either of these.
risk of death, 19.1% higher, RR 1.19, _p_ = 0.60, treatment 56 of 188 (29.8%), control 37 of 148 (25.0%). risk of mechanical ventilation, 460.7% higher, RR 5.61, _p_ < 0.001, treatment 64 of 188 (34.0%), control 9 of 148 (6.1%), adjusted, ORconverted to RR.
risk of ICU admission, 463.4% higher, RR 5.63, _p_ < 0.001, treatment 67 of 188 (35.6%), control 9 of 148 (6.1%), adjusted, OR converted toRR.
Awad et al., 2/18/2021, retrospective, USA, North America, peer-reviewed, 4 authors.Share Tweet
Submit Corrections or Comments2/11 Late
Lora-Tamayo et al., J. Infection, doi:10.1016/j.jinf.2021.02.011(Peer Reviewed)
death, ↓50.5%, p<0.0001 Early Lopinavir/ritonavir does not reduce mortality in COVID-19 patients: results of a large multicenter study Details Lopinavir/ritonavir retrospective study also showing univariate results for HCQ, with significantlylower mortality.
2/11 Details SourceLate treatment study Late treatment study Lora-Tamayo et al., J. Infection, doi:10.1016/j.jinf.2021.02.011
(Peer Reviewed)
Early Lopinavir/ritonavir does not reduce mortality in COVID-19 patients: results of a large multicenter study Lopinavir/ritonavir retrospective study also showing univariate results for HCQ, with significantly lower mortality. risk of death, 50.5% lower, RR 0.50, _p_ < 0.001, treatment 7192, control 1361, OR converted to RR, univariate. Lora-Tamayo et al., 2/11/2021, retrospective, Spain, Europe, peer-reviewed, 10 authors.Share Tweet
Submit Corrections or Comments2/10 Early, Late
Desai et al., J. Clinical Medicine, doi:10.3390/jcm10040686 (PeerReviewed)
The Use of Antiviral Agents against SARS-CoV-2: Ineffective or Time and Age Dependent Result? A Retrospective, Observational Study among COVID-19 Older Adults Details Retrospective 143 COVID-19 hospitalized patients >65yo, showing adjusted OR for antiviral treatment starting within 6 days of 0.44 , _p_ = 0.02, compared to treatmentstarted later.
2/10 Details SourceEarly, Late
Early, Late
Desai et al., J. Clinical Medicine, doi:10.3390/jcm10040686 (PeerReviewed)
The Use of Antiviral Agents against SARS-CoV-2: Ineffective or Time and Age Dependent Result? A Retrospective, Observational Study among COVID-19 Older Adults Retrospective 143 COVID-19 hospitalized patients >65yo, showing adjusted OR for antiviral treatment starting within 6 days of 0.44 , _p_ = 0.02, compared to treatment started later. Desai et al., 2/10/2021, peer-reviewed, 9 authors.Share Tweet
Submit Corrections or Comments2/9 Meta
Lounnas e al., Archives of Microbiology & Immunology, doi: (Peer Reviewed) (meta analysis - not included in study count)meta-analysis
Revisiting a Meta-analysis Shows that Hydroxychloroquine with Azithromycin may be Efficient in Covid-19 patients Details Analysis of the Fiolet meta analysis and correction of bias evaluation, showing HCQ RR 0.45 , and HCQ+AZ RR 0.34 . 2/9 Details SourceMeta
Meta
Lounnas e al., Archives of Microbiology & Immunology, doi: (Peer Reviewed) (meta analysis - not included in study count) Revisiting a Meta-analysis Shows that Hydroxychloroquine with Azithromycin may be Efficient in Covid-19 patients Analysis of the Fiolet meta analysis and correction of bias evaluation, showing HCQ RR 0.45 , and HCQ+AZ RR 0.34.
Lounnas et al., 2/9/2021, peer-reviewed, 4 authors.Share Tweet
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Purwati et al., Biochemistry Research International, doi:10.1155/2021/6685921 (Peer Reviewed) viral+, ↓66.3%, p<0.0001 A Randomized, Double-Blind, Multicenter Clinical Study Comparing the Efficacy and Safety of a Drug Combination of Lopinavir/Ritonavir-Azithromycin, Lopinavir/Ritonavir-Doxycycline, and Azithromycin-Hydroxychloroquine for Patients Diagnosed with Mild to Moderate COVID-19 Infections Details RCT 754 patients comparing HCQ+AZ along with other treatment groups using lopinavir/ritonavir and doxycycline to a control group taking AZ, finding significantly faster viral clearance with all treatment groups. (The labels in Figure 2 ap.. 2/9 Details SourceLate treatment study Late treatment study Purwati et al., Biochemistry Research International, doi:10.1155/2021/6685921 (Peer Reviewed) A Randomized, Double-Blind, Multicenter Clinical Study Comparing the Efficacy and Safety of a Drug Combination of Lopinavir/Ritonavir-Azithromycin, Lopinavir/Ritonavir-Doxycycline, and Azithromycin-Hydroxychloroquine for Patients Diagnosed with Mild to Moderate COVID-19 Infections RCT 754 patients comparing HCQ+AZ along with other treatment groups using lopinavir/ritonavir and doxycycline to a control group taking AZ, finding significantly faster viral clearance with all treatment groups. (The labels in Figure 2 appear to be reversed). risk of no virological cure, 66.3% lower, RR 0.34, _p_ < 0.001, treatment 38 of 121 (31.4%), control 111 of 119 (93.3%). Purwati et al., 2/9/2021, Double Blind Randomized Controlled Trial, Indonesia, Asia, peer-reviewed, 12 authors.
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Submit Corrections or Comments2/5 PrEP
Fitzgerald et al., medRxiv, doi:10.1101/2021.02.03.21251069(Preprint)
cases, ↓8.5%, p=0.52 Risk Factors for Infection and Health Impacts of the COVID-19 Pandemic in People with Autoimmune Diseases Details Retrospective 4666 people with autoimmune or inflammatory conditions, showing HCQ adjusted risk of COVID-19 OR 0.91 . Results are not adjusted for the significantly different risk of COVID-19 depending on the type andseverity ..
2/5 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Fitzgerald et al., medRxiv, doi:10.1101/2021.02.03.21251069
(Preprint)
Risk Factors for Infection and Health Impacts of the COVID-19 Pandemic in People with Autoimmune Diseases Retrospective 4666 people with autoimmune or inflammatory conditions, showing HCQ adjusted risk of COVID-19 OR 0.91 . Results are not adjusted for the significantly different risk of COVID-19 depending on the type and severity of autoimmune or inflammatorycondition.
risk of COVID-19 case, 8.5% lower, RR 0.91, _p_ = 0.52, treatment 65 of 1072 (6.1%), control 200 of 3594 (5.6%), adjusted, OR converted toRR.
Fitzgerald et al., 2/5/2021, retrospective, USA, North America, preprint, 34 authors.Share Tweet
Submit Corrections or Comments2/5 Late
Hernandez-Cardenas et al., medRxiv, doi:10.1101/2021.02.01.21250371 (Preprint) death, ↓12.0%, p=0.66 Hydroxychloroquine for the treatment of severe respiratory infection by COVID-19: a randomized controlled trial Details Very late stage RCT with 214 patients, mean SpO2 65%, 162 on mechanical ventilation, showing no signficant difference in mortality. Patients not intubated at baseline show greater improvement, HR 0.43 . Table 4 showsdifferen..
2/5 Details SourceLate treatment study Late treatment study Hernandez-Cardenas et al., medRxiv, doi:10.1101/2021.02.01.21250371
(Preprint)
Hydroxychloroquine for the treatment of severe respiratory infection by COVID-19: a randomized controlled trial Very late stage RCT with 214 patients, mean SpO2 65%, 162 on mechanical ventilation, showing no signficant difference in mortality. Patients not intubated at baseline show greater improvement, HR 0.43.
Table 4 shows different results to the abstract - table 4 adjusted HR 0.80 , abstract HR 0.88 . There was no significant difference in severe adverse events. risk of death, 12.0% lower, RR 0.88, _p_ = 0.66, treatment 106,control 108.
risk of death, 57.0% lower, RR 0.43, _p_ = 0.29, subgroup not intubated at baseline. Hernandez-Cardenas et al., 2/5/2021, Randomized Controlled Trial, Mexico, North America, preprint, 6 authors.Share Tweet
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Ouedraogo et al., Revue des Maladies Respiratoires, doi:10.1016/j.rmr.2021.02.001 (Peer Reviewed) death, ↓33.0%, p=0.38 Factors associated with the occurrence of acute respiratory distress and death in patients with COVID-19 in Burkina Faso Details Retrospective 456 patients in Burkina Faso showing lower risk of ARDS (_p_=0.001) and mortality (_p_=0.38)with HCQ.
2/5 Details SourceLate treatment study Late treatment study Ouedraogo et al., Revue des Maladies Respiratoires, doi:10.1016/j.rmr.2021.02.001 (Peer Reviewed) Factors associated with the occurrence of acute respiratory distress and death in patients with COVID-19 in Burkina Faso Retrospective 456 patients in Burkina Faso showing lower risk of ARDS (_p_=0.001) and mortality (_p_=0.38) with HCQ. risk of death, 33.0% lower, RR 0.67, _p_ = 0.38, treatment 397, control 59, multivariate. risk of ARDS, 68.0% lower, RR 0.32, _p_ = 0.001, treatment 397, control 59, multivariate. Ouedraogo et al., 2/5/2021, retrospective, Burkina Faso, Africa, peer-reviewed, 14 authors.
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Submit Corrections or Comments2/1 Review
Alexander et al., medRxiv, doi:10.1101/2021.01.28.21250706 (Review) (Preprint) (not included in the study count)review
Early Multidrug Outpatient Treatment of SARS-CoV-2 Infection (COVID-19) and Reduced Mortality Among Nursing Home Residents Details Review of studies on treatment of COVID-19 for nursing home residents, concluding that there is a large >60% mortality risk reduction associated with multidrug treatment using two or more intracellular anti-infectives (HCQ and either AZM .. 2/1 Details SourceReview
Review
Alexander et al., medRxiv, doi:10.1101/2021.01.28.21250706 (Review) (Preprint) (not included in the study count) Early Multidrug Outpatient Treatment of SARS-CoV-2 Infection (COVID-19) and Reduced Mortality Among Nursing Home Residents Review of studies on treatment of COVID-19 for nursing home residents, concluding that there is a large >60% mortality risk reduction associated with multidrug treatment using two or more intracellular anti-infectives (HCQ and either AZM or DOXY) combined with other agents including corticosteroids, anti-thrombotics, and nutraceuticals. Authors note there is also recent focus on ivermectin and favorable evidence for bromhexine. Alexander et al., 2/1/2021, preprint, 11 authors.Share Tweet
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Ubaldo et al., Critical Care Research and Practice, 10.1155/2021/7510306 (Peer Reviewed) death, ↓18.4%, p=0.64 COVID-19: A Single-Center ICU Experience of the First Wave in thePhilippines
Details Retrospective ICU patients in the Philippines showing unadjusted HCQ RR 0.82, _p_ = 0.64. 2/1 Details SourceLate treatment study Late treatment study Ubaldo et al., Critical Care Research and Practice, 10.1155/2021/7510306 (Peer Reviewed) COVID-19: A Single-Center ICU Experience of the First Wave in the
Philippines
Retrospective ICU patients in the Philippines showing unadjusted HCQ RR 0.82, _p_ = 0.64. risk of death, 18.4% lower, RR 0.82, _p_ = 0.64, treatment 17 of 25 (68.0%), control 5 of 6 (83.3%), COVID-19 positive patients. Ubaldo et al., 2/1/2021, retrospective, Philippines, Asia, peer-reviewed, 3 authors.Share Tweet
Submit Corrections or Comments1/31 PrEP
Naderi et al., Immunopathologia Persa, doi:10.34172/ipp.2021.29(Peer Reviewed)
Prophylactic effects of hydroxychloroquine on the incidence of COVID-19 in patients with rheumatic arthritis: an observational cohortstudy
Details Prospective observational study of 215 RA patients treated with HCQ showing 9 cases, 1 hospitalization (without ICU/intubation), and no mortality. 1/31 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Naderi et al., Immunopathologia Persa, doi:10.34172/ipp.2021.29
(Peer Reviewed)
Prophylactic effects of hydroxychloroquine on the incidence of COVID-19 in patients with rheumatic arthritis: an observational cohortstudy
Prospective observational study of 215 RA patients treated with HCQ showing 9 cases, 1 hospitalization (without ICU/intubation), and nomortality.
Naderi et al., 1/31/2021, peer-reviewed, 7 authors.Share Tweet
Submit Corrections or Comments1/31 Late
Roig et al., Revista Espanola de Quimioterapia, doi:10.37201/req/130.2020 (Peer Reviewed) death, ↓15.6%, p=0.76 Clinical and pharmacological data in COVID-19 hospitalized nonagenarian patients Details Retrospective 79 hospitalized nonagenarian patients showing unadjusted HCQ mortality RR 0.84, _p_ = 0.76. 1/31 Details SourceLate treatment study Late treatment study Roig et al., Revista Espanola de Quimioterapia, doi:10.37201/req/130.2020 (Peer Reviewed) Clinical and pharmacological data in COVID-19 hospitalized nonagenarian patients Retrospective 79 hospitalized nonagenarian patients showing unadjusted HCQ mortality RR 0.84, _p_ = 0.76. risk of death, 15.6% lower, RR 0.84, _p_ = 0.76, treatment 33 of 67 (49.3%), control 7 of 12 (58.3%). Roig et al., 1/31/2021, retrospective, Spain, Europe, peer-reviewed,
6 authors.
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Submit Corrections or Comments1/27 PrEP
Trefond et al., SSRM, doi:10.2139/ssrn.3754815 (Preprint) death, ↑16.6%, p=0.80 Impact of hydroxychloroquine used as DMARD on SARS CoV-2 tests andCOVID-19 evolution
Details Retrospective 71 chronic HCQ patients compared with 191 matched controls, analyzing only those with a highly suspected or confirmed diagnosis of COVID-19. No significant difference was found in outcomes, however matching failed with extre.. 1/27 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Trefond et al., SSRM, doi:10.2139/ssrn.3754815 (Preprint) Impact of hydroxychloroquine used as DMARD on SARS CoV-2 tests and
COVID-19 evolution
Retrospective 71 chronic HCQ patients compared with 191 matched controls, analyzing only those with a highly suspected or confirmed diagnosis of COVID-19. No significant difference was found in outcomes, however matching failed with extreme confounding - 77.5% of HCQ patients with systemic autoimmune diseases vs. 21.5% of controlpatients.
Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42,_p_<0.001 .
c19study.com/ferri.html risk of death, 16.6% higher, RR 1.17, _p_ = 0.80, treatment 4 of 68 (5.9%), control 12 of 183 (6.6%), adjusted, OR converted to RR. risk of combined death/ICU, 78.2% higher, RR 1.78, _p_ = 0.21, treatment 8 of 71 (11.3%), control 18 of 191 (9.4%), adjusted, ORconverted to RR.
risk of hospitalization, 44.9% higher, RR 1.45, _p_ = 0.12, treatment 24 of 71 (33.8%), control 53 of 191 (27.7%), adjusted, OR converted toRR.
Trefond et al., 1/27/2021, retrospective, France, Europe, preprint,21 authors.
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Submit Corrections or Comments1/26 Safety
Eftekhar et al., medRxiv, doi:10.1101/2021.01.16.21249941(Preprint)
safety analysis
Hydroxychloroquine and azithromycin: As a double edge sword forCOVID-19?
Details Retrospective 172 hospitalized patients, 83% treated and HCQ+AZ and 17% with HCQ, not finding a significant difference in QTc prolongation, but recommending careful monitoring for the use of HCQ+AZ; especially in males, patients withhigh..
1/26 Details SourceSafety
Safety
Eftekhar et al., medRxiv, doi:10.1101/2021.01.16.21249941(Preprint)
Hydroxychloroquine and azithromycin: As a double edge sword forCOVID-19?
Retrospective 172 hospitalized patients, 83% treated and HCQ+AZ and 17% with HCQ, not finding a significant difference in QTc prolongation, but recommending careful monitoring for the use of HCQ+AZ; especially in males, patients with high-risk Tisdale score, and in patients who have baseline QTc interval ≥ 450 milliseconds. Eftekhar et al., 1/26/2021, preprint, 6 authors.Share Tweet
Submit Corrections or Comments1/25 Early
Dabbous et al., Archives of Virology, doi:10.1007/s00705-021-04956-9 (Peer Reviewed) Efficacy of favipiravir in COVID-19 treatment: a multi-centerrandomized study
Details RCT with 44 favipiravir patients and 48 CQ patients, showing non-statistically significant lower mortality, ventilation, and hospitalization time with favipiravir. 1/25 Details SourceEarly treatment study Early treatment study Dabbous et al., Archives of Virology, doi:10.1007/s00705-021-04956-9 (Peer Reviewed) Efficacy of favipiravir in COVID-19 treatment: a multi-center
randomized study
RCT with 44 favipiravir patients and 48 CQ patients, showing non-statistically significant lower mortality, ventilation, and hospitalization time with favipiravir. Dabbous et al., 1/25/2021, peer-reviewed, 10 authors.Share Tweet
Submit Corrections or Comments1/25 In Silico
Hussein et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129979 (Peer Reviewed) Molecular Docking Identification for the efficacy of Some Zinc Complexes with Chloroquine and Hydroxychloroquine against Main Protease of COVID-19 Details Molecular dynamics analysis recommending Zn (CQ) Cl2(H2O) and Zn (HCQ) Cl2(H2O) as potential inhibitors for COVID-19 Mpro. Zn (HCQ) Cl2(H2O) exhibited a strong binding to the main protease receptor, forming eight hydrogen bonds. 1/25 Details SourceIn Silico
In Silico
Hussein et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129979 (Peer Reviewed) Molecular Docking Identification for the efficacy of Some Zinc Complexes with Chloroquine and Hydroxychloroquine against Main Protease of COVID-19 Molecular dynamics analysis recommending Zn (CQ) Cl2(H2O) and Zn (HCQ) Cl2(H2O) as potential inhibitors for COVID-19 Mpro. Zn (HCQ) Cl2(H2O) exhibited a strong binding to the main protease receptor, forming eight hydrogen bonds. Hussein et al., 1/25/2021, peer-reviewed, 2 authors.Share Tweet
Submit Corrections or Comments1/24 Early
Zelenko, Z., Preprint (Preprint) Nebulized Hydroxychloroquine for COVID-19 Treatment: 80x Improvement in Breathing Details Report on the use of nebulized HCQ showing much more rapid improvement compared to tablets, with 95% of patients experiencing improved breathing within 1 hour. Author notes that the effectiveness of HCQ is time and dose dependent, with a .. 1/24 Details SourceEarly treatment study Early treatment study Zelenko, Z., Preprint (Preprint) Nebulized Hydroxychloroquine for COVID-19 Treatment: 80x Improvement in Breathing Report on the use of nebulized HCQ showing much more rapid improvement compared to tablets, with 95% of patients experiencing improved breathing within 1 hour. Author notes that the effectiveness of HCQ is time and dose dependent, with a primary issue being the time it takes for a therapeutic dosage to reach the lungs, and that treatment with tablets may take an average of 80 hours to achieve significant clinical improvement. Author notes that it may take 3-7 days to achieve optimal alveolar concentrations with tablets, whereas nebulized HCQ administered as microdroplets directly to the lungs achieves optimal alveolar concentration in approximately one hour and is associated with faster clinical improvement, reduction in pulmonary complications, and a reduction in medical costs. Zelenko et al., 1/24/2021, preprint, 1 author.
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Submit Corrections or Comments1/23 PrEP
Cifuentes et al., Medicina Clínica (English Edition), doi:10.1016/j.medcle.2020.10.012 (Peer Reviewed) Incidence of COVID-19 in patients under chronic treatment withhydroxychloroquine
Details Retrospective 3,817 chronic HCQ patients showing 4.4% COVID-19 positive rate, 1.3% severe. There is no comparison with a control group. Authors note that there was a 3.6% incidence among 2,032,863 patients in one of the regions (Castilla .. 1/23 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Cifuentes et al., Medicina Clínica (English Edition), doi:10.1016/j.medcle.2020.10.012 (Peer Reviewed) Incidence of COVID-19 in patients under chronic treatment with
hydroxychloroquine
Retrospective 3,817 chronic HCQ patients showing 4.4% COVID-19 positive rate, 1.3% severe. There is no comparison with a control group. Authors note that there was a 3.6% incidence among 2,032,863 patients in one of the regions (Castilla La Mancha), however they provide no information on this group - it is expected that the mostly systemic autoimmune disease patients in the treatment group are older on average. Additonally, other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, _p_<0.001 . c19study.com/ferri.html Cifuentes et al., 1/23/2021, peer-reviewed, 18 authors.Share Tweet
Submit Corrections or Comments1/18 Late
Li et al., Science China Life Sciences, doi:10.1007/s11427-020-1871-4 (Peer Reviewed) no disch., ↓50.0%, p=0.08 Evaluation of the efficacy and safety of hydroxychloroquine in comparison with chloroquine in moderate and severe patients withCOVID-19
Details Small RCT comparing HCQ and CQ in China with 88 very late stage (17.6 days from onset to hospitalization and ~10 days to randomization) patients. The primary clinical outcomes (TTCR and TTCI) were not significantly different. Authors note.. 1/18 Details SourceLate treatment study Late treatment study Li et al., Science China Life Sciences, doi:10.1007/s11427-020-1871-4 (Peer Reviewed) Evaluation of the efficacy and safety of hydroxychloroquine in comparison with chloroquine in moderate and severe patients with
COVID-19
Small RCT comparing HCQ and CQ in China with 88 very late stage (17.6 days from onset to hospitalization and ~10 days to randomization) patients. The primary clinical outcomes (TTCR and TTCI) were not significantly different. Authors note that HCQ may have more promising efficacy in immune system modulation, indicated by ferritin reduction in the moderate cases and improvement of CT scores and lymphocyte counts in the severe cases. HCQ and CQ were well tolerated. Authors also compare RCT patients to a matched sample of non-RCT patients in the same hospital, showing shorter time to discharge with CQ/HCQ, but not statistically significant due to the small size. risk of no hospital discharge, 50.0% lower, RR 0.50, _p_ = 0.08, treatment 14, control 14, RCT patients vs. matched sample of non-treated patients. Li et al., 1/18/2021, retrospective, China, Asia, peer-reviewed, 21authors.
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Submit Corrections or Comments1/12 Late
Li et al., Research Square, doi:10.21203/rs.3.rs-119202/v1(Preprint)
viral- time, ↑40.0%, p=0.06 Treatment of COVID-19 patients with hydroxychloroquine or chloroquine: A retrospective analysis Details Small retrospective database analysis of 37 late stage patients hospitalized in an intensive care center in China, not finding a significant difference in viral shedding. Pateints were all in serious condition. There was only one death ho.. 1/12 Details SourceLate treatment study Late treatment study Li et al., Research Square, doi:10.21203/rs.3.rs-119202/v1
(Preprint)
Treatment of COVID-19 patients with hydroxychloroquine or chloroquine: A retrospective analysis Small retrospective database analysis of 37 late stage patients hospitalized in an intensive care center in China, not finding a significant difference in viral shedding. Pateints were all in serious condition. There was only one death however the group is not specified. Confounding by indication is likely. time to viral-, 40.0% higher, relative time 1.40, _p_ = 0.06, treatment 18, control 19. Li et al., 1/12/2021, retrospective, database analysis, China, Asia, preprint, 5 authors.Share Tweet
Submit Corrections or Comments1/10 PrEP
Rangel et al., Journal of the American Academy of Dermatology, doi:10.1016/j.jaad.2020.10.098 (Peer Reviewed) death, ↓25.1%, p=0.77 Chronic Hydroxychloroquine Therapy and COVID-19 Outcomes: A Retrospective Case-Control Analysis Details Retrospective 50 COVID-19 patients that take chronic HCQ, compared to a matched sample of patients not taking chronic HCQ, showing lower mortality and ICU admission, and shorter hospitalization for HCQ patients, but not statistically sign.. 1/10 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Rangel et al., Journal of the American Academy of Dermatology, doi:10.1016/j.jaad.2020.10.098 (Peer Reviewed) Chronic Hydroxychloroquine Therapy and COVID-19 Outcomes: A Retrospective Case-Control Analysis Retrospective 50 COVID-19 patients that take chronic HCQ, compared to a matched sample of patients not taking chronic HCQ, showing lower mortality and ICU admission, and shorter hospitalization for HCQ patients, but not statistically significant due to the small number of
events.
The actual benefit for HCQ could be much larger. The study does not address the risk of being sick enough to visit the hospital. HCQ users are likely systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42,_p_<0.001 .
c19study.com/ferri.html risk of death, 25.1% lower, RR 0.75, _p_ = 0.77, treatment 4 of 50 (8.0%), control 11 of 103 (10.7%), from all patients. risk of hospitalization, 22.2% lower, RR 0.78, _p_ = 0.29, treatment 17 of 50 (34.0%), control 45 of 103 (43.7%). hospitalization time, 41.2% lower, relative time 0.59, _p_ = 0.12, treatment 21, control 54. Rangel et al., 1/10/2021, retrospective, USA, North America, peer-reviewed, 5 authors.Share Tweet
Submit Corrections or Comments1/8 Late
Yegerov et al., medRxiv, doi:10.1101/2021.01.06.20249091 (PeerReviewed)
death, ↓95.3%, p=1.00 Epidemiological and Clinical Characteristics, and Virologic Features of COVID-19 Patients in Kazakhstan: a Nation-Wide, Retrospective, Cohort Study Details Retrospective 1,072 hospitalized patients in Kazakhstan showing no mortality for HCQ treated patients, however only 23 patients received treatment - this result is not statistically significant. 1/8 Details SourceLate treatment study Late treatment study Yegerov et al., medRxiv, doi:10.1101/2021.01.06.20249091 (Peer
Reviewed)
Epidemiological and Clinical Characteristics, and Virologic Features of COVID-19 Patients in Kazakhstan: a Nation-Wide, Retrospective, Cohort Study Retrospective 1,072 hospitalized patients in Kazakhstan showing no mortality for HCQ treated patients, however only 23 patients received treatment - this result is not statistically significant. risk of death, 95.3% lower, RR 0.05, _p_ = 1.00, treatment 0 of 23 (0.0%), control 20 of 1049 (1.9%), continuity correction due to zeroevent.
Yegerov et al., 1/8/2021, retrospective, Kazakhstan, Asia, peer-reviewed, 8 authors.Share Tweet
Submit Corrections or Comments1/7 In Silico
Baildya et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129891 (Peer Reviewed) (not included inthe study count)
Inhibitory capacity of Chloroquine against SARS-COV-2 by effective binding with Angiotensin converting enzyme-2 receptor: An insight from molecular docking and MD-simulation studies Details Molecular docking study of 16 drugs showing CQ had the highest binding affinity with ACE2, and molecular dynamics study of the docked CQ-ACE2 structure. Authors conclude that CQ binds reasonably strongly with ACE2 and the stable ACE2-CQ m.. 1/7 Details SourceIn Silico
In Silico
Baildya et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129891 (Peer Reviewed) (not included inthe study count)
Inhibitory capacity of Chloroquine against SARS-COV-2 by effective binding with Angiotensin converting enzyme-2 receptor: An insight from molecular docking and MD-simulation studies Molecular docking study of 16 drugs showing CQ had the highest binding affinity with ACE2, and molecular dynamics study of the docked CQ-ACE2 structure. Authors conclude that CQ binds reasonably strongly with ACE2 and the stable ACE2-CQ may prevent further binding of ACE2 with the SARS-CoV-2 spike protein. Baildya et al., 1/7/2021, peer-reviewed, 3 authors.Share Tweet
Submit Corrections or Comments1/6 Theory
Noureddine et al., Journal of King Saud University - Science, doi:10.1016/j.jksus.2020.101334 (Peer Reviewed) (Theory)theory
Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: molecular docking and DFT calculations Details _In silico_ analysis of hydroxychloroquine and hydroxychloroquine sulfate predicting that hydroxychloroquine sulfate is more stable and effective for COVID-19. 1/6 Details SourceTheory
Theory
Noureddine et al., Journal of King Saud University - Science, doi:10.1016/j.jksus.2020.101334 (Peer Reviewed) (Theory) Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: molecular docking and DFT calculations _In silico_ analysis of hydroxychloroquine and hydroxychloroquine sulfate predicting that hydroxychloroquine sulfate is more stable and effective for COVID-19. Noureddine et al., 1/6/2021, peer-reviewed, 5 authors.Share Tweet
Submit Corrections or Comments1/4 Safety
Gautret et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106236 (Peer Reviewed) (not included inthe study count)
safety analysis
Safety profile of hydroxychloroquine and azithromycin combined treatment in COVID-19 patients Details Report on the safety of HCQ+AZ with 3,737 COVID-19 patients. 138 had contraindications and treatment was discontinued in 12 cases due to QTc prolongation. There were no cases of torsade de pointe or sudden death. 1/4 Details SourceSafety
Safety
Gautret et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106236 (Peer Reviewed) (not included inthe study count)
Safety profile of hydroxychloroquine and azithromycin combined treatment in COVID-19 patients Report on the safety of HCQ+AZ with 3,737 COVID-19 patients. 138 had contraindications and treatment was discontinued in 12 cases due to QTc prolongation. There were no cases of torsade de pointe or suddendeath.
Gautret et al., 1/4/2021, peer-reviewed, 4 authors.Share Tweet
Submit Corrections or Comments1/2 Late
Sarfaraz et al., medRxiv, doi:10.1101/2020.12.28.20248920(Preprint)
death, ↑45.0%, p=0.07 Determinants of in-hospital mortality in COVID-19; a prospective cohort study from Pakistan Details Retrospective 186 hospitalized patients in Pakistan showing unadjusted HCQ mortality RR 1.45, _p_ = 0.07. Confounding by indication is likely. 1/2 Details SourceLate treatment study Late treatment study Sarfaraz et al., medRxiv, doi:10.1101/2020.12.28.20248920
(Preprint)
Determinants of in-hospital mortality in COVID-19; a prospective cohort study from Pakistan Retrospective 186 hospitalized patients in Pakistan showing unadjusted HCQ mortality RR 1.45, _p_ = 0.07. Confounding by indication is likely. risk of death, 45.0% higher, RR 1.45, _p_ = 0.07, treatment 40 of 94 (42.6%), control 27 of 92 (29.3%). Sarfaraz et al., 1/2/2021, retrospective, Pakistan, South Asia, preprint, 7 authors.Share Tweet
Submit Corrections or Comments1/1 Late
Lotfy et al., Turk. Thorac. J., doi:10.5152/TurkThoracJ.2021.20180(Peer Reviewed)
death, ↑24.8%, p=0.76 Use of Hydroxychloroquine in Patients with COVID-19: A Retrospective Observational Study Details Retrospective 202 patients in Saudi Arabia not showing significant differences with treatment. No information is provided on how patients were selected for treatment, there may be significant confounding by indication. Time varyingconfou..
1/1 Details SourceLate treatment study Late treatment study Lotfy et al., Turk. Thorac. J., doi:10.5152/TurkThoracJ.2021.20180
(Peer Reviewed)
Use of Hydroxychloroquine in Patients with COVID-19: A Retrospective Observational Study Retrospective 202 patients in Saudi Arabia not showing significant differences with treatment. No information is provided on how patients were selected for treatment, there may be significant confounding by indication. Time varying confounding is also likely as HCQ became controversial during the period studied, therefore HCQ use was likely more frequent toward the beginning of the period, a time when overall treatment protocols were significantly worse. risk of death, 24.8% higher, RR 1.25, _p_ = 0.76, treatment 6 of 99 (6.1%), control 5 of 103 (4.9%). risk of mechanical ventilation, 41.2% higher, RR 1.41, _p_ = 0.34, treatment 19 of 99 (19.2%), control 14 of 103 (13.6%). risk of ICU admission, 16.5% higher, RR 1.17, _p_ = 0.53, treatment 28 of 99 (28.3%), control 25 of 103 (24.3%). Lotfy et al., 1/1/2021, retrospective, Saudi Arabia, Middle East, peer-reviewed, mean age 55.0, 3 authors.Share Tweet
Submit Corrections or Comments1/1 Late
Sands et al., International Journal of Infectious Diseases, doi:/10.1016/j.ijid.2020.12.060 (Peer Reviewed) death, ↑69.9%, p=0.01 No clinical benefit in mortality associated with hydroxychloroquine treatment in patients with COVID-19 Details Retrospective database analysis of 1,669 patients in the US showing OR 1.81, _p_ = 0.01. Confounding by indication is likely. COVID-19 was determined via PCR+ results, therefore authors include patients asymptomatic for COVID-19, but int..
1/1 Details SourceLate treatment study Late treatment study Sands et al., International Journal of Infectious Diseases, doi:/10.1016/j.ijid.2020.12.060 (Peer Reviewed) No clinical benefit in mortality associated with hydroxychloroquine treatment in patients with COVID-19 Retrospective database analysis of 1,669 patients in the US showing OR 1.81, _p_ = 0.01. Confounding by indication is likely. COVID-19 was determined via PCR+ results, therefore authors include patients asymptomatic for COVID-19, but in the hospital for other reasons. While authors adjust for severity, the method used is very poor. 93.5% of patients are classified as "mild", which is patients with no documented care in a critical care unit within 8 hours of admission. Therefore almost all patients are in the same category, and those in a different category may be due to symptoms unrelated to COVID-19. Lower bias toward male patients in the control group also agrees with the hypothesis that the control group is made up of more people that were in hospital for another reason. Since the analysis covers the initial period of the pandemic in the USA, it is likely that HCQ was used more often earlier in the analysis period when treatment protocols were considerably worse. It's unclear why the analysis only considers patients up to April 27, when the manuscript was submitted in October. For other issues see . ijidonline.com/article/S1201-9712(21)00165-X/pdf risk of death, 69.9% higher, RR 1.70, _p_ = 0.01, treatment 101 of 973 (10.4%), control 56 of 696 (8.0%), OR converted to RR. Sands et al., 1/1/2021, retrospective, database analysis, USA, North America, peer-reviewed, 10 authors.
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Submit Corrections or Comments12/31 Review
Matada et al., Bioorganic & Medicinal Chemistry, doi:10.1016/j.bmc.2020.115973 (Review) (Peer Reviewed)review
A comprehensive review on the biological interest of quinoline andits derivatives
Details Review of quinolone and derivatives, natural and drug sources, and biological activity. 12/31 Details SourceReview
Review
Matada et al., Bioorganic & Medicinal Chemistry, doi:10.1016/j.bmc.2020.115973 (Review) (Peer Reviewed) A comprehensive review on the biological interest of quinoline andits derivatives
Review of quinolone and derivatives, natural and drug sources, and biological activity. Matada et al., 12/31/2020, peer-reviewed, 3 authors.Share Tweet
Submit Corrections or Comments12/31 Late
Psevdos et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa439.721 (Peer Reviewed) death, ↑63.5%, p=0.52 Corona Virus Disease-19 (COVID-19) in a Veterans Affairs Hospital at Suffolk County, Long Island, New York Details Retrospective 67 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was su.. 12/31 Details SourceLate treatment study Late treatment study Psevdos et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa439.721 (Peer Reviewed) Corona Virus Disease-19 (COVID-19) in a Veterans Affairs Hospital at Suffolk County, Long Island, New York Retrospective 67 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was suspended during the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse. risk of death, 63.5% higher, RR 1.63, _p_ = 0.52, treatment 17 of 52 (32.7%), control 3 of 15 (20.0%). Psevdos et al., 12/31/2020, retrospective, USA, North America, peer-reviewed, 3 authors.
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Submit Corrections or Comments12/31 Late
Texeira et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa439.560 (Peer Reviewed) death, ↑79.3%, p=0.10 Characteristics and outcomes of COVID-19 patients admitted to a regional health system in the southeast Details Retrospective 161 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and wass..
12/31 Details SourceLate treatment study Late treatment study Texeira et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa439.560 (Peer Reviewed) Characteristics and outcomes of COVID-19 patients admitted to a regional health system in the southeast Retrospective 161 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was suspended towards the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse. risk of death, 79.3% higher, RR 1.79, _p_ = 0.10, treatment 17 of 65 (26.2%), control 14 of 96 (14.6%). Texeira et al., 12/31/2020, retrospective, USA, North America, peer-reviewed, 6 authors.
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Submit Corrections or Comments12/31 Late
Vernaz et al., Swiss Medical Weekly, doi:10.4414/smw.2020.20446(Peer Reviewed)
death, ↓15.3%, p=0.71 Early experimental COVID-19 therapies: associations with length of hospital stay, mortality and related costs Details Retrospective 840 hospitalized patients in Switzerland showing non-statistically significant lower mortality with HCQ but significantly longer hospitalization times. Confounding by indication is likely. PSM fails to adjust for severity wi.. 12/31 Details SourceLate treatment study Late treatment study Vernaz et al., Swiss Medical Weekly, doi:10.4414/smw.2020.20446
(Peer Reviewed)
Early experimental COVID-19 therapies: associations with length of hospital stay, mortality and related costs Retrospective 840 hospitalized patients in Switzerland showing non-statistically significant lower mortality with HCQ but significantly longer hospitalization times. Confounding by indication is likely. PSM fails to adjust for severity with a 16% higher mNEWS score for HCQ vs. SOC in the matched cohort. Time varying confounding is likely. HCQ became controversial and was suspended towards the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse. Authors note: "overall, there was an indication bias, with the reason of prescription being associated with the outcome of interest. Indeed, patients with more severe COVID-19 were more likely to receive experimental therapies." risk of death, 15.3% lower, RR 0.85, _p_ = 0.71, treatment 12 of 93 (12.9%), control 16 of 105 (15.2%), HCQ vs. SOC. hospitalization time, 49.0% higher, relative time 1.49, _p_ = 0.002, treatment 93, control 105, HCQ vs. SOC. Vernaz et al., 12/31/2020, retrospective, Switzerland, Europe, peer-reviewed, 15 authors.Share Tweet
Submit Corrections or Comments12/30 Review
McCullough et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.264 (Review) (Peer Reviewed) (not includedin the study count)
review
Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19) Details Review urging early treatment of COVID-19 with sequential multidrug treatment that has been shown to be safe and effective. Proposed treatment includes zinc, vitamin D & C, quercetin, and depending on age, comorbidities, and symptoms may .. 12/30 Details SourceReview
Review
McCullough et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.264 (Review) (Peer Reviewed) (not includedin the study count)
Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19) Review urging early treatment of COVID-19 with sequential multidrug treatment that has been shown to be safe and effective. Proposed treatment includes zinc, vitamin D & C, quercetin, and depending on age, comorbidities, and symptoms may include >=2 of HCQ, ivermectin, favipiravir; AZM/DOXY; corticosteroids; colchicine; bamlanivimab; aspirin; LMWH; and supplemental oxygen. McCullough et al., 12/30/2020, peer-reviewed, 58 authors.Share Tweet
Submit Corrections or Comments12/30 Early
Procter et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.260 (Peer Reviewed) Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection Details Retrospective 922 outpatients, with 320 treated early due to age>50 or comorbidities, showing 2.2% hospitalization and 0.3% death, which authors note is considerably lower than reported in other studies in their region. At least two ofz..
12/30 Details SourceEarly treatment study Early treatment study Procter et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.260 (Peer Reviewed) Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection Retrospective 922 outpatients, with 320 treated early due to age>50 or comorbidities, showing 2.2% hospitalization and 0.3% death, which authors note is considerably lower than reported in other studies in
their region.
At least two of zinc, HCQ, and ivermectin were used, along with one antibiotic, and budesonide and/or dexamethasone. Procter et al., 12/30/2020, peer-reviewed, 6 authors.Share Tweet
Submit Corrections or Comments12/29 Late
Güner et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2020.12.017 (Peer Reviewed) ICU, ↓77.3%, p=0.16 Comparing ICU Admission Rates of Mild/Moderate COVID-19 Patients Treated with Hydroxychloroquine, Favipiravir, and Hydroxychloroquineplus Favipiravir
Details Retrospective 824 hospitalized patients in Turkey showing lower ICU admission for HCQ vs. favipiravir. 12/29 Details SourceLate treatment study Late treatment study Güner et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2020.12.017 (Peer Reviewed) Comparing ICU Admission Rates of Mild/Moderate COVID-19 Patients Treated with Hydroxychloroquine, Favipiravir, and Hydroxychloroquine
plus Favipiravir
Retrospective 824 hospitalized patients in Turkey showing lower ICU admission for HCQ vs. favipiravir. risk of ICU admission, 77.3% lower, RR 0.23, _p_ = 0.16, treatment 604, control 100, IPTW multivariate analysis. Güner et al., 12/29/2020, retrospective, Turkey, Middle East, peer-reviewed, 23 authors.Share Tweet
Submit Corrections or Comments12/28 PrEP
Cordtz et al., Rheumatology, doi:10.1093/rheumatology/keaa897(Peer Reviewed)
hosp., ↓24.0%, p=0.67 Incidence and severeness of COVID-19 hospitalisation in patients with inflammatory rheumatic disease: a nationwide cohort study fromDenmark
Details Retrospective 58,052 rheumatic disease patients in Denmark showing that RA patients have a higher risk of COVID-19 hospitalization in general. HCQ treated patients show lower risk, although this is not statistically significant with only .. 12/28 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Cordtz et al., Rheumatology, doi:10.1093/rheumatology/keaa897 (Peer
Reviewed)
Incidence and severeness of COVID-19 hospitalisation in patients with inflammatory rheumatic disease: a nationwide cohort study fromDenmark
Retrospective 58,052 rheumatic disease patients in Denmark showing that RA patients have a higher risk of COVID-19 hospitalization in general. HCQ treated patients show lower risk, although this is not statistically significant with only 3 hospitalizations for HCQ treatedpatients.
HR 0.76 time-dependent exposure model HR 0.45 time-fixed exposure model risk of hospitalization, 24.0% lower, RR 0.76, _p_ = 0.67, treatment 3 of 2722 (0.1%), control 38 of 26718 (0.1%), adjusted, time-dependentexposure model.
risk of hospitalization, 55.0% lower, RR 0.45, _p_ = 0.28, treatment 3 of 2722 (0.1%), control 38 of 26718 (0.1%), adjusted, time-fixedexposure model.
Cordtz et al., 12/28/2020, retrospective, population-based cohort, Denmark, Europe, peer-reviewed, 10 authors.Share Tweet
Submit Corrections or Comments12/24 Late
Chari et al., Blood, doi:10.1182/blood.2020008150 (Peer Reviewed) death, ↓33.1%, p=0.17 Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set Details Retrospective multiple myeloma patients showing lower mortality with HCQ treatment, unadjusted RR 0.67, _p_ = 0.17 (data is in the supplementary material). 12/24 Details SourceLate treatment study Late treatment study Chari et al., Blood, doi:10.1182/blood.2020008150 (Peer Reviewed) Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set Retrospective multiple myeloma patients showing lower mortality with HCQ treatment, unadjusted RR 0.67, _p_ = 0.17 (data is in the supplementary material). risk of death, 33.1% lower, RR 0.67, _p_ = 0.17, treatment 8 of 29 (27.6%), control 195 of 473 (41.2%). Chari et al., 12/24/2020, retrospective, multiple countries, multiple regions, peer-reviewed, median age 69.0, 25 authors.
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Submit Corrections or Comments12/23 Early
Su et al., BioScience Trends, doi:10.5582/bst.2020.03340 (PeerReviewed)
progression, ↓84.9%, p=0.006 Efficacy of early hydroxychloroquine treatment in preventing COVID-19 pneumonia aggravation, the experience from Shanghai, China Details 85% lower disease progression with early use of HCQ. Retrospective 616 patients in China showing adjusted progression HR 0.15, _p_ = 0.006. 12/23 Details SourceEarly treatment study Early treatment study Su et al., BioScience Trends, doi:10.5582/bst.2020.03340 (Peer
Reviewed)
Efficacy of early hydroxychloroquine treatment in preventing COVID-19 pneumonia aggravation, the experience from Shanghai, China 85% lower disease progression with early use of HCQ. Retrospective 616 patients in China showing adjusted progression HR 0.15, _p_ =0.006.
risk of disease progression, 84.9% lower, RR 0.15, _p_ = 0.006, treatment 261, control 355, adjusted, binary logistic regression. improvement time, 24.0% lower, relative time 0.76, _p_ = 0.02, treatment 261, control 355, adjusted, Cox proportional hazardsregression.
Su et al., 12/23/2020, retrospective, China, Asia, peer-reviewed, 9 authors, dosage 400mg days 1-10, 400mg daily for 10-14 days.Share Tweet
Submit Corrections or Comments12/23 Late
Taccone et al., The Lancet Regional Health - Europe, doi:10.1016/j.lanepe.2020.100019 (Peer Reviewed) death, ↓24.7%, p=0.0004 The role of organizational characteristics on the outcome of COVID-19 patients admitted to the ICU in Belgium Details Retrospective 1,747 ICU patients in Belgium showing lower mortality with HCQ, multivariate mixed effects analysis HCQ aOR 0.64 . 12/23 Details SourceLate treatment study Late treatment study Taccone et al., The Lancet Regional Health - Europe, doi:10.1016/j.lanepe.2020.100019 (Peer Reviewed) The role of organizational characteristics on the outcome of COVID-19 patients admitted to the ICU in Belgium Retrospective 1,747 ICU patients in Belgium showing lower mortality with HCQ, multivariate mixed effects analysis HCQ aOR 0.64
.
risk of death, 24.7% lower, RR 0.75, _p_ < 0.001, treatment 449 of 1308 (34.3%), control 183 of 439 (41.7%), OR converted to RR. Taccone et al., 12/23/2020, retrospective, Belgium, Europe, peer-reviewed, 10 authors.Share Tweet
Submit Corrections or Comments12/22 Late
Cangiano et al., Aging, doi:10.18632/aging.202307 (Peer Reviewed) death, ↓73.4%, p=0.03 Mortality in an Italian nursing home during COVID-19 pandemic: correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests Details 73% lower mortality with HCQ. Analysis of 98 PCR+ nursing home residents in Italy, mean age 90, showing HCQ mortality RR 0.27, _p_ = 0.03. Subject to confounding by contraindication. The paper provides the p value for regression butnot the..
12/22 Details SourceLate treatment study Late treatment study Cangiano et al., Aging, doi:10.18632/aging.202307 (Peer Reviewed) Mortality in an Italian nursing home during COVID-19 pandemic: correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests 73% lower mortality with HCQ. Analysis of 98 PCR+ nursing home residents in Italy, mean age 90, showing HCQ mortality RR 0.27, _p_ = 0.03. Subject to confounding by contraindication. The paper provides the p value for regression but not the effect size. risk of death, 73.4% lower, RR 0.27, _p_ = 0.03, treatment 5 of 33 (15.2%), control 37 of 65 (56.9%). Cangiano et al., 12/22/2020, retrospective, Italy, Europe, peer-reviewed, 14 authors.
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Submit Corrections or Comments12/19 PrEP
Huh et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.12.041 (Peer Reviewed) progression, ↑251.0%, p=0.11 Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea Details Retrospective database analysis with 17 existing users of HCQ and 5 severe cases, showing no significant difference for cases and higher risk for severe cases. However, HCQ users are likely systemic autoimmune disease patients and autho.. 12/19 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Huh et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.12.041 (Peer Reviewed) Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea Retrospective database analysis with 17 existing users of HCQ and 5 severe cases, showing no significant difference for cases and higher risk for severe cases. However, HCQ users are likely systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, _p_<0.001 . c19study.com/ferri.html risk of disease progression, 251.0% higher, RR 3.51, _p_ = 0.11, treatment 5 of 8 (62.5%), control 873 of 2797 (31.2%), adjusted. risk of COVID-19 case, 6.0% lower, RR 0.94, _p_ = 0.82, treatment 17 of 122 (13.9%), control 7324 of 36600 (20.0%), adjusted. Huh et al., 12/19/2020, retrospective, database analysis, South Korea, Asia, peer-reviewed, 8 authors.
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Submit Corrections or Comments12/18 Late
Matangila et al., PLoS ONE, doi:10.1371/journal.pone.0244272 (PeerReviewed)
death, ↓54.9%, p=0.21 Clinical characteristics of COVID-19 patients hospitalized at Clinique Ngaliema, a public hospital in Kinshasa, in the Democratic Republic of Congo: A retrospective cohort study Details 55% lower death with HCQ+AZ. Retrospective 160 hospitalized patients in the Democratic Republic of Congo, 92% receiving HCQ+AZ, showing adjusted OR 0.24 . 12/18 Details SourceLate treatment study Late treatment study Matangila et al., PLoS ONE, doi:10.1371/journal.pone.0244272 (Peer
Reviewed)
Clinical characteristics of COVID-19 patients hospitalized at Clinique Ngaliema, a public hospital in Kinshasa, in the Democratic Republic of Congo: A retrospective cohort study 55% lower death with HCQ+AZ. Retrospective 160 hospitalized patients in the Democratic Republic of Congo, 92% receiving HCQ+AZ, showingadjusted OR 0.24 .
risk of death, 54.9% lower, RR 0.45, _p_ = 0.21, treatment 25 of 147 (17.0%), control 8 of 13 (61.5%), adjusted, OR converted to RR. Matangila et al., 12/18/2020, retrospective, DR Congo, Africa, peer-reviewed, median age 54.0, 12 authors.Share Tweet
Submit Corrections or Comments12/16 Late
Signes-Costa et al., Archivos de Bronconeumología, doi:10.1016/j.arbres.2020.11.012 (Peer Reviewed) death, ↓47.0%, p=0.0005 Prevalence and 30-day mortality in hospitalized patients with COVID-19 and prior lung diseases Details 47% lower mortality with HCQ/CQ. Retrospective 1,271 patients with lung disease in Canada, China, Cuba, Ecuador, Germany, Italy and Spain, 83% treated with HCQ/CQ. Multivariable Cox regression HCQ/CQ mortality hazard ratio HR 0.53,_p_ < 0..
12/16 Details SourceLate treatment study Late treatment study Signes-Costa et al., Archivos de Bronconeumología, doi:10.1016/j.arbres.2020.11.012 (Peer Reviewed) Prevalence and 30-day mortality in hospitalized patients with COVID-19 and prior lung diseases 47% lower mortality with HCQ/CQ. Retrospective 1,271 patients with lung disease in Canada, China, Cuba, Ecuador, Germany, Italy and Spain, 83% treated with HCQ/CQ. Multivariable Cox regression HCQ/CQ mortality hazard ratio HR 0.53,
_p_ < 0.001.
risk of death, 47.0% lower, RR 0.53, _p_ < 0.001, treatment 4854, control 993, adjusted. Signes-Costa et al., 12/16/2020, retrospective, Spain, Canada, China, Cuba, Ecuador, Germany, Italy, Europe, Asia, Caribbean, North America, South America, peer-reviewed, 28 authors.Share Tweet
Submit Corrections or Comments12/16 PrEP
Gönenli et al., Research Square, doi:0.21203/rs.3.rs-107937/v1(Preprint)
progression, ↓29.7%, p=0.77 Prophylactic use of Hydroxychloroquine among Physicians working inPandemic Hospitals
Details Small prophylaxis survey showing lower, but not statistically significant, progression to pneumonia (3 of 148 HCQ, 12 of 416 control), RR 0.70, _p_ = 0.77. There was a higher incidence of cases with HCQ, OR 1.19, _p_ = 0.58, which may be due .. 12/16 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Gönenli et al., Research Square, doi:0.21203/rs.3.rs-107937/v1
(Preprint)
Prophylactic use of Hydroxychloroquine among Physicians working inPandemic Hospitals
Small prophylaxis survey showing lower, but not statistically significant, progression to pneumonia (3 of 148 HCQ, 12 of 416 control), RR 0.70, _p_ = 0.77. There was a higher incidence of cases with HCQ, OR 1.19, _p_ = 0.58, which may be due to survey bias, treatment self-selection, and inconsistent regimens. Improvement on severity may be related to the much higher HCQ concentration in lung tissue, and also reflect that binary PCR does not distinguish replication-competence. Details of the pneumonia numbers for treatment/control are from the author. risk of pneumonia, 29.7% lower, RR 0.70, _p_ = 0.77, treatment 3 of 148 (2.0%), control 12 of 416 (2.9%). risk of COVID-19 case, 18.9% higher, RR 1.19, _p_ = 0.58, treatment 8 of 148 (5.4%), control 20 of 416 (4.8%), OR converted to RR. Gönenli et al., 12/16/2020, retrospective, Turkey, Middle East, preprint, survey, 4 authors.Share Tweet
Submit Corrections or Comments12/14 Late
Sofian et al., Wiener Medizinische Wochenschrift, doi:10.1007/s10354-020-00793-8 (Peer Reviewed) SARS-CoV‑2, a virus with many faces: a series of cases with prolonged persistence of COVID-19 symptoms Details Report on a series of 10 patients experiencing prolonged COVID-19 symptoms that were given HCQ 250mg bid for 5 days, with resolution of symptoms in all cases, and patients reporting they felt much better 2 days after treatment initiation. 12/14 Details SourceLate treatment study Late treatment study Sofian et al., Wiener Medizinische Wochenschrift, doi:10.1007/s10354-020-00793-8 (Peer Reviewed) SARS-CoV‑2, a virus with many faces: a series of cases with prolonged persistence of COVID-19 symptoms Report on a series of 10 patients experiencing prolonged COVID-19 symptoms that were given HCQ 250mg bid for 5 days, with resolution of symptoms in all cases, and patients reporting they felt much better 2 days after treatment initiation. Sofian et al., 12/14/2020, peer-reviewed, 7 authors.
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Submit Corrections or Comments12/14 Late
Orioli et al., Diabetes & Metabolic Syndrome: Clinical Research & Reviews, doi:10.1016/j.dsx.2020.12.020 (Peer Reviewed) death, ↓12.7%, p=1.00 Clinical characteristics and short-term prognosis of in-patients with diabetes and COVID-19: A retrospective study from an academiccenter in Belgium
Details Small retrospective study of 73 diabetic patients in Belgium, 55 HCQ patients, showing HCQ RR 0.87, _p_ = 1.0. 12/14 Details SourceLate treatment study Late treatment study Orioli et al., Diabetes & Metabolic Syndrome: Clinical Research & Reviews, doi:10.1016/j.dsx.2020.12.020 (Peer Reviewed) Clinical characteristics and short-term prognosis of in-patients with diabetes and COVID-19: A retrospective study from an academic
center in Belgium
Small retrospective study of 73 diabetic patients in Belgium, 55 HCQ patients, showing HCQ RR 0.87, _p_ = 1.0. risk of death, 12.7% lower, RR 0.87, _p_ = 1.00, treatment 8 of 55 (14.5%), control 3 of 18 (16.7%). Orioli et al., 12/14/2020, retrospective, Belgium, Europe, peer-reviewed, 9 authors.Share Tweet
Submit Corrections or Comments12/14 Late
Naseem et al., medRxiv, doi:10.1101/2020.12.13.20247254 (Preprint) death, ↓33.3%, p=0.34 Predicting mortality in SARS-COV-2 (COVID-19) positive patients in the inpatient setting using a Novel Deep Neural Network Details Retrospective 1,214 hospitalized patients in Pakistan, 77 HCQ patients, showing 33% lower mortality with HCQ, multivariate Cox HR 0.67, _p_ = 0.34. 12/14 Details SourceLate treatment study Late treatment study Naseem et al., medRxiv, doi:10.1101/2020.12.13.20247254 (Preprint) Predicting mortality in SARS-COV-2 (COVID-19) positive patients in the inpatient setting using a Novel Deep Neural Network Retrospective 1,214 hospitalized patients in Pakistan, 77 HCQ patients, showing 33% lower mortality with HCQ, multivariate Cox HR
0.67, _p_ = 0.34.
risk of death, 33.3% lower, RR 0.67, _p_ = 0.34, treatment 77, control 1137, multivariate Cox. Naseem et al., 12/14/2020, retrospective, Pakistan, South Asia, preprint, 5 authors.Share Tweet
Submit Corrections or Comments12/14 Late
Tan et al., Virus Research, doi:10.1016/j.virusres.2020.198262(Peer Reviewed)
hosp. time, ↓35.2%, p=0.04 A retrospective comparison of drugs against COVID-19 Details Retrospective 333 patients in China, with only 8 HCQ patients, showing shorter duration of hospitalization withHCQ.
12/14 Details SourceLate treatment study Late treatment study Tan et al., Virus Research, doi:10.1016/j.virusres.2020.198262
(Peer Reviewed)
A retrospective comparison of drugs against COVID-19 Retrospective 333 patients in China, with only 8 HCQ patients, showing shorter duration of hospitalization with HCQ. hospitalization time, 35.2% lower, relative time 0.65, _p_ = 0.04, treatment 8, control 277. Tan et al., 12/14/2020, retrospective, China, Asia, peer-reviewed, 7authors.
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Submit Corrections or Comments12/11 Late
Bielza et al., Journal of the American Medical Directors Association, doi:10.1016/j.jamda.2020.12.003 (Peer Reviewed) death, ↓21.5%, p=0.09 Clinical characteristics, frailty and mortality of residents with COVID-19 in nursing homes of a region of Madrid Details Retrospective 630 elderly patients in Spain showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.78, _p_ = 0.09. HCQ was used more often with patients that were hospitalized (24% versus 3% use in the nursing homes). Med.. 12/11 Details SourceLate treatment study Late treatment study Bielza et al., Journal of the American Medical Directors Association, doi:10.1016/j.jamda.2020.12.003 (Peer Reviewed) Clinical characteristics, frailty and mortality of residents with COVID-19 in nursing homes of a region of Madrid Retrospective 630 elderly patients in Spain showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.78, _p_ = 0.09. HCQ was used more often with patients that were hospitalized (24% versus 3% use in the nursing homes). Median age 87. risk of death, 21.5% lower, RR 0.78, _p_ = 0.09, treatment 33 of 91 (36.3%), control 249 of 539 (46.2%). Bielza et al., 12/11/2020, retrospective, Spain, Europe, peer-reviewed, median age 87.0, 24 authors.
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Submit Corrections or Comments12/11 Early
Sogut et al., The American Journal of Emergency Medicine, doi:10.1016/j.ajem.2020.12.014 (Peer Reviewed) (not included in thestudy count)
safety analysis
Safety and efficacy of hydroxychloroquine in 152 outpatients with confirmed COVID-19: A pilot observational study Details Safety study of 152 outpatients concluding that HCQ is safe for COVID-19, was well tolerated, and was not associated with a risk of ventricular arrhythmia due to drug-induced QTc interval prolongation. 12/11 Details SourceEarly treatment study Early treatment study Sogut et al., The American Journal of Emergency Medicine, doi:10.1016/j.ajem.2020.12.014 (Peer Reviewed) (not included in the
study count)
Safety and efficacy of hydroxychloroquine in 152 outpatients with confirmed COVID-19: A pilot observational study Safety study of 152 outpatients concluding that HCQ is safe for COVID-19, was well tolerated, and was not associated with a risk of ventricular arrhythmia due to drug-induced QTc interval prolongation. Sogut et al., 12/11/2020, peer-reviewed, 10 authors.Share Tweet
Submit Corrections or Comments12/11 PrEP
Jung et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.12.003 (Peer Reviewed) death, ↓59.3%, p=1.00 Effect of hydroxychloroquine pre-exposure on infection with SARS-CoV-2 in rheumatic disease patients: A population-based cohortstudy
Details Retrospective cohort study of RA and SLE patients not showing a significant difference in PCR+ cases. PCR+ does not distinguish asymptomatic cases or severity. There was only one death which was in the control group. No other information .. 12/11 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Jung et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.12.003 (Peer Reviewed) Effect of hydroxychloroquine pre-exposure on infection with SARS-CoV-2 in rheumatic disease patients: A population-based cohort
study
Retrospective cohort study of RA and SLE patients not showing a significant difference in PCR+ cases. PCR+ does not distinguish asymptomatic cases or severity. There was only one death which was in the control group. No other information on severity is provided. 33% of the control group used HCQ within the last year. Remaining confounding by differences in the nature and severity of rheumaticdisease is likely.
risk of death, 59.3% lower, RR 0.41, _p_ = 1.00, treatment 0 of 649 (0.0%), control 1 of 1417 (0.1%), continuity correction due to zeroevent.
risk of COVID-19 case, 13.1% higher, RR 1.13, _p_ = 0.86, treatment 15 of 649 (2.3%), control 31 of 1417 (2.2%), adjusted. Jung et al., 12/11/2020, retrospective, South Korea, Asia, peer-reviewed, 6 authors.Share Tweet
Submit Corrections or Comments12/10 Late
Alqassieh et al., F1000Research, Preprint (Preprint) hosp. time, ↓18.2%, p=0.11 Clinical characteristics and predictors of the duration of hospital stay in COVID-19 patients in Jordan Details Prospective observational study of 131 COVID-19 patients in Jordan, showing 18% shorter hospital stay with HCQ, _p_ = 0.11. 12/10 Details SourceLate treatment study Late treatment study Alqassieh et al., F1000Research, Preprint (Preprint) Clinical characteristics and predictors of the duration of hospital stay in COVID-19 patients in Jordan Prospective observational study of 131 COVID-19 patients in Jordan, showing 18% shorter hospital stay with HCQ, _p_ = 0.11. hospitalization time, 18.2% lower, relative time 0.82, _p_ = 0.11, treatment 63, control 68. Alqassieh et al., 12/10/2020, prospective, Jordan, Middle East, preprint, 10 authors.
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Italian Council of State (News) (not included in the study count)news
Consiglio di Stato, sì all'uso dell'idrossiclorachina per la curadel Covid
Details Consiglio di Stato ruling in Italy re-establishes the right of Italian MDs to prescribe HCQ, which was suspended after the retracted Lancet study. 12/10 Details SourceNews
News
Italian Council of State (News) (not included in the study count) Consiglio di Stato, sì all'uso dell'idrossiclorachina per la curadel Covid
Consiglio di Stato ruling in Italy re-establishes the right of Italian MDs to prescribe HCQ, which was suspended after the retractedLancet study.
Italian Council of State et al., 12/10/2020, preprint.Share Tweet
Submit Corrections or Comments12/9 Late
Johnston et al., EClinicalMedicine, doi:10.1016/j.eclinm.2021.100773 (preprint 12/9) (Peer Reviewed) hosp., ↓29.9%, p=0.73 Hydroxychloroquine with or Without Azithromycin for Treatment of Early SARS-CoV-2 Infection Among High-Risk Outpatient Adults: A Randomized Clinical Trial Details Small early terminated late treatment RCT comparing vitamin C + folic acid, HCQ + folic acid, and HCQ+AZ, showing non-statistically significantly lower hospitalization with HCQ/HCQ+AZ, and faster viral clearance with HCQ. Enrollment was a.. 12/9 Details SourceLate treatment study Late treatment study Johnston et al., EClinicalMedicine, doi:10.1016/j.eclinm.2021.100773 (preprint 12/9) (Peer Reviewed) Hydroxychloroquine with or Without Azithromycin for Treatment of Early SARS-CoV-2 Infection Among High-Risk Outpatient Adults: A Randomized Clinical Trial Small early terminated late treatment RCT comparing vitamin C + folic acid, HCQ + folic acid, and HCQ+AZ, showing non-statistically significantly lower hospitalization with HCQ/HCQ+AZ, and faster viral clearance with HCQ. Enrollment was a median of 5.9 days after onset (6.2 and 6.3 in the treatment arms). The median time to viral clearance for vitamin C + folic acid was 8 days in the preprint but changed to 7 days in the published paper without explanation. Low risk patients, median age 37, no deaths (not matching the title which claims "high risk"). Post hoc addition of a new Ct threshold to obscure the statistically significant faster clearance. No analysis for time from symptom onset. Authors identify (relatively) low and high risk cohorts, but do not provide either viral shedding or symptom resolution results for the cohorts. NCT04354428. For other issues see
.
twitter.com/Covid19Crusher/status/1358066110105542658 risk of hospitalization, 29.9% lower, RR 0.70, _p_ = 0.73, treatment 5 of 148 (3.4%), control 4 of 83 (4.8%), HCQ + folic acid and HCQ + AZ vs. vitamin C + folic acid. risk of no recovery, 2.0% lower, RR 0.98, _p_ = 0.95, treatment 30 of 60 (50.0%), control 34 of 72 (47.2%), adjusted, HCQ + folic acid vs. vitamin C + folic acid. risk of no recovery, 9.9% higher, RR 1.10, _p_ = 0.70, treatment 34 of 65 (52.3%), control 34 of 72 (47.2%), adjusted, HCQ + AZ vs. vitamin C + folic acid. time to viral-, 28.6% lower, relative time 0.71, treatment 49, control 52, median time, HCQ + folic acid vs. vitamin C + folic acid. time to viral-, 14.3% lower, relative time 0.86, treatment 51, control 52, median time, HCQ + AZ vs. vitamin C + folic acid. risk of no virological cure, 38.3% lower, RR 0.62, _p_ = 0.05, treatment 6 of 49 (12.2%), control 12 of 52 (23.1%), adjusted, HCQ + folic acid vs. vitamin C + folic acid. risk of no virological cure, 20.0% lower, RR 0.80, _p_ = 0.49, treatment 11 of 51 (21.6%), control 12 of 52 (23.1%), adjusted, HCQ + AZ vs. vitamin C + folic acid. Johnston et al., 12/9/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 30 authors, dosage 400mg bid day 1, 200mg biddays 2-10.
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Submit Corrections or Comments12/9 Early
Agusti et al., Enfermedades Infecciosas y Microbiología Clínica, doi:10.1016/j.eimc.2020.10.023 (Peer Reviewed) progression, ↓68.4%, p=0.21 Efficacy and safety of hydroxychloroquine in healthcare professionals with mild SARS-CoV-2 infection: prospective, non-randomized trial Details Small trial of low dose HCQ for healthcare workers with mild SARS-CoV-2 showing 68% lower progression to pneumonia, _p_ = 0.21, and faster, but not statistically significant viral clearance. There were no ICU admissions or deaths.Prospect..
12/9 Details SourceEarly treatment study Early treatment study Agusti et al., Enfermedades Infecciosas y Microbiología Clínica, doi:10.1016/j.eimc.2020.10.023 (Peer Reviewed) Efficacy and safety of hydroxychloroquine in healthcare professionals with mild SARS-CoV-2 infection: prospective, non-randomized trial Small trial of low dose HCQ for healthcare workers with mild SARS-CoV-2 showing 68% lower progression to pneumonia, _p_ = 0.21, and faster, but not statistically significant viral clearance. There were no ICU admissions or deaths. Prospective non-randomized study. The figures and supplementary data are not currently available in the pre-proof edition. risk of disease progression, 68.4% lower, RR 0.32, _p_ = 0.21, treatment 2 of 87 (2.3%), control 4 of 55 (7.3%), pneumonia. time to viral-, 31.8% lower, relative time 0.68, treatment 87,
control 55.
Agusti et al., 12/9/2020, prospective, Spain, Europe, peer-reviewed, median age 37.0, 13 authors, dosage 400mg bid day 1, 200mg bid days2-5.
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Guglielmetti et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2020.11.012 (Peer Reviewed) death, ↓35.0%, p=0.22 Severe COVID-19 pneumonia in Piacenza, Italy – a cohort study of the first pandemic wave Details Retrospective 218 hospitalized patients in Italy showing non-statistically significant 35% lower mortality with HCQ, hazard ratio aHR 0.65 . 12/9 Details SourceLate treatment study Late treatment study Guglielmetti et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2020.11.012 (Peer Reviewed) Severe COVID-19 pneumonia in Piacenza, Italy – a cohort study of the first pandemic wave Retrospective 218 hospitalized patients in Italy showing non-statistically significant 35% lower mortality with HCQ, hazard
ratio aHR 0.65 .
risk of death, 35.0% lower, RR 0.65, _p_ = 0.22, treatment 181, control 37, adjusted, multivariable Cox. Guglielmetti et al., 12/9/2020, retrospective, Italy, Europe, peer-reviewed, 16 authors.Share Tweet
Submit Corrections or Comments12/7 PEP
Barnabas et al., Annals of Internal Medicine, doi:10.7326/M20-6519(Peer Reviewed)
hosp., ↑3.7%, p=1.00 Hydroxychloroquine for Post-exposure Prophylaxis to Prevent Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: ARandomized Trial
Details Early terminated PEP RCT comparing HCQ and vitamin C with 781 low-risk patients (83% household contacts), reporting no significant differences. Different results were reported at IDWeek from the AIM results. The study enrolled people wi.. 12/7 Details SourcePost Exposure Prophylaxis study Post Exposure Prophylaxis study Barnabas et al., Annals of Internal Medicine, doi:10.7326/M20-6519
(Peer Reviewed)
Hydroxychloroquine for Post-exposure Prophylaxis to Prevent Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: ARandomized Trial
Early terminated PEP RCT comparing HCQ and vitamin C with 781 low-risk patients (83% household contacts), reporting no significantdifferences.
Different results were reported at IDWeek from the AIM results. The study enrolled people with their last exposure within 4 days, i.e., if someone was exposed for 30 days in a row, they could be enrolled anywhere from day 1 to day 34. Therefore many were likely infected earlier than the enrollment date. Note that PCR has a very high false negative rates, e.g., 100% on day 1 and 67% on day 4 here.
50% of infections were detected by day 4. With the PCR false negatives and treatment delays it is likely that a majority of infections happened before enrollment or before HCQ can reach therapeutic levels. Significantly more cases were caught at baseline in the control group (54 vs. 29 for HCQ) and excluded from analysis. The early presentation stated that therapy started one day after enrollment and study supplies were sent to the participant "either by courier or mail". The published paper changes this to "courier delivery within 48 hours". Overall delays are unclear but may be: time since first exposure - unlimited time from last exposure to enrollment - 10% reported as >= 5 days time to telehealth meeting - 1 day (3 days if Friday enrollment?) time to receive medication - <48 hours (including weekends?) Symptomatic in this study was based on CDC-defined symptoms which contain symptoms that may be due to HCQ side effects. Some results have not been reported, including symptomatic @28 days. The study uses a low dosage over an extended period, therapeutic levels may only be reached nearer to day 14, if at all, so day 28 results should be more informative when available (although labeled a PEP trial, with the low dosage and continuous exposure for most participants it is more of a PrEP/PEP trial where benefit might be seen later as HCQ levels increase).Endpoints were:
Primary outcomes:
PCR+ @28 days mITT - aHR 1.16 PCR+ @14 days mITT - aHR 1.10 IDWeek report was different:aHR 0.99
PCR+ @14 days ITT - aHR 0.81Secondary outcomes:
PCR+ symptomatic @28 days - NOT REPORTED YET duration of shedding - NOT REPORTED YET Not in study protocol: PCR+ cumulative symptomatic @14 days - aHR 1.23 . Dose in first 24 hours - 0.8g (compare with Boulware et al. 2g) Dose in first 5 days - 1.6g (compare with Boulware et al. 3.8g) Other research suggests vitamin C may be beneficial for COVID-19, e.g. . No information on severity of cases is provided. Binary PCR does not distinguish replication-competence. There were 2 COVID-19 hospitalizations, one in each group. Side effects were similar for HCQ and placebo. 83% medication adherence at day 14.NCT04328961
ncbi.nlm.nih.gov/pmc/articles/PMC7240870/ researchsquare.com/article/rs-52778/v2 clinicaltrials.gov/ct2/show/NCT04328961 risk of hospitalization, 3.7% higher, RR 1.04, _p_ = 1.00, treatment 1 of 407 (0.2%), control 1 of 422 (0.2%). risk of COVID-19 case, 27.0% higher, RR 1.27, _p_ = 0.33, treatment 43 of 353 (12.2%), control 33 of 336 (9.8%), adjusted, day 14 symptomatic mITT PCR+ AIM. risk of COVID-19 case, 23.0% higher, RR 1.23, _p_ = 0.41, treatment 40 of 317 (12.6%), control 32 of 309 (10.4%), adjusted, day 14 symptomatic mITT PCR+ IDWeek. risk of COVID-19 case, 10.0% higher, RR 1.10, _p_ = 0.66, treatment 53 of 353 (15.0%), control 45 of 336 (13.4%), adjusted, day 14 PCR+mITT AIM.
risk of COVID-19 case, 1.0% lower, RR 0.99, _p_ = 0.97, treatment 46 of 317 (14.5%), control 43 of 309 (13.9%), adjusted, day 14 PCR+ mITTIDWeek.
risk of COVID-19 case, 19.0% lower, RR 0.81, _p_ = 0.23, treatment 82 of 387 (21.2%), control 99 of 393 (25.2%), adjusted, day 14 PCR+ ITTAIM.
Barnabas et al., 12/7/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 30 authors.Share Tweet
Submit Corrections or Comments12/4 Late
Ozturk et al., Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfaa271 (Peer Reviewed) death, ↓43.9%, p=0.14 Mortality analysis of COVID-19 infection in chronic kidney disease, haemodialysis and renal transplant patients compared with patients without kidney disease: a nationwide analysis from Turkey Details Retrospective 1210 hospitalized patients in Turkey focused on chronic kidney disease, haemodialysis and renal transplant patients, but also showing lower mortality with HCQ. Subject to confounding by indication. 12/4 Details SourceLate treatment study Late treatment study Ozturk et al., Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfaa271 (Peer Reviewed) Mortality analysis of COVID-19 infection in chronic kidney disease, haemodialysis and renal transplant patients compared with patients without kidney disease: a nationwide analysis from Turkey Retrospective 1210 hospitalized patients in Turkey focused on chronic kidney disease, haemodialysis and renal transplant patients, but also showing lower mortality with HCQ. Subject to confounding by
indication.
risk of death, 43.9% lower, RR 0.56, _p_ = 0.14, treatment 165 of 1127 (14.6%), control 6 of 23 (26.1%), CQ/HCQ. Ozturk et al., 12/4/2020, retrospective, Turkey, Middle East, peer-reviewed, 70 authors.Share Tweet
Submit Corrections or Comments12/4 Late
Modrák et al., medRxiv, doi:10.1101/2020.12.03.20239863(Preprint)
death, ↓59.0%, p=0.04 Detailed disease progression of 213 patients hospitalized with Covid-19 in the Czech Republic: An exploratory analysis Details Retrospective 213 hospitalized patients in Czech Republic showing lower mortality with HCQ. Subject to confounding by indication. 12/4 Details SourceLate treatment study Late treatment study Modrák et al., medRxiv, doi:10.1101/2020.12.03.20239863 (Preprint) Detailed disease progression of 213 patients hospitalized with Covid-19 in the Czech Republic: An exploratory analysis Retrospective 213 hospitalized patients in Czech Republic showing lower mortality with HCQ. Subject to confounding by indication. risk of death, 59.0% lower, RR 0.41, _p_ = 0.04, treatment 108, control 105, Cox (single). Modrák et al., 12/4/2020, retrospective, Czech Republic, Europe, preprint, 26 authors.
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Submit Corrections or Comments12/4 Late
Peng et al., Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfaa288 (Peer Reviewed) progression, ↓10.8%, p=0.63 Early versus late acute kidney injury among patients with COVID-19—a multicenter study from Wuhan, China Details Retrospective 4020 hospitalized patients in China showing non-statistically significant lower risk of acute kidney injury with HCQ. 12/4 Details SourceLate treatment study Late treatment study Peng et al., Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfaa288 (Peer Reviewed) Early versus late acute kidney injury among patients with COVID-19—a multicenter study from Wuhan, China Retrospective 4020 hospitalized patients in China showing non-statistically significant lower risk of acute kidney injury with
HCQ.
risk of disease progression, 10.8% lower, RR 0.89, _p_ = 0.63, treatment 29 of 453 (6.4%), control 256 of 3567 (7.2%), CQ/HCQ risk ofAKI.
Peng et al., 12/4/2020, retrospective, China, Asia, peer-reviewed, 21authors.
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Submit Corrections or Comments12/2 PEP
Wiseman et al., medRxiv, doi:10.1101/2020.11.29.20235218 (Preprint) (meta analysis - not included in study count) cases, ↓42.0%, p=0.04 Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data Details 6th independent analysis showing efficacy from the Boulware PEP trial. This prospective analysis corrects an error in the NEJM paper where shipping delays are omitted (still not corrected). 42% reduction in COVID-19 (9.6% vs. 16.5%),RR..
12/2 Details SourcePost Exposure Prophylaxis study Post Exposure Prophylaxis study Wiseman et al., medRxiv, doi:10.1101/2020.11.29.20235218 (Preprint) (meta analysis - not included in study count) Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data 6th independent analysis showing efficacy from the Boulware PEP
trial.
This prospective analysis corrects an error in the NEJM paper where shipping delays are omitted (still not corrected). 42% reduction in COVID-19 (9.6% vs. 16.5%), RR 0.58 , _p_=0.044, for the original trial 3 day specification. risk of COVID-19 case, 42.0% lower, RR 0.58, _p_ = 0.04, <= 3 daysafter exposure.
Wiseman et al., 12/2/2020, preprint, 4 authors.Share Tweet
Submit Corrections or Comments12/1 Late
Capsoni et al., Research Square, doi:10.21203/rs.3.rs-113418/v1(Preprint)
ventilation, ↓40.0%, p=0.30 CPAP Treatment In COVID-19 Patients: A Retrospective Observational Study In The Emergency Department Details Small 52 patient retrospective study of patients with acute respiratory failure showing lower rates of intubation with HCQ. 12/1 Details SourceLate treatment study Late treatment study Capsoni et al., Research Square, doi:10.21203/rs.3.rs-113418/v1
(Preprint)
CPAP Treatment In COVID-19 Patients: A Retrospective Observational Study In The Emergency Department Small 52 patient retrospective study of patients with acute respiratory failure showing lower rates of intubation with HCQ. risk of mechanical ventilation, 40.0% lower, RR 0.60, _p_ = 0.30, treatment 12 of 40 (30.0%), control 6 of 12 (50.0%). Capsoni et al., 12/1/2020, retrospective, Italy, Europe, preprint, 13authors.
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Submit Corrections or Comments11/30 Late
Abdulrahman et al., medRxiv, doi:10.1101/2020.11.25.20234914(Preprint)
death, ↓16.7%, p=1.00 The efficacy and safety of hydroxychloroquine in COVID19 patients : a multicenter national retrospective cohort Details Retrospective medical record analysis of acute care patients in Bahrain not showing a significant effect of HCQ. Confounding by indication is likely. Matching appears not to have matched for baseline severity - 17.5% of HCQ patientsrequ..
11/30 Details SourceLate treatment study Late treatment study Abdulrahman et al., medRxiv, doi:10.1101/2020.11.25.20234914
(Preprint)
The efficacy and safety of hydroxychloroquine in COVID19 patients : a multicenter national retrospective cohort Retrospective medical record analysis of acute care patients in Bahrain not showing a significant effect of HCQ. Confounding by indication is likely. Matching appears not to have matched for baseline severity - 17.5% of HCQ patients required oxygen while only 12.6% of control patients did. risk of death, 16.7% lower, RR 0.83, _p_ = 1.00, treatment 5 of 223 (2.2%), control 6 of 223 (2.7%), PSM. risk of combined intubation/death, 75.0% higher, RR 1.75, _p_ = 0.24, treatment 12 of 223 (5.4%), control 7 of 223 (3.1%), adjusted, PSM. Abdulrahman et al., 11/30/2020, retrospective, Bahrain, Middle East, preprint, 9 authors.Share Tweet
Submit Corrections or Comments11/29 Late
Abd-Elsalam et al., Biological Trace Element Research, doi:10.1007/s12011-020-02512-1 (Peer Reviewed) Do Zinc Supplements Enhance the Clinical Efficacy of Hydroxychloroquine?: a Randomized, Multicenter Trial Details 191 patient RCT in Egypt comparing the addition of zinc to HCQ, not showing a significant difference. Clinical recovery at 28 days was 79.2% in the zinc group and 77.9% control, _p_ = 0.969. Mechanical ventilation was used with 4patients..
11/29 Details SourceLate treatment study Late treatment study Abd-Elsalam et al., Biological Trace Element Research, doi:10.1007/s12011-020-02512-1 (Peer Reviewed) Do Zinc Supplements Enhance the Clinical Efficacy of Hydroxychloroquine?: a Randomized, Multicenter Trial 191 patient RCT in Egypt comparing the addition of zinc to HCQ, not showing a significant difference. Clinical recovery at 28 days was 79.2% in the zinc group and 77.9% control, _p_ = 0.969. Mechanical ventilation was used with 4 patients in the zinc group and 6 control. There were 5 deaths in each group. No information on baseline zinc values was recorded. We note that Egypt has a low rate of zinc deficiency so supplementation is less likely to be helpful in Egypt ncbi.nlm.nih.gov/pmc/articles/PMC3510072/ ncbi.nlm.nih.gov/pmc/articles/PMC3510072/bin/pone.0050568.s003.xls Abd-Elsalam et al., 11/29/2020, peer-reviewed, 10 authors.
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Submit Corrections or Comments11/28 Late
Lambermont et al., Critical Care Explorations, doi:10.1097/CCE.0000000000000305 (Peer Reviewed) death, ↓32.3%, p=0.46 Predictors of Mortality and Effect of Drug Therapies in Mechanically Ventilated Patients With Coronavirus Disease 2019: A Multicenter Cohort Study Details Retrospective 247 mechanically ventilated patients showing lower mortality with HCQ, but not statistically significant on multiple Cox regression. The paper gives the p value for multiple Cox (0.46) and simple Cox (0.02), but doesnot sp..
11/28 Details SourceLate treatment study Late treatment study Lambermont et al., Critical Care Explorations, doi:10.1097/CCE.0000000000000305 (Peer Reviewed) Predictors of Mortality and Effect of Drug Therapies in Mechanically Ventilated Patients With Coronavirus Disease 2019: A Multicenter Cohort Study Retrospective 247 mechanically ventilated patients showing lower mortality with HCQ, but not statistically significant on multiple Cox
regression.
The paper gives the p value for multiple Cox (0.46) and simple Cox (0.02), but does not specify the adjusted risk values. risk of death, 32.3% lower, RR 0.68, _p_ = 0.46, treatment 97 of 225 (43.1%), control 14 of 22 (63.6%), adjusted. Lambermont et al., 11/28/2020, retrospective, Belgium, Europe, peer-reviewed, 15 authors.Share Tweet
Submit Corrections or Comments11/28 N/A
Ruiz et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106247 (Peer Reviewed)dosing study
Hydroxychloroquine lung pharmacokinetics in critically ill patients infected with COVID-19 Details HCQ lung pharmacokinetic study confirming that lung concentrations can be much higher than plasma. The median lung epithelial lining fluid concentration was 38 times higher than plasma concentrations. 22 COVID-19 patients, median age 59... 11/28 Details SourceN/A
N/A
Ruiz et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106247 (Peer Reviewed) Hydroxychloroquine lung pharmacokinetics in critically ill patients infected with COVID-19 HCQ lung pharmacokinetic study confirming that lung concentrations can be much higher than plasma. The median lung epithelial lining fluid concentration was 38 times higher than plasma concentrations. 22 COVID-19 patients, median age59.5.
Dosage determinations in studies assuming equilibrium between epithelium and plasma concentrations may lead to overly high dosages. Authors find the median ELF concentration of HCQ above the maximum EC50 value for 400 mg x 1 /day and 200 mg x 3 /day, 7-12 days after treatment initiation. Ruiz et al., 11/28/2020, peer-reviewed, 14 authors.Share Tweet
Submit Corrections or Comments11/28 Late
Rodriguez-Gonzalez et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106249 (Peer Reviewed) death, ↓22.8%, p=0.26 COVID-19 in hospitalized patients in Spain: a cohort study inMadrid
Details Retrospective 1255 patients in Spain showing lower mortality with HCQ. Subject to confounding byindication.
11/28 Details SourceLate treatment study Late treatment study Rodriguez-Gonzalez et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106249 (Peer Reviewed) COVID-19 in hospitalized patients in Spain: a cohort study in
Madrid
Retrospective 1255 patients in Spain showing lower mortality with HCQ. Subject to confounding by indication. risk of death, 22.8% lower, RR 0.77, _p_ = 0.26, treatment 251 of 1148 (21.9%), control 17 of 60 (28.3%). Rodriguez-Gonzalez et al., 11/28/2020, retrospective, Spain, Europe, peer-reviewed, 20 authors.Share Tweet
Submit Corrections or Comments11/27 Late
van Halem et al., BMC Infect Dis., doi:10.1186/s12879-020-05605-3(Peer Reviewed)
death, ↓31.6%, p=0.05 Risk factors for mortality in hospitalized patients with COVID-19 at the start of the pandemic in Belgium: a retrospective cohort study Details Retrospective 319 hospitalized patients in Belgium showing lower mortality with HCQ, although not reported to be statistically significant. 11/27 Details SourceLate treatment study Late treatment study van Halem et al., BMC Infect Dis., doi:10.1186/s12879-020-05605-3
(Peer Reviewed)
Risk factors for mortality in hospitalized patients with COVID-19 at the start of the pandemic in Belgium: a retrospective cohort study Retrospective 319 hospitalized patients in Belgium showing lower mortality with HCQ, although not reported to be statisticallysignificant.
risk of death, 31.6% lower, RR 0.68, _p_ = 0.05, treatment 34 of 164 (20.7%), control 47 of 155 (30.3%). van Halem et al., 11/27/2020, retrospective, Belgium, Europe, peer-reviewed, 10 authors.Share Tweet
Submit Corrections or Comments11/24 Late
Abbas et al., Int. J. Clin. Pract., doi:10.1111/ijcp.13856 (PeerReviewed)
Assessment of COVID-19 Treatment containing both Hydroxychloroquine and Azithromycin: A Natural Clinical Trial Details Prospective study of 161 hospitalized patients in Iraq showing HCQ+AZ appears to help recovery. Most mortality was in patients that were already in critical condition on admission and died before treatment could be effective. 11/24 Details SourceLate treatment study Late treatment study Abbas et al., Int. J. Clin. Pract., doi:10.1111/ijcp.13856 (Peer
Reviewed)
Assessment of COVID-19 Treatment containing both Hydroxychloroquine and Azithromycin: A Natural Clinical Trial Prospective study of 161 hospitalized patients in Iraq showing HCQ+AZ appears to help recovery. Most mortality was in patients that were already in critical condition on admission and died before treatmentcould be effective.
Abbas et al., 11/24/2020, prospective, Iraq, Middle East, peer-reviewed, 8 authors.Share Tweet
Submit Corrections or Comments11/23 Late
Qin et al., Thrombosis Research, doi:10.1016/j.thromres.2020.11.020 (Peer Reviewed) death, ↓34.3%, p=0.61 Low molecular weight heparin and 28-day mortality among patients with coronavirus disease 2019: A cohort study in the early epidemicera
Details Low molecular weight heparin study also showing results for HCQ treatment, unadjusted HCQ mortality relative risk RR 0.66, _p_ = 0.61. 11/23 Details SourceLate treatment study Late treatment study Qin et al., Thrombosis Research, doi:10.1016/j.thromres.2020.11.020
(Peer Reviewed)
Low molecular weight heparin and 28-day mortality among patients with coronavirus disease 2019: A cohort study in the early epidemicera
Low molecular weight heparin study also showing results for HCQ treatment, unadjusted HCQ mortality relative risk RR 0.66, _p_ = 0.61. risk of death, 34.3% lower, RR 0.66, _p_ = 0.61, treatment 3 of 43 (7.0%), control 75 of 706 (10.6%). Qin et al., 11/23/2020, retrospective, China, Asia, peer-reviewed, 17authors.
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Submit Corrections or Comments11/21 PrEP
Revollo et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkaa477 (Peer Reviewed) cases, ↓23.0%, p=0.52 Hydroxychloroquine pre-exposure prophylaxis for COVID-19 inhealthcare workers
Details Retrospective PrEP analysis with 69 healthcare workers on PrEP HCQ, and 418 control. Authors report PCR and IgG results, with no baseline results for either. Authors note they "identified 69 HCWs receiving HCQ" while providing .. 11/21 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Revollo et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkaa477 (Peer Reviewed) Hydroxychloroquine pre-exposure prophylaxis for COVID-19 in
healthcare workers
Retrospective PrEP analysis with 69 healthcare workers on PrEP HCQ,and 418 control.
Authors report PCR and IgG results, with no baseline results for either. Authors note they "identified 69 HCWs receiving HCQ" while providing no information as to why or when they started HCQ. No conclusions can be drawn from this study because many workers may have been positive before starting HCQ. Only 14% of workers chose to use HCQ and they may have been motivated to do so because they had aninfection.
Authors perform several different adjustments, finding very different results. No information on death, hospitalization, symptoms, or severity is provided. Details on timing of serology and baseline serology status is not provided. Potential bias due to self-selectionfor risk.
25% of infections were detected before 7 days, indicating that they actually happened earlier (PCR false positive is very high initially). It is likely that many infections were before HCQ could reachtherapeutic levels.
risk of COVID-19 case, 23.0% lower, RR 0.77, _p_ = 0.52, treatment 16 of 69 (23.2%), control 65 of 418 (15.6%), adjusted, PSM risk of PCR+. risk of COVID-19 case, 43.0% higher, RR 1.43, _p_ = 0.42, treatment 17 of 60 (28.3%), control 62 of 404 (15.3%), adjusted, PSM risk ofIgG+.
Revollo et al., 11/21/2020, retrospective, Spain, Europe, peer-reviewed, 16 authors.Share Tweet
Submit Corrections or Comments11/20 Early
Omrani et al., EClinicalMedicine, doi:10.1016/j.eclinm.2020.100645(Peer Reviewed)
hosp., ↓12.5%, p=1.00 Randomized double-blinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure ofnon-severe Covid-19
Details Low risk patient RCT for HCQ+AZ and HCQ vs. control, not showing any significant differences. Authors note that the results are not applicable to higher risk patients; that positive PCR may simply reflect detection of inactive (non-infec.. 11/20 Details SourceEarly treatment study Early treatment study Omrani et al., EClinicalMedicine, doi:10.1016/j.eclinm.2020.100645
(Peer Reviewed)
Randomized double-blinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure ofnon-severe Covid-19
Low risk patient RCT for HCQ+AZ and HCQ vs. control, not showing any significant differences. Authors note that the results are not applicable to higher risk patients; that positive PCR may simply reflect detection of inactive (non-infectious) viral remnants; that an alternative dosage regimen may be more effective; and that medication adherence was unknown. HCQ dosing was 600mg/day for 1 week, therapeutic levels may not be reached for several days. There were no deaths or serious adverseevents.
risk of hospitalization, 12.5% lower, RR 0.88, _p_ = 1.00, treatment 7 of 304 (2.3%), control 4 of 152 (2.6%), HCQ+AZ or HCQ vs. control. risk of symptomatic at day 21, 25.8% lower, RR 0.74, _p_ = 0.58, treatment 9 of 293 (3.1%), control 6 of 145 (4.1%), HCQ+AZ or HCQ vs.control.
risk of Ct<=40 at day 14, 10.3% higher, RR 1.10, _p_ = 0.13, treatment 223 of 295 (75.6%), control 98 of 143 (68.5%), HCQ+AZ or HCQvs. control.
Omrani et al., 11/20/2020, Randomized Controlled Trial, Qatar, Middle East, peer-reviewed, 19 authors, dosage 600mg days 1-6.Share Tweet
Submit Corrections or Comments11/19 Late
Falcone et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa563 (Peer Reviewed) death, ↓65.0%, p=0.20 Role of low-molecular weight heparin in hospitalized patients with SARS-CoV-2 pneumonia: a prospective observational study Details Prospective observational study of 315 hospitalized patients in Italy showing 65% lower mortality with HCQ. The median treatment delay was 6 days for survivors and 6.5 days for non-survivors. Mortality relative risk: RR 0.35, _p_ = 0.2, pr.. 11/19 Details SourceLate treatment study Late treatment study Falcone et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa563 (Peer Reviewed) Role of low-molecular weight heparin in hospitalized patients with SARS-CoV-2 pneumonia: a prospective observational study Prospective observational study of 315 hospitalized patients in Italy showing 65% lower mortality with HCQ. The median treatment delay was 6 days for survivors and 6.5 days for non-survivors. Mortality relative
risk:
RR 0.35, _p_ = 0.2, propensity score matched RR 0.75, _p_ = 0.36, multivariate Cox regression RR 0.43, _p_ < 0.001, univariate Cox regression risk of death, 65.0% lower, RR 0.35, _p_ = 0.20, treatment 40 of 238 (16.8%), control 30 of 77 (39.0%), adjusted, PSM. risk of death, 25.0% lower, RR 0.75, _p_ = 0.36, treatment 40 of 238 (16.8%), control 30 of 77 (39.0%), adjusted, multivariate Coxregression.
risk of death, 57.0% lower, RR 0.43, _p_ < 0.001, treatment 40 of 238 (16.8%), control 30 of 77 (39.0%), adjusted, univariate Coxregression.
Falcone et al., 11/19/2020, prospective, Italy, Europe, peer-reviewed, 19 authors.Share Tweet
Submit Corrections or Comments11/18 Late
Budhiraja et al., medRxiv, doi:10.1101/2020.11.16.20232223(Preprint)
death, ↓65.4%, p<0.0001 Clinical Profile of First 1000 COVID-19 Cases Admitted at Tertiary Care Hospitals and the Correlates of their Mortality: An IndianExperience
Details Retrospective 976 hospitalized patients with 834 treated with HCQ+AZ showing HCQ mortality relative risk RR 0.35, _p_ < 0.0001. Note that in this case HCQ was recommended for mild/moderate cases, so more severe cases may not have receivedH..
11/18 Details SourceLate treatment study Late treatment study Budhiraja et al., medRxiv, doi:10.1101/2020.11.16.20232223
(Preprint)
Clinical Profile of First 1000 COVID-19 Cases Admitted at Tertiary Care Hospitals and the Correlates of their Mortality: An IndianExperience
Retrospective 976 hospitalized patients with 834 treated with HCQ+AZ showing HCQ mortality relative risk RR 0.35, _p_ < 0.0001. Note that in this case HCQ was recommended for mild/moderate cases, so more severe cases may not have received HCQ (which may also be why they became severe cases). We note that this is opposite to a common bias in HCQ studies - in many cases HCQ was more likely to be given to moresevere cases.
risk of death, 65.4% lower, RR 0.35, _p_ < 0.001, treatment 69 of 834 (8.3%), control 34 of 142 (23.9%). Budhiraja et al., 11/18/2020, retrospective, India, South Asia, preprint, 12 authors.Share Tweet
Submit Corrections or Comments11/17 Late
Boari et al, Biosci. Rep., doi:10.1042/BSR20203455 (Peer Reviewed) death, ↓54.5%, p<0.001 Prognostic factors and predictors of outcome in patients with COVID-19 and related pneumonia: a retrospective cohort study Details Retrospective 258 hospitalized patients in Italy showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.455, _p_<0.001. Data is in the supplementaryappendix.
11/17 Details SourceLate treatment study Late treatment study Boari et al, Biosci. Rep., doi:10.1042/BSR20203455 (Peer Reviewed) Prognostic factors and predictors of outcome in patients with COVID-19 and related pneumonia: a retrospective cohort study Retrospective 258 hospitalized patients in Italy showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.455, _p_<0.001. Data is in the supplementary appendix. risk of death, 54.5% lower, RR 0.45, _p_ < 0.001, treatment 41 of 202 (20.3%), control 25 of 56 (44.6%). Boari et al., 11/17/2020, retrospective, Italy, Europe, peer-reviewed, 20 authors.
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Submit Corrections or Comments11/13 Late
Sheshah et al., Diabetes Research and Clinical Practice, doi:10.1016/j.diabres.2020.108538 (Peer Reviewed) death, ↓80.0%, p<0.001 Prevalence of Diabetes, Management and Outcomes among Covid-19 Adult Patients Admitted in a Specialized Tertiary Hospital in Riyadh,Saudi Arabia
Details Retrospective 300 hospitalized patients in Saudi Arabia showing HCQ adjusted odds ratio aOR 0.12, _p_ < 0.001. 11/13 Details SourceLate treatment study Late treatment study Sheshah et al., Diabetes Research and Clinical Practice, doi:10.1016/j.diabres.2020.108538 (Peer Reviewed) Prevalence of Diabetes, Management and Outcomes among Covid-19 Adult Patients Admitted in a Specialized Tertiary Hospital in Riyadh,
Saudi Arabia
Retrospective 300 hospitalized patients in Saudi Arabia showing HCQ adjusted odds ratio aOR 0.12, _p_ < 0.001. risk of death, 80.0% lower, RR 0.20, _p_ < 0.001, treatment 267, control 33, OR converted to RR. Sheshah et al., 11/13/2020, retrospective, Saudi Arabia, Middle East, peer-reviewed, 8 authors.Share Tweet
Submit Corrections or Comments11/12 Early
Simova et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100813 (Peer Reviewed) hosp., ↓93.8%, p=0.01 Hydroxychloroquine for prophylaxis and treatment of COVID-19 inhealth care workers
Details 100% reduction in hospitalization and cases with early treatment using HCQ+AZ+zinc. Brief report on healthcare workers in Bulgaria. 0 hospitalizations with treatment vs. 2 for control 0 PCR+ at day 14 with treatment vs. 3 for control 33.. 11/12 Details SourceEarly treatment study Early treatment study Simova et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100813 (Peer Reviewed) Hydroxychloroquine for prophylaxis and treatment of COVID-19 in
health care workers
100% reduction in hospitalization and cases with early treatment using HCQ+AZ+zinc. Brief report on healthcare workers in Bulgaria. 0 hospitalizations with treatment vs. 2 for control 0 PCR+ at day 14 with treatment vs. 3 for control 33 treatment patients and 5 control patients. No serious adverse events. This paper reports on both PEP and early treatment, we have separated the two studies. risk of hospitalization, 93.8% lower, RR 0.06, _p_ = 0.01, treatment 0 of 33 (0.0%), control 2 of 5 (40.0%), continuity correction due tozero event.
risk of viral+ at day 14, 95.8% lower, RR 0.04, _p_ = 0.001, treatment 0 of 33 (0.0%), control 3 of 5 (60.0%), continuity correction due to zero event. Simova et al., 11/12/2020, retrospective, Bulgaria, Europe, peer-reviewed, 5 authors, dosage 200mg tid days 1-14.Share Tweet
Submit Corrections or Comments11/12 PEP
Simova et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100813 (Peer Reviewed) cases, ↓92.7%, p=0.01 Hydroxychloroquine for prophylaxis and treatment of COVID-19 inhealth care workers
Details 100% reduction in cases with HCQ+zinc post-exposure prophylaxis. Brief report for healthcare workers in Bulgaria. 0 cases with treatment vs. 3 for control. 156 treatment patients and 48 control patients. No serious adverse events. This.. 11/12 Details SourcePost Exposure Prophylaxis study Post Exposure Prophylaxis study Simova et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100813 (Peer Reviewed) Hydroxychloroquine for prophylaxis and treatment of COVID-19 in
health care workers
100% reduction in cases with HCQ+zinc post-exposure prophylaxis. Brief report for healthcare workers in Bulgaria. 0 cases with treatment vs. 3 for control. 156 treatment patients and 48 control patients. No serious adverse events. This paper reports on both PEP and early treatment, we have separated the two studies. risk of COVID-19 case, 92.7% lower, RR 0.07, _p_ = 0.01, treatment 0 of 156 (0.0%), control 3 of 48 (6.2%), continuity correction due tozero event.
Simova et al., 11/12/2020, retrospective, Bulgaria, Europe, peer-reviewed, 5 authors.Share Tweet
Submit Corrections or Comments11/12 N/A
Tchounga et al., Journal of Pharmaceutical and Biomedical Analysis, doi:10.1016/j.jpba.2020.113761 (Peer Reviewed) (meta analysis - not included in study count)meta-analysis
Composition analysis of falsified chloroquine phosphate samples seized during the COVID-19 pandemic Details Analysis of fake CQ tablets finding: - no CQ in six samples, substituted with metronidazole (at sub-therapeutic levels) or paracetamol. - trace levels of paracetamol and chloramphenicol in four and two samples respectively. - CQ levelst..
11/12 Details SourceN/A
N/A
Tchounga et al., Journal of Pharmaceutical and Biomedical Analysis, doi:10.1016/j.jpba.2020.113761 (Peer Reviewed) (meta analysis - not included in study count) Composition analysis of falsified chloroquine phosphate samples seized during the COVID-19 pandemic Analysis of fake CQ tablets finding: - no CQ in six samples, substituted with metronidazole (at sub-therapeutic levels) or paracetamol. - trace levels of paracetamol and chloramphenicol in four and two samples respectively. - CQ levels too low in two samples. Tchounga et al., 11/12/2020, peer-reviewed, 7 authors.Share Tweet
Submit Corrections or Comments11/11 Late
Águila-Gordo et al., Revista Española de Geriatría y Gerontología, doi:10.1016/j.regg.2020.09.006 (Peer Reviewed) death, ↓67.0%, p=0.10 Mortality and associated prognostic factors in elderly and very elderly hospitalized patients with respiratory disease COVID-19 Details 67% lower mortality with HCQ. Retrospective 416 elderly patients in Spain showing adjusted HCQ mortality hazard ratio HR 0.33, _p_ = 0.1. 11/11 Details SourceLate treatment study Late treatment study Águila-Gordo et al., Revista Española de Geriatría y Gerontología, doi:10.1016/j.regg.2020.09.006 (Peer Reviewed) Mortality and associated prognostic factors in elderly and very elderly hospitalized patients with respiratory disease COVID-19 67% lower mortality with HCQ. Retrospective 416 elderly patients in Spain showing adjusted HCQ mortality hazard ratio HR 0.33, _p_ = 0.1. risk of death, 67.0% lower, RR 0.33, _p_ = 0.10, treatment 151 of 346 (43.6%), control 47 of 70 (67.1%), adjusted. Águila-Gordo et al., 11/11/2020, retrospective, Spain, Europe, peer-reviewed, mean age 84.4, 6 authors.
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Submit Corrections or Comments11/9 Late
Khamis et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.11.008 (Peer Reviewed) Randomized Controlled Open Label Trial on the Use of Favipiravir Combined with Inhaled Interferon beta-1b in Hospitalized Patients with Moderate to Severe COVID-19 Pneumonia Details Small 89 patient RCT comparing favipiravir and inhaled interferon with HCQ for moderate to severe COVID-19 pneumonia, not finding significant differences. 11/9 Details SourceLate treatment study Late treatment study Khamis et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.11.008 (Peer Reviewed) Randomized Controlled Open Label Trial on the Use of Favipiravir Combined with Inhaled Interferon beta-1b in Hospitalized Patients with Moderate to Severe COVID-19 Pneumonia Small 89 patient RCT comparing favipiravir and inhaled interferon with HCQ for moderate to severe COVID-19 pneumonia, not finding significant differences. Khamis et al., 11/9/2020, peer-reviewed, 11 authors.
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Submit Corrections or Comments11/9 Late
Rodriguez et al., Medicina Intensiva, doi:10.1016/j.medine.2020.05.005 (Peer Reviewed) death, ↓59.0%, p=0.23 Severe infection due to the SARS-CoV-2 coronavirus: Experience of a tertiary hospital with COVID-19 patients during the 2020 pandemic Details Small prospective study of 43 hospitalized patients with 39 taking HCQ, showing unadjusted mortality relative risk RR 0.41, _p_=0.23. 11/9 Details SourceLate treatment study Late treatment study Rodriguez et al., Medicina Intensiva, doi:10.1016/j.medine.2020.05.005 (Peer Reviewed) Severe infection due to the SARS-CoV-2 coronavirus: Experience of a tertiary hospital with COVID-19 patients during the 2020 pandemic Small prospective study of 43 hospitalized patients with 39 taking HCQ, showing unadjusted mortality relative risk RR 0.41, _p_=0.23. risk of death, 59.0% lower, RR 0.41, _p_ = 0.23, treatment 8 of 39 (20.5%), control 2 of 4 (50.0%). Rodriguez et al., 11/9/2020, prospective, Spain, Europe, peer-reviewed, 13 authors.
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Submit Corrections or Comments11/9 Late
Self et al., JAMA, doi:10.1001/jama.2020.22240 (Peer Reviewed) death, ↑6.2%, p=0.84 Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial Details Early terminated very late stage (65% on supplemental oxygen) RCT with 242 HCQ and 237 control patients not showing a significant difference, 28 day mortality adjusted odds ratio aOR 0.93 . For the subgroup not on supplemental.. 11/9 Details SourceLate treatment study Late treatment study Self et al., JAMA, doi:10.1001/jama.2020.22240 (Peer Reviewed) Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial Early terminated very late stage (65% on supplemental oxygen) RCT with 242 HCQ and 237 control patients not showing a significant difference, 28 day mortality adjusted odds ratio aOR 0.93 . For the subgroup not on supplemental oxygen at baseline (relatively early treatment), the odds ratio for the 7 point outcome scale is:
aOR 0.61
Dosage may be too low: Dose in first 24 hours - 1g (compare to Boulware et al. 2g) Dose in 5 days - 2.4g (compare to Boulware et al. 3.8g) Dosage note: Boulware 2g within 24 hours includes the second day dose. Note two important differences with the RECOVERY/SOLIDARITY dosage which is believed to be dangerously high - in RECOVERY/SOLIDARITY the total dose is much higher, which is problematic because the half-life of HCQ is very long, and it is given to patients that are already in very serious condition. Note the paper reports primary outcome values with OR>1 favoring HCQ, we have converted to OR<1 favoring HCQ. Subgroup analysis is in the supplemental appendix. risk of death, 6.2% higher, RR 1.06, _p_ = 0.84, treatment 25 of 241 (10.4%), control 25 of 236 (10.6%), adjusted, OR converted to RR. Self et al., 11/9/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 33 authors.Share Tweet
Submit Corrections or Comments11/9 Late
Brown et al., Annals of the American Thoracic Society, doi:10.1513/AnnalsATS.202008-940OC (Peer Reviewed) Hydroxychloroquine vs. Azithromycin for Hospitalized Patients with COVID-19 (HAHPS): Results of a Randomized, Active Comparator Trial Details Small early terminated very late stage (86% on oxygen, 44% enrolled in the ICU) RCT comparing HCQ vs. AZ, not finding a significant difference between the two treatments. There is no comparison with a control group. HCQ patients not in th.. 11/9 Details SourceLate treatment study Late treatment study Brown et al., Annals of the American Thoracic Society, doi:10.1513/AnnalsATS.202008-940OC (Peer Reviewed) Hydroxychloroquine vs. Azithromycin for Hospitalized Patients with COVID-19 (HAHPS): Results of a Randomized, Active Comparator Trial Small early terminated very late stage (86% on oxygen, 44% enrolled in the ICU) RCT comparing HCQ vs. AZ, not finding a significant difference between the two treatments. There is no comparison with a control group. HCQ patients not in the ICU at enrollment (slightly earlier treatment) did better, OR 0.95 vs. 1.13. HCQ dosage is relatively low: Dose in first 24 hours - 1g (compare to Boulware et al. 2g) Dose in 5 days - 2.4g (compare to Boulware et al. 3.8g) Brown et al., 11/9/2020, peer-reviewed, 17 authors.
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Submit Corrections or Comments11/9 Late
Núñez-Gil et al., Intern. Emerg. Med., doi:10.1007/s11739-020-02543-5 (Peer Reviewed) death, ↓7.9%, p=0.005 Mortality risk assessment in Spain and Italy, insights of the HOPECOVID-19 registry
Details Retrospective database study of 1,021 patients in Ecuador, Germany, Italy, and Spain, showing HCQ propensity score adjusted mortality odds ratio aOR 0.88, _p_=0.005. 11/9 Details SourceLate treatment study Late treatment study Núñez-Gil et al., Intern. Emerg. Med., doi:10.1007/s11739-020-02543-5 (Peer Reviewed) Mortality risk assessment in Spain and Italy, insights of the HOPE
COVID-19 registry
Retrospective database study of 1,021 patients in Ecuador, Germany, Italy, and Spain, showing HCQ propensity score adjusted mortality odds ratio aOR 0.88, _p_=0.005. risk of death, 7.9% lower, RR 0.92, _p_ = 0.005, treatment 200 of 686 (29.2%), control 100 of 268 (37.3%), adjusted, OR converted to RR. Núñez-Gil et al., 11/9/2020, retrospective, database analysis, multiple countries, Europe, peer-reviewed, median age 68.0, 49authors.
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Submit Corrections or Comments11/6 PrEP
Mathai et al., J. Marine Medical Society, doi:10.4103/jmms.jmms_115_20 (Peer Reviewed) cases, ↓89.5%, p<0.0001 Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 in health-care workers: A single-center experience Details 90% reduction in cases with HCQ pre-exposure prophylaxis. Retrospective 604 healthcare workers. 11/6 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Mathai et al., J. Marine Medical Society, doi:10.4103/jmms.jmms_115_20 (Peer Reviewed) Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 in health-care workers: A single-center experience 90% reduction in cases with HCQ pre-exposure prophylaxis. Retrospective 604 healthcare workers. risk of COVID-19 case, 89.5% lower, RR 0.10, _p_ < 0.001, treatment 10 of 491 (2.0%), control 22 of 113 (19.5%). risk of COVID-19 case, 88.5% lower, RR 0.12, _p_ < 0.001, treatment 5 of 491 (1.0%), control 10 of 113 (8.8%), symptomatic. Mathai et al., 11/6/2020, retrospective, India, South Asia, peer-reviewed, 3 authors.
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Submit Corrections or Comments11/6 PrEP
Datta et al., Journal of Vaccines & Vaccination, S6:1000002 (PeerReviewed)
No Role of HCQ in COVID-19 Prophylaxis: A Survey amongst IndianDoctors
Details Survey of Indian doctors not finding a significant effect of HCQ prophylaxis, _p_ = 0.54. We do not know the actual results for this study - the numbers for prophylaxis in Table 1 appear to be incorrect. They do not match the total using H.. 11/6 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Datta et al., Journal of Vaccines & Vaccination, S6:1000002 (Peer
Reviewed)
No Role of HCQ in COVID-19 Prophylaxis: A Survey amongst IndianDoctors
Survey of Indian doctors not finding a significant effect of HCQ prophylaxis, _p_ = 0.54. We do not know the actual results for this study - the numbers for prophylaxis in Table 1 appear to be incorrect. They do not match the total using HCQ, and they are identical to the numbers for the analysis by specialty. Datta et al., 11/6/2020, peer-reviewed, 7 authors.Share Tweet
Submit Corrections or Comments11/6 PEP
Dhibar et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106224 (Peer Reviewed) cases, ↓41.0%, p=0.03 Post Exposure Prophylaxis with Hydroxychloroquine (HCQ) for the Prevention of COVID-19, a Myth or a Reality? The PEP-CQ Study Details 41% reduction in cases with HCQ PEP. Prospective open label trial with 132 HCQ patients and 185 control patients showing RR 0.59, _p_=0.03. 50% reduction in PCR+ cases, 44% reduction in symptomatic cases. No serious adverse events. Relati.. 11/6 Details SourcePost Exposure Prophylaxis study Post Exposure Prophylaxis study Dhibar et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106224 (Peer Reviewed) Post Exposure Prophylaxis with Hydroxychloroquine (HCQ) for the Prevention of COVID-19, a Myth or a Reality? The PEP-CQ Study 41% reduction in cases with HCQ PEP. Prospective open label trial with 132 HCQ patients and 185 control patients showing RR 0.59,
_p_=0.03.
50% reduction in PCR+ cases, 44% reduction in symptomatic cases. No serious adverse events. Relatively low dosage, the PEP group received HCQ 800mg on day one followed by 400mg once weekly for 3weeks. NCT04408456
risk of COVID-19 case, 41.0% lower, RR 0.59, _p_ = 0.03, treatment 14 of 132 (10.6%), control 36 of 185 (19.5%), adjusted. risk of COVID-19 case, 50.0% lower, RR 0.50, _p_ = 0.04, treatment 10 of 132 (7.6%), control 28 of 185 (15.1%), adjusted, PCR+. risk of symptomatic case, 43.9% lower, RR 0.56, _p_ = 0.21, treatment 6 of 132 (4.5%), control 15 of 185 (8.1%), adjusted. Dhibar et al., 11/6/2020, prospective, India, South Asia, peer-reviewed, 13 authors.Share Tweet
Submit Corrections or Comments11/5 Late
Maldonado et al., Nefrología, doi:10.1016/j.nefro.2020.09.002(Peer Reviewed)
death, ↓90.9%, p=0.17 COVID-19 incidence and outcomes in a home dialysis unit in Madrid (Spain) at the height of the pandemic Details Very small retrospective of 12 dialysis patients showing 1/11 deaths with HCQ and 1/1 without HCQ. 11/5 Details SourceLate treatment study Late treatment study Maldonado et al., Nefrología, doi:10.1016/j.nefro.2020.09.002
(Peer Reviewed)
COVID-19 incidence and outcomes in a home dialysis unit in Madrid (Spain) at the height of the pandemic Very small retrospective of 12 dialysis patients showing 1/11 deaths with HCQ and 1/1 without HCQ. risk of death, 90.9% lower, RR 0.09, _p_ = 0.17, treatment 1 of 11 (9.1%), control 1 of 1 (100.0%). Maldonado et al., 11/5/2020, retrospective, Spain, Europe, peer-reviewed, 10 authors.Share Tweet
Submit Corrections or Comments11/5 Late
Rodriguez-Nava et al., Mayo Clinic Proceedings: Innovations, Quality & Outcomes (Peer Reviewed) death, ↑6.3%, p=0.77 Clinical characteristics and risk factors for mortality of hospitalized patients with COVID-19 in a community hospital: A retrospective cohort study Details Retrospective 313 patients, mostly critical stage and mostly requiring respiratory support, showing unadjusted RR 1.06, _p_ = 0.77. Confounding by indicationlikely.
11/5 Details SourceLate treatment study Late treatment study Rodriguez-Nava et al., Mayo Clinic Proceedings: Innovations, Quality & Outcomes (Peer Reviewed) Clinical characteristics and risk factors for mortality of hospitalized patients with COVID-19 in a community hospital: A retrospective cohort study Retrospective 313 patients, mostly critical stage and mostly requiring respiratory support, showing unadjusted RR 1.06, _p_ = 0.77. Confounding by indication likely. risk of death, 6.3% higher, RR 1.06, _p_ = 0.77, treatment 22 of 65 (33.8%), control 79 of 248 (31.9%), unadjusted. Rodriguez-Nava et al., 11/5/2020, retrospective, USA, North America, peer-reviewed, median age 68.0, 8 authors.
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Submit Corrections or Comments11/4 Late
Salazar et al., The American Journal of Pathology, doi:10.1016/j.ajpath.2020.10.008 (Peer Reviewed) death, ↑37.0%, p=0.28 Significantly Decreased Mortality in a Large Cohort of Coronavirus Disease 2019 (COVID-19) Patients Transfused Early with Convalescent Plasma Containing High-Titer Anti–Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein IgG Details Convalescent plasma study also showing mortality based on HCQ treatment, unadjusted hazard ratio uHR 1.37, _p_ = 0.28. Confounding by indication is likely. 11/4 Details SourceLate treatment study Late treatment study Salazar et al., The American Journal of Pathology, doi:10.1016/j.ajpath.2020.10.008 (Peer Reviewed) Significantly Decreased Mortality in a Large Cohort of Coronavirus Disease 2019 (COVID-19) Patients Transfused Early with Convalescent Plasma Containing High-Titer Anti–Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein IgG Convalescent plasma study also showing mortality based on HCQ treatment, unadjusted hazard ratio uHR 1.37, _p_ = 0.28. Confounding by indication is likely. risk of death, 37.0% higher, RR 1.37, _p_ = 0.28, treatment 12 of 92 (13.0%), control 80 of 811 (9.9%). Salazar et al., 11/4/2020, retrospective, USA, North America, peer-reviewed, 19 authors.
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Submit Corrections or Comments11/4 Early
Cadegiani et al., medRxiv, doi:10.1101/2020.10.31.20223883(Preprint)
death, ↓81.2%, p=0.21 Early COVID-19 Therapy with Azithromycin Plus Nitazoxanide, Ivermectin or Hydroxychloroquine in Outpatient Settings Significantly Reduced Symptoms Compared to Known Outcomes in Untreated Patients Details Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population,ev..
11/4 Details SourceEarly treatment study Early treatment study Cadegiani et al., medRxiv, doi:10.1101/2020.10.31.20223883
(Preprint)
Early COVID-19 Therapy with Azithromycin Plus Nitazoxanide, Ivermectin or Hydroxychloroquine in Outpatient Settings Significantly Reduced Symptoms Compared to Known Outcomes in Untreated Patients Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, even for those outcomes not influenced by placebo effect, at least when combined with azithromycin, and vitamin C, D and zinc in the majority of the cases. 585 patients with mean treatment delay 2.9 days. There was no hospitalization, mechanical ventilation, or mortality with treatment. The size of the treatment groups in this trial can be found in . researchsquare.com/article/rs-98106/v1 risk of death, 81.2% lower, RR 0.19, _p_ = 0.21, treatment 0 of 159 (0.0%), control 2 of 137 (1.5%), continuity correction due to zero event, control group 1. risk of mechanical ventilation, 95.1% lower, RR 0.05, _p_ < 0.001, treatment 0 of 159 (0.0%), control 9 of 137 (6.6%), continuity correction due to zero event, control group 1. risk of hospitalization, 98.3% lower, RR 0.02, _p_ < 0.001, treatment 0 of 159 (0.0%), control 27 of 137 (19.7%), continuity correction due to zero event, control group 1. Cadegiani et al., 11/4/2020, prospective, Brazil, South America, preprint, 4 authors, dosage 400mg days 1-5.Share Tweet
Submit Corrections or Comments11/3 PrEP
Behera et al., PLoS ONE, doi:10.1371/journal.pone.0247163 (preprint 11/3) (Peer Reviewed) cases, ↓27.9%, p=0.29 Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study Details Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQOR 0.56, ..
11/3 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Behera et al., PLoS ONE, doi:10.1371/journal.pone.0247163 (preprint 11/3) (Peer Reviewed) Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQ OR 0.56, _p_ = 0.29 Ivermectin OR 0.27, _p_ < 0.001 Vitamin C OR 0.82, _p_ = 0.58 risk of COVID-19 case, 27.9% lower, RR 0.72, _p_ = 0.29, treatment 7 of 19 (36.8%), control 179 of 353 (50.7%), adjusted, OR converted to RR, model 2 conditional logistic regression. risk of COVID-19 case, 26.3% lower, RR 0.74, _p_ = 0.25, treatment 7 of 19 (36.8%), control 179 of 353 (50.7%), OR converted to RR, matched
pair analysis.
Behera et al., 11/3/2020, retrospective, India, South Asia, peer-reviewed, 13 authors.Share Tweet
Submit Corrections or Comments11/2 Late
López et al., Annals of Pediatrics, doi:10.1016/j.anpedi.2020.10.017 (Peer Reviewed) progression, ↓64.3%, p=0.02 Telemedicine follow-ups for COVID-19: experience in a tertiaryhospital
Details Retrospective 72 pediatric patients showing HCQ associated with a shorter duration of fever (_p_=0.023), less progression (_p_=0.016), and fewer return visits to the ER(_p_=0.017).
11/2 Details SourceLate treatment study Late treatment study López et al., Annals of Pediatrics, doi:10.1016/j.anpedi.2020.10.017 (Peer Reviewed) Telemedicine follow-ups for COVID-19: experience in a tertiary
hospital
Retrospective 72 pediatric patients showing HCQ associated with a shorter duration of fever (_p_=0.023), less progression (_p_=0.016), and fewer return visits to the ER (_p_=0.017). risk of disease progression, 64.3% lower, RR 0.36, _p_ = 0.02, treatment 5 of 36 (13.9%), control 14 of 36 (38.9%). López et al., 11/2/2020, retrospective, Spain, Europe, peer-reviewed, 7 authors.Share Tweet
Submit Corrections or Comments10/31 Early
Szente Fonseca et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101906 (Peer Reviewed) hosp., ↓64.0%, p=0.0008 Risk of Hospitalization for Covid-19 Outpatients Treated with Various Drug Regimens in Brazil: Comparative Analysis Details 64% lower hospitalization with HCQ. Retrospective 717 patients in Brazil with early treatment, adjusted OR 0.32, _p_=0.00081, for HCQ versus no medication, and OR 0.45, _p_=0.0065, for HCQ vs. anything else. 10/31 Details SourceEarly treatment study Early treatment study Szente Fonseca et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101906 (Peer Reviewed) Risk of Hospitalization for Covid-19 Outpatients Treated with Various Drug Regimens in Brazil: Comparative Analysis 64% lower hospitalization with HCQ. Retrospective 717 patients in Brazil with early treatment, adjusted OR 0.32, _p_=0.00081, for HCQ versus no medication, and OR 0.45, _p_=0.0065, for HCQ vs. anything
else.
risk of hospitalization, 64.0% lower, RR 0.36, _p_ < 0.001, treatment 25 of 175 (14.3%), control 89 of 542 (16.4%), adjusted, OR converted to RR, HCQ vs. nothing. risk of hospitalization, 50.5% lower, RR 0.49, _p_ = 0.006, treatment 25 of 175 (14.3%), control 89 of 542 (16.4%), adjusted, OR converted to RR, HCQ vs. anything else. Szente Fonseca et al., 10/31/2020, retrospective, Brazil, South America, peer-reviewed, mean age 50.6, 10 authors, dosage 400mg bid day 1, 400mg qd days 2-5.Share Tweet
Submit Corrections or Comments10/30 Late
Tehrani et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.071 (Peer Reviewed) death, ↓13.4%, p=0.63 Risk factors for mortality in adult COVID-19 patients; frailty predicts fatal outcome in older patients Details Retrospective 255 hospitalized patients, 65 treated with HCQ, showing unadjusted RR 0.87, _p_=0.63. Confounding by indication is likely. 10/30 Details SourceLate treatment study Late treatment study Tehrani et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.071 (Peer Reviewed) Risk factors for mortality in adult COVID-19 patients; frailty predicts fatal outcome in older patients Retrospective 255 hospitalized patients, 65 treated with HCQ, showing unadjusted RR 0.87, _p_=0.63. Confounding by indication is likely. risk of death, 13.4% lower, RR 0.87, _p_ = 0.63, treatment 16 of 65 (24.6%), control 54 of 190 (28.4%). Tehrani et al., 10/30/2020, retrospective, Sweden, Europe, peer-reviewed, 5 authors.
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Submit Corrections or Comments10/27 PrEP
Arleo et al., medRxiv, doi:10.1101/2020.10.26.20219154 (Preprint) death, ↓50.0%, p=0.67 Clinical Course and Outcomes of coronavirus disease 2019 (COVID-19) in Rheumatic Disease Patients on Immunosuppression: A case Cohort Study at a Single Center with a Significantly Diverse Population Details Retrospective hospitalized rheumatic disease patients showing 50% lower mortality for patients on HCQ. 10/27 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Arleo et al., medRxiv, doi:10.1101/2020.10.26.20219154 (Preprint) Clinical Course and Outcomes of coronavirus disease 2019 (COVID-19) in Rheumatic Disease Patients on Immunosuppression: A case Cohort Study at a Single Center with a Significantly Diverse Population Retrospective hospitalized rheumatic disease patients showing 50% lower mortality for patients on HCQ. risk of death, 50.0% lower, RR 0.50, _p_ = 0.67, treatment 1 of 20 (5.0%), control 5 of 50 (10.0%), all patients. risk of death, 52.0% lower, RR 0.48, _p_ = 0.64, treatment 1 of 10 (10.0%), control 5 of 24 (20.8%), inpatients. Arleo et al., 10/27/2020, retrospective, USA, North America, preprint, 5 authors.
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Choi et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.062 (Peer Reviewed) viral- time, ↑22.0%, p<0.0001 Comparison of antiviral effect for mild-to-moderate COVID-19 cases between lopinavir/ritonavir versus hydroxychloroquine: A nationwide propensity score-matched cohort study Details Health insurance database analysis failing to adjust for disease severity and not finding a significant difference in time to PCR- for LPV/r and HCQ. There are large differences in severity across groups. Authors did PSM but chose notto..
10/27 Details SourceLate treatment study Late treatment study Choi et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.062 (Peer Reviewed) Comparison of antiviral effect for mild-to-moderate COVID-19 cases between lopinavir/ritonavir versus hydroxychloroquine: A nationwide propensity score-matched cohort study Health insurance database analysis failing to adjust for disease severity and not finding a significant difference in time to PCR- for
LPV/r and HCQ.
There are large differences in severity across groups. Authors did PSM but chose not to prioritize severity, resulting in incomparable groups, e.g., baseline pneumonia of 44% in the HCQ group and 15% in the control group (after PSM). Authors note this but offer no explanation for not correcting for severity: "However, the disease severity and proportion of accompanying pneumonia were still significantly higher in the LPV/rand HCQ-group".
median time to PCR-, 22.0% higher, relative time 1.22, _p_ < 0.001, treatment 701, control 701. Choi et al., 10/27/2020, retrospective, database analysis, South Korea, Asia, peer-reviewed, 8 authors.Share Tweet
Submit Corrections or Comments10/26 Late
Frontera et al., Research Square, doi:10.21203/rs.3.rs-94509/v1(Preprint)
death, ↓37.0%, p=0.01 Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study Details Retrospective 3,473 hospitalized patients showing lower mortality with HCQ+zinc. 10/26 Details SourceLate treatment study Late treatment study Frontera et al., Research Square, doi:10.21203/rs.3.rs-94509/v1
(Preprint)
Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study Retrospective 3,473 hospitalized patients showing lower mortalitywith HCQ+zinc.
risk of death, 37.0% lower, RR 0.63, _p_ = 0.01, treatment 121 of 1006 (12.0%), control 424 of 2467 (17.2%), adjusted, PSM. risk of death, 24.0% lower, RR 0.76, _p_ = 0.02, treatment 121 of 1006 (12.0%), control 424 of 2467 (17.2%), adjusted, regression. Frontera et al., 10/26/2020, retrospective, USA, North America, preprint, median age 64.0, 14 authors.Share Tweet
Submit Corrections or Comments10/26 Early
Derwand et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106214 (preprint 7/3) (Peer Reviewed) death, ↓79.4%, p=0.12 COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin: A RetrospectiveCase Series Study
Details 79% lower mortality and 82% lower hospitalization with early HCQ+AZ+Z. No cardiac side effects. Retrospective 518 patients (141 treated, 377 control). 10/26 Details SourceEarly treatment study Early treatment study Derwand et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106214 (preprint 7/3) (Peer Reviewed) COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin: A Retrospective
Case Series Study
79% lower mortality and 82% lower hospitalization with early HCQ+AZ+Z. No cardiac side effects. Retrospective 518 patients (141 treated, 377 control). risk of death, 79.4% lower, RR 0.21, _p_ = 0.12, treatment 1 of 141 (0.7%), control 13 of 377 (3.4%), OR converted to RR. risk of hospitalization, 81.6% lower, RR 0.18, _p_ < 0.001, treatment 4 of 141 (2.8%), control 58 of 377 (15.4%), OR converted to RR. Derwand et al., 10/26/2020, retrospective, USA, North America, peer-reviewed, 3 authors, dosage 200mg bid days 1-5.Share Tweet
Submit Corrections or Comments10/24 PrEP
Goenka et al., SSRN, doi:10.2139/ssrn.3689618 (Preprint) IgG+, ↓87.2%, p=0.03 Seroprevalence of COVID-19 Amongst Health Care Workers in a Tertiary Care Hospital of a Metropolitan City from India Details Study of SARS-CoV-2-IgG antibodies in 1122 health care workers in India finding 87% lower positives for adequate HCQ prophylaxis, 1.3% HCQ versus 12.3% for no HCQ prophylaxis. Adequate prophylaxis is defined as 400mg 1/wk for >6weeks.
10/24 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Goenka et al., SSRN, doi:10.2139/ssrn.3689618 (Preprint) Seroprevalence of COVID-19 Amongst Health Care Workers in a Tertiary Care Hospital of a Metropolitan City from India Study of SARS-CoV-2-IgG antibodies in 1122 health care workers in India finding 87% lower positives for adequate HCQ prophylaxis, 1.3% HCQ versus 12.3% for no HCQ prophylaxis. Adequate prophylaxis is defined as 400mg 1/wk for >6 weeks. risk of IgG positive, 87.2% lower, RR 0.13, _p_ = 0.03, treatment 1 of 77 (1.3%), control 115 of 885 (13.0%), adjusted, OR converted to
RR.
Goenka et al., 10/24/2020, retrospective, India, South Asia, preprint, 11 authors.Share Tweet
Submit Corrections or Comments10/23 Late
Coll et al., American Journal of Transplantation, doi:10.1111/ajt.16369 (Peer Reviewed) death, ↓45.6%, p<0.0001 Covid‐19 in transplant recipients: the spanish experience Details Retrospective 652 transplant recipient patients in Spain showing 46% lower mortality for patients treated with HCQ, unadjusted relative risk RR 0.54, _p_<0.0001. 10/23 Details SourceLate treatment study Late treatment study Coll et al., American Journal of Transplantation, doi:10.1111/ajt.16369 (Peer Reviewed) Covid‐19 in transplant recipients: the spanish experience Retrospective 652 transplant recipient patients in Spain showing 46% lower mortality for patients treated with HCQ, unadjusted relative risk RR 0.54, _p_<0.0001. risk of death, 45.6% lower, RR 0.54, _p_ < 0.001, treatment 55 of 307 (17.9%), control 108 of 328 (32.9%). Coll et al., 10/23/2020, retrospective, Spain, Europe, peer-reviewed, median age 61.0, 29 authors.
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Submit Corrections or Comments10/21 Late
Lano et al., Clinical Kidney Journal, 13:5, October 2020, 878–888, doi:10.1093/ckj/sfaa199 (Peer Reviewed) death, ↓33.1%, p=0.28 Risk factors for severity of COVID-19 in chronic dialysis patients from a multicentre French cohort Details 33% lower mortality with HCQ+AZ, _p_=0.28. Retrospective 122 French dialysis patients. 69% lower combined mortality/ICU, _p_=0.11, for the subgroup not requiring O2 on diagnosis (slightly earlier treatment). 10/21 Details SourceLate treatment study Late treatment study Lano et al., Clinical Kidney Journal, 13:5, October 2020, 878–888, doi:10.1093/ckj/sfaa199 (Peer Reviewed) Risk factors for severity of COVID-19 in chronic dialysis patients from a multicentre French cohort 33% lower mortality with HCQ+AZ, _p_=0.28. Retrospective 122 French
dialysis patients.
69% lower combined mortality/ICU, _p_=0.11, for the subgroup not requiring O2 on diagnosis (slightly earlier treatment). risk of death, 33.1% lower, RR 0.67, _p_ = 0.28, treatment 56, control 66, adjusted, OR converted to RR. risk of combined death/ICU, 38.9% lower, RR 0.61, _p_ = 0.23, treatment 17 of 56 (30.4%), control 28 of 66 (42.4%), adjusted, ORconverted to RR.
risk of combined death/ICU, 68.7% lower, RR 0.31, _p_ = 0.11, treatment 4 of 36 (11.1%), control 11 of 31 (35.5%), not requiring O2 on diagnosis (relatively early treatment). Lano et al., 10/21/2020, retrospective, France, Europe, peer-reviewed, median age 73.5, 30 authors.Share Tweet
Submit Corrections or Comments10/21 Late
Dubee et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2021.03.005 (preprint 10/21) (Peer Reviewed) death, ↓46.0%, p=0.21 Hydroxychloroquine in mild-to-moderate COVID-19: a placebo-controlled double blind trial Details Small early terminated late stage (60% on oxygen) RCT in France showing 46% lower mortality. mortality at 28 days relative risk RR 0.54 combined mortality/intubation at 28 days relative risk RR 0.74 If not stoppe.. 10/21 Details SourceLate treatment study Late treatment study Dubee et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2021.03.005 (preprint 10/21) (Peer Reviewed) Hydroxychloroquine in mild-to-moderate COVID-19: a placebo-controlled double blind trial Small early terminated late stage (60% on oxygen) RCT in France showing 46% lower mortality. mortality at 28 days relative risk RR 0.54 combined mortality/intubation at 28 days relative risk RR 0.74 If not stopped early and the same trend continued, statistical significance would be reached on 28 day mortality after ~550 patients (1,300 patients were planned). Mortality results are not provided for subgroups. For the subgroups
receiving AZ:
No safety concerns were identified. This study has been presented as negative, however the results do not support that conclusion.NCT04325893
risk of death at day 28, 46.0% lower, RR 0.54, _p_ = 0.21, treatment 6 of 124 (4.8%), control 11 of 123 (8.9%). risk of combined intubation/death at day 28, 26.0% lower, RR 0.74, _p_ = 0.48, treatment 9 of 124 (7.3%), control 12 of 123 (9.8%). Dubee et al., 10/21/2020, Randomized Controlled Trial, France, Europe, peer-reviewed, median age 77.0, 18 authors.Share Tweet
Submit Corrections or Comments10/21 Late
Ñamendys-Silva et al., Heart & Lung, doi:10.1016/j.hrtlng.2020.10.013 (Peer Reviewed) death, ↓32.3%, p=0.18 Outcomes of patients with COVID-19 in the Intensive Care Unit in Mexico: A multicenter observational study Details Retrospective 164 ICU patients in Mexico showing 32% lower mortality with HCQ+AZ and 37% lower with CQ. HCQ+AZ vs. neither HCQ or CQ relative risk RR 0.68, _p_ = 0.03 CQ vs. neither HCQ or CQ relative risk RR 0.63, _p_ = 0.02 HCQ+AZ or CQ vs.. 10/21 Details SourceLate treatment study Late treatment study Ñamendys-Silva et al., Heart & Lung, doi:10.1016/j.hrtlng.2020.10.013 (Peer Reviewed) Outcomes of patients with COVID-19 in the Intensive Care Unit in Mexico: A multicenter observational study Retrospective 164 ICU patients in Mexico showing 32% lower mortality with HCQ+AZ and 37% lower with CQ. HCQ+AZ vs. neither HCQ or CQ relative risk RR 0.68, _p_ = 0.03 CQ vs. neither HCQ or CQ relative risk RR 0.63, _p_ = 0.02 HCQ+AZ or CQ vs. neither relative risk RR 0.65, _p_ = 0.006 risk of death, 32.3% lower, RR 0.68, _p_ = 0.18, treatment 24 of 54 (44.4%), control 42 of 64 (65.6%), HCQ+AZ vs. neither HCQ or CQ. risk of death, 37.1% lower, RR 0.63, _p_ = 0.09, treatment 19 of 46 (41.3%), control 42 of 64 (65.6%), CQ vs. neither HCQ or CQ. risk of death, 34.5% lower, RR 0.66, _p_ = 0.006, treatment 43 of 100 (43.0%), control 42 of 64 (65.6%), HCQ+AZ or CQ. Ñamendys-Silva et al., 10/21/2020, retrospective, database analysis, Mexico, North America, peer-reviewed, mean age 57.3, 18 authors.
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Submit Corrections or Comments10/20 Early, Late
IHU Marseille (Preprint) (meta analysis - not included in studycount)
meta-analysis
Meta-analysis on chloroquine derivatives and COVID-19 mortality Details Updated meta analysis of 41 studies showing CQ/HCQ OR 0.57, _p_<0.0001 from clinical studies. For big data studies authors find inconsistent results and OR 0.83, _p_=0.0014, and for all studies combined OR 0.72, _p_<0.0001. 10/20 Details SourceEarly, Late
Early, Late
IHU Marseille (Preprint) (meta analysis - not included in studycount)
Meta-analysis on chloroquine derivatives and COVID-19 mortality Updated meta analysis of 41 studies showing CQ/HCQ OR 0.57, _p_<0.0001 from clinical studies. For big data studies authors find inconsistent results and OR 0.83, _p_=0.0014, and for all studies combined OR 0.72, _p_<0.0001. IHU Marseille et al., 10/20/2020, preprint, 1 author.Share Tweet
Submit Corrections or Comments10/20 Late
Solh et al., medRxiv, doi:10.1101/2020.10.16.20214130 (Preprint) death, ↑18.0%, p=0.17 Clinical course and outcome of COVID-19 acute respiratory distress syndrome: data from a national repository Details Retrospective database analysis of 7,816 Veterans Affairs hospitalized patients analyzing progression to ARDS and 30-day mortality from ARDS. Confounding by indication is likely. Chronological bias is likely, with HCQ more likely to be us.. 10/20 Details SourceLate treatment study Late treatment study Solh et al., medRxiv, doi:10.1101/2020.10.16.20214130 (Preprint) Clinical course and outcome of COVID-19 acute respiratory distress syndrome: data from a national repository Retrospective database analysis of 7,816 Veterans Affairs hospitalized patients analyzing progression to ARDS and 30-day mortality from ARDS. Confounding by indication is likely. Chronological bias is likely, with HCQ more likely to be used earlier on, before significant improvements in overall treatment. No results are provided for HCQ for progression to ARDS. risk of death, 18.0% higher, RR 1.18, _p_ = 0.17, treatment 131 of 265 (49.4%), control 134 of 378 (35.4%), adjusted. Solh et al., 10/20/2020, retrospective, database analysis, USA, North America, preprint, 5 authors.
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Submit Corrections or Comments10/17 Early
Mohana et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.031 (preprint 8/17) (Peer Reviewed) (not included in the study count)safety analysis
Hydroxychloroquine Safety Outcome within Approved Therapeutic Protocol for COVID-19 Outpatients in Saudi Arabia Details Safety study of 2,733 patients in Saudi Arabia showing HCQ in mild to moderate cases in an outpatient setting, within the protocol recommendation and inclusion/exclusion criteria, is safe, highly tolerable, and has minimal side effects. N.. 10/17 Details SourceEarly treatment study Early treatment study Mohana et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.031 (preprint 8/17) (Peer Reviewed) (not included in the study count) Hydroxychloroquine Safety Outcome within Approved Therapeutic Protocol for COVID-19 Outpatients in Saudi Arabia Safety study of 2,733 patients in Saudi Arabia showing HCQ in mild to moderate cases in an outpatient setting, within the protocol recommendation and inclusion/exclusion criteria, is safe, highly tolerable, and has minimal side effects. No ICU admission or deaths
were reported.
Mohana et al., 10/17/2020, peer-reviewed, 15 authors.Share Tweet
Submit Corrections or Comments10/15 Late
Guisado-Vasco (Peer Reviewed) death, ↓20.3%, p=0.36 Clinical characteristics and outcomes among hospitalized adults with severe COVID-19 admitted to a tertiary medical center and receiving antiviral, antimalarials, glucocorticoids, or immunomodulation with tocilizumab or cyclosporine: A retrospective observational study (COQUIMA cohort) Details Retrospective 607 patients reporting results for early outpatient HCQ use with mortality odds ratio OR 0.092 , _p_ = 0.001 (65 patients), and for hospital use, mortality odds ratio OR 0.737 , _p_ = 0.36(558 patients)...
10/15 Details SourceLate treatment study Late treatment study Guisado-Vasco (Peer Reviewed) Clinical characteristics and outcomes among hospitalized adults with severe COVID-19 admitted to a tertiary medical center and receiving antiviral, antimalarials, glucocorticoids, or immunomodulation with tocilizumab or cyclosporine: A retrospective observational study (COQUIMA cohort) Retrospective 607 patients reporting results for early outpatient HCQ use with mortality odds ratio OR 0.092 , _p_ = 0.001 (65 patients), and for hospital use, mortality odds ratio OR 0.737 , _p_ = 0.36 (558 patients). Median age 69. risk of death, 20.3% lower, RR 0.80, _p_ = 0.36, treatment 127 of 558 (22.8%), control 14 of 49 (28.6%), adjusted, OR converted to RR. outpatient use, 88.0% lower, RR 0.12, _p_ = 0.001, treatment 2 of 65 (3.1%), control 139 of 542 (25.6%), adjusted, OR converted to RR. Guisado-Vasco et al., 10/15/2020, retrospective, Spain, Europe, peer-reviewed, median age 69.0, 25 authors.
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Submit Corrections or Comments10/15 Late
SOLIDARITY Trial Consortium, NEJM, doi:10.1056/NEJMoa2023184 (preprint 10/15) (Peer Reviewed) death, ↑19.0%, p=0.23 Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITYtrial results
Details WHO SOLIDARITY open-label trial with 954 very late stage (64% on oxygen/ventilation) HCQ patients, mortality relative risk RR 1.19 , _p_=0.23. HCQ dosage very high as in RECOVERY, 1.6g in the first 24 hours, 9.6g total over 10d..
10/15 Details SourceLate treatment study Late treatment study SOLIDARITY Trial Consortium, NEJM, doi:10.1056/NEJMoa2023184 (preprint 10/15) (Peer Reviewed) Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITY
trial results
WHO SOLIDARITY open-label trial with 954 very late stage (64% on oxygen/ventilation) HCQ patients, mortality relative risk RR 1.19, _p_=0.23.
HCQ dosage very high as in RECOVERY, 1.6g in the first 24 hours, 9.6g total over 10 days, only 25% less than the high dosage that Borba et al. show greatly increases risk (OR 2.8) . Authors state they do not know the weight or obesity status of patients to analyze toxicity (since they do not adjust dosage based on patient weight, toxicity may be higher in patients of lower weight). KM curves show a spike in HCQ mortality days 5-7, corresponding to ~90% of the total excess seen at day 28 (a similar spike is seen in the RECOVERY trial). Almost all excess mortality is from ventilated patients. Authors refer to a lack of excess mortality in the first few days to suggest a lack of toxicity, but they are ignoring the very long half-life of HCQ and the dosing regimen - much higher levels of HCQ will be reached later. Increased mortality in Borba et al. occurredafter 2 days.
An unspecified percentage used the more toxic CQ. No placebo used. For more on the dosing problems see , also noting that concentrations vary substantially in different tissues and lung concentration may be >30x plasma concentration. c19study.com/borba.html kristianfranciscomillanielsen.medium.com/analysis-of-the-hydroxychloroquine-dosing-regimen-in-reco.. risk of death, 19.0% higher, RR 1.19, _p_ = 0.23, treatment 104 of 947 (11.0%), control 84 of 906 (9.3%). SOLIDARITY et al., 10/15/2020, Randomized Controlled Trial, multiple countries, multiple regions, peer-reviewed, baseline oxygen requirements 64.0%, 15 authors.Share Tweet
Submit Corrections or Comments10/12 Late
Annie et al., Pharmacotherapy, doi:10.1002/phar.2467 (PeerReviewed)
death, ↓4.3%, p=0.83 Hydroxychloroquine in hospitalized COVID‐19 patients: Real world experience assessing mortality Details Retrospective database analysis with PSM not including COVID-19 severity, finding mortality OR 0.95 for HCQ, and 1.24 for HCQ+AZ. Confounding by indicationlikely.
10/12 Details SourceLate treatment study Late treatment study Annie et al., Pharmacotherapy, doi:10.1002/phar.2467 (Peer
Reviewed)
Hydroxychloroquine in hospitalized COVID‐19 patients: Real world experience assessing mortality Retrospective database analysis with PSM not including COVID-19 severity, finding mortality OR 0.95 for HCQ, and 1.24 for HCQ+AZ. Confounding by indication likely. risk of death, 4.3% lower, RR 0.96, _p_ = 0.83, treatment 48 of 367 (13.1%), control 50 of 367 (13.6%), OR converted to RR. risk of death, 20.5% higher, RR 1.21, _p_ = 0.46, treatment 29 of 199 (14.6%), control 24 of 199 (12.1%), OR converted to RR. Annie et al., 10/12/2020, retrospective, database analysis, USA, North America, peer-reviewed, 5 authors.Share Tweet
Submit Corrections or Comments10/11 Late
Sili et al., medRxiv, doi:10.1101/2020.10.09.20209775 (Preprint) (not included in the study count) Factors associated with progression to critical illness in 28 days among COVID-19 patients: results from a tertiary care hospital inIstanbul, Turkey
Details Analysis of hospitalized patients in Turkey showing HCQ was given to 99.2% of patients and the incidence of critical illness was lower than most studies. Authors note "whether HCQ administration lowered the rates of critical illness .. 10/11 Details SourceLate treatment study Late treatment study Sili et al., medRxiv, doi:10.1101/2020.10.09.20209775 (Preprint) (not included in the study count) Factors associated with progression to critical illness in 28 days among COVID-19 patients: results from a tertiary care hospital in
Istanbul, Turkey
Analysis of hospitalized patients in Turkey showing HCQ was given to 99.2% of patients and the incidence of critical illness was lower than most studies. Authors note "whether HCQ administration lowered the rates of critical illness development is beyond the scope of this study." There is no comparison with a control group. Sili et al., 10/11/2020, Turkey, Middle East, preprint, 21 authors.Share Tweet
Submit Corrections or Comments10/8 Late
Aparisi et al., medRxiv, doi:10.1101/2020.10.06.20207092(Preprint)
death, ↓63.0%, p=0.008 Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19 Details Retrospective 654 hospitalized patients focused on low-density lipoprotein cholesterol levels, also showing results for HCQ with 605 HCQ patients, unadjusted 30 day mortality relative risk RR 0.37, _p_ = 0.008. 10/8 Details SourceLate treatment study Late treatment study Aparisi et al., medRxiv, doi:10.1101/2020.10.06.20207092 (Preprint) Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19 Retrospective 654 hospitalized patients focused on low-density lipoprotein cholesterol levels, also showing results for HCQ with 605 HCQ patients, unadjusted 30 day mortality relative risk RR 0.37, _p_ =
0.008.
risk of death, 63.0% lower, RR 0.37, _p_ = 0.008, treatment 122 of 605 (20.2%), control 27 of 49 (55.1%). Aparisi et al., 10/8/2020, prospective, Spain, Europe, preprint, 18authors.
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Submit Corrections or Comments10/8 Late
Soto-Becerra et al., medRxiv, doi:10.1101/2020.10.06.20208066(Preprint)
death, ↓18.1%, p<0.0001 Real-World Effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: Results of a target trial emulation using observational data from a nationwide HealthcareSystem in Peru
Details Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care. This study includes anyone withICD-10..
10/8 Details SourceLate treatment study Late treatment study Soto-Becerra et al., medRxiv, doi:10.1101/2020.10.06.20208066
(Preprint)
Real-World Effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: Results of a target trial emulation using observational data from a nationwide HealthcareSystem in Peru
Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care. This study includes anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore many patients in the control group are likely asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. For those that had symptomatic COVID-19, there is also likely significant confounding by indication. In this study all medications show higher mortality at day 30, which is consistent with asymptomatic (for COVID-19) or mild condition patients being more common in the control group. For ivermectin they show 30 day mortality aHR = 1.39 . KM curves show that the treatment groups were in more serious condition, and also that after about day 35 survival became better with ivermectin. The last day available for ivermectin shows RR 0.83, _p_ = 0.01. More than the total excess mortality happened on the first day. This is consistent with treated patients being in more serious condition, and with many of the control group patients being in hospital for something unrelated to COVID-19. Authors use a machine learning based propensity scoring system that appears over-parameterized and likely to result in significant overfitting and inaccurate results. Essentially they test for all interactions between two and three covariates. The nature and large number of covariates means many random correlations may be found. COVID-19 severity is not used. This study also does not compare treatments with a control group not receiving the treatment - authors put patients receiving treatments after 48 hours in the control group. Authors state that outcomes within 24 hours were excluded, however KM curves show significant mortality at day 1 (only for the treatmentgroups).
Several protocol violations and missing data have also been reportedin this study: .
See also: .
Ivermectin dosage details: trialsitenews.com/systemic-unreported-protocol-violations-in-key-ivermectin-study/ trialsitenews.com/missing-data-in-soto-becerra-et-al-the-one-study-showing-worse-outcomes-with-ive.. twitter.com/Covid19Crusher/status/1315461049034907650 cdn.www.gob.pe/uploads/document/file/830595/RM_375-2020-MINSA.PDF risk of death, 18.1% lower, RR 0.82, _p_ < 0.001, treatment 346 of 692 (50.0%), control 1606 of 2630 (61.1%), day 54 (last day available)weighted KM.
risk of death, 84.0% higher, RR 1.84, _p_ = 0.02, treatment 165 of 692 (23.8%), control 401 of 2630 (15.2%), adjusted, day 30. Soto-Becerra et al., 10/8/2020, retrospective, database analysis, Peru, South America, preprint, median age 59.4, 4 authors.Share Tweet
Submit Corrections or Comments10/6 Late
Ader et al., medRxiv, doi:10.1101/2021.01.08.20248149 (news 10/6)(Preprint)
death, ↓6.4%, p=1.00 Antiviral drugs in hospitalized patients with COVID-19 - theDisCoVeRy trial
Details Early terminated very late stage (95% on oxygen at baseline) DISCOVERY trial. 4% more patients were on ventilation at baseline in the HCQ group. 10/6 Details SourceLate treatment study Late treatment study Ader et al., medRxiv, doi:10.1101/2021.01.08.20248149 (news 10/6)
(Preprint)
Antiviral drugs in hospitalized patients with COVID-19 - theDisCoVeRy trial
Early terminated very late stage (95% on oxygen at baseline) DISCOVERY trial. 4% more patients were on ventilation at baseline inthe HCQ group.
risk of death at day 29, 6.4% lower, RR 0.94, _p_ = 1.00, treatment 11 of 145 (7.6%), control 12 of 148 (8.1%). Ader et al., 10/6/2020, Randomized Controlled Trial, multiple countries, Europe, preprint, baseline oxygen requirements 95.4%, 52authors.
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Submit Corrections or Comments10/5 Late
Mori et al., Journal of Microbiology, Immunology and Infection, doi:10.1016/j.jmii.2020.09.003 (Peer Reviewed) Triple therapy with hydroxychloroquine, azithromycin, and ciclesonide for COVID-19 pneumonia Details Small case study of 5 patients in Japan showing improvement with HCQ+AZ+ciclesonide. 10/5 Details SourceLate treatment study Late treatment study Mori et al., Journal of Microbiology, Immunology and Infection, doi:10.1016/j.jmii.2020.09.003 (Peer Reviewed) Triple therapy with hydroxychloroquine, azithromycin, and ciclesonide for COVID-19 pneumonia Small case study of 5 patients in Japan showing improvement with
HCQ+AZ+ciclesonide.
Mori et al., 10/5/2020, peer-reviewed, 3 authors.Share Tweet
Submit Corrections or Comments10/5 Early, Late
Prodromos et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100776 (Peer Reviewed) (meta analysis - not included in study count)meta-analysis
Hydroxychloroquine is effective, and consistently so used early, for Covid-19: A systematic review Details Meta analysis of 43 studies: "HCQ was found consistently effective against COVID-19 when used early, in the outpatient setting. It was found overall effective also including inpatient studies. No unbiased study found worse outcomes w.. 10/5 Details SourceEarly, Late
Early, Late
Prodromos et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100776 (Peer Reviewed) (meta analysis - not included in study count) Hydroxychloroquine is effective, and consistently so used early, for Covid-19: A systematic review Meta analysis of 43 studies: "HCQ was found consistently effective against COVID-19 when used early, in the outpatient setting. It was found overall effective also including inpatient studies. No unbiased study found worse outcomes with HCQ use. No mortality or serious safety adverse event was found. Prodromos et al., 10/5/2020, peer-reviewed, 2 authors.Share Tweet
Submit Corrections or Comments10/2 Late
Nachega et al., The American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.20-1240 (Peer Reviewed) death, ↓27.6%, p=0.17 Clinical Characteristics and Outcomes of Patients Hospitalized for COVID-19 in Africa: Early Insights from the Democratic Republic of theCongo
Details Retrospective 766 hospitalized patients in DRC showing mortality reduced from 29% to 11%, and improvement at 30 days increased from 65% to 84%. Mortality cox regression adjusted hazard ratio aHR 0.26, _p_ < 0.001 Risk of no improvement adj.. 10/2 Details SourceLate treatment study Late treatment study Nachega et al., The American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.20-1240 (Peer Reviewed) Clinical Characteristics and Outcomes of Patients Hospitalized for COVID-19 in Africa: Early Insights from the Democratic Republic of the
Congo
Retrospective 766 hospitalized patients in DRC showing mortality reduced from 29% to 11%, and improvement at 30 days increased from 65%to 84%.
Mortality cox regression adjusted hazard ratio aHR 0.26, _p_ < 0.001 Risk of no improvement adjusted odds ratio aOR 0.28, _p_ < 0.001 Using marginal structural model analysis these risks became: Mortality MSM adjusted odds ratio aOR 0.65, _p_ = 0.166 Risk of no improvement MSM adjusted odds ratio aOR = 0.65, _p_ = 0.132 Median age 46, 630 treated with CQ+AZ. risk of death, 27.6% lower, RR 0.72, _p_ = 0.17, treatment 69 of 630 (11.0%), control 28 of 96 (29.2%), adjusted, OR converted to RR. risk of no improvement, 25.8% lower, RR 0.74, _p_ = 0.13, adjusted,OR converted to RR.
Nachega et al., 10/2/2020, retrospective, database analysis, Democratic Republic of Congo, Africa, peer-reviewed, median age 46.0,25 authors.
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Submit Corrections or Comments10/1 Late
Almazrou et al., Saudi Pharmaceutical Journal, doi:10.1016/j.jsps.2020.09.019 (Peer Reviewed) ventilation, ↓65.0%, p=0.16 Comparing the impact of Hydroxychloroquine based regimens and standard treatment on COVID-19 patient outcomes: A retrospectivecohort study
Details Retrospective 161 hospitalized patients in Saudi Arabia showing lower ventilation and ICU admission with HCQ, but not statistically significant with the small samplesizes.
10/1 Details SourceLate treatment study Late treatment study Almazrou et al., Saudi Pharmaceutical Journal, doi:10.1016/j.jsps.2020.09.019 (Peer Reviewed) Comparing the impact of Hydroxychloroquine based regimens and standard treatment on COVID-19 patient outcomes: A retrospective
cohort study
Retrospective 161 hospitalized patients in Saudi Arabia showing lower ventilation and ICU admission with HCQ, but not statistically significant with the small sample sizes. risk of mechanical ventilation, 65.0% lower, RR 0.35, _p_ = 0.16, treatment 3 of 95 (3.2%), control 6 of 66 (9.1%). risk of ICU admission, 21.0% lower, RR 0.79, _p_ = 0.78, treatment 8 of 95 (8.4%), control 7 of 66 (10.6%). Almazrou et al., 10/1/2020, retrospective, Saudi Arabia, Middle East, peer-reviewed, 5 authors.Share Tweet
Submit Corrections or Comments10/1 PrEP, PEP
Garcia-Albeniz et al., medRxiv, doi:10.1101/2020.09.29.20203869 (Preprint) (meta analysis - not included in study count) cases, ↓22.0%, p=0.04 Brief communication: A meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19 Details Combination of the four underpowered prophylaxis RCTs to date showing statistically significant results, RR 0.78 . The actual effect of HCQ is likely to be higher for several reasons: the trials did not adjust forlosses to fo..
10/1 Details SourcePrEP, PEP
PrEP, PEP
Garcia-Albeniz et al., medRxiv, doi:10.1101/2020.09.29.20203869 (Preprint) (meta analysis - not included in study count) Brief communication: A meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19 Combination of the four underpowered prophylaxis RCTs to date showing statistically significant results, RR 0.78 . The actual effect of HCQ is likely to be higher for several reasons: the trials did not adjust for losses to follow-up or other deviations from protocol. There was very long treatment delays in the postexposure prophylaxis trials - in one trial, about a third of participants were enrolled 4 days after exposure with an additional shipping delay of ~46 hours on average, in the other, participants were enrolled up to 7 days after exposure, with an unknown additional delay before treatment, and results suggesting that exposure detectionwas delayed.
For other reasons see: . c19study.com/boulware.html c19study.com/mitjapep.html c19study.com/rajasingham.html c19study.com/abella.html risk of COVID-19 case, 22.0% lower, RR 0.78, _p_ = 0.04. Garcia-Albeniz et al., 10/1/2020, preprint, 5 authors.Share Tweet
Submit Corrections or Comments9/30 PEP
Polat et al., Medical Journal of Bakirkoy, 16:3, 280-6, doi:10.5222/BMJ.2020.50469 (Peer Reviewed) cases, ↓57.0%, p=0.03 Hydroxychloroquine Use on Healthcare Workers Exposed to COVID-19 -A Pandemic Hospital Experience Details Small prophylaxis study of 208 healthcare workers in Turkey, 138 with high risk exposure received HCQ, while 70 with low and medium risk exposure did not. COVID-19 cases were lower in the treatment group, relative risk RR 0.43, _p_ = 0.026... 9/30 Details SourcePost Exposure Prophylaxis study Post Exposure Prophylaxis study Polat et al., Medical Journal of Bakirkoy, 16:3, 280-6, doi:10.5222/BMJ.2020.50469 (Peer Reviewed) Hydroxychloroquine Use on Healthcare Workers Exposed to COVID-19 -A Pandemic Hospital Experience Small prophylaxis study of 208 healthcare workers in Turkey, 138 with high risk exposure received HCQ, while 70 with low and medium risk exposure did not. COVID-19 cases were lower in the treatment group, relative risk RR 0.43, _p_ = 0.026. Since the control group had lower risk, the actual benefit may be larger. risk of COVID-19 case, 57.0% lower, RR 0.43, _p_ = 0.03, treatment 12 of 138 (8.7%), control 14 of 70 (20.0%). Polat et al., 9/30/2020, prospective, Turkey, Middle East, peer-reviewed, 3 authors.
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Submit Corrections or Comments9/30 Late
Ayerbe et al., Internal and Emergency Medicine, doi:0.1007/s11739-020-02505-x (Peer Reviewed) death, ↓52.2%, p<0.001 The association of treatment with hydroxychloroquine and hospital mortality in COVID-19 patients Details 2075 hospital patients in Spain showing HCQ reduces mortality 52%, odds ratio OR 0.39, _p_<0.001, after adjustment for age, gender, temperature > 37 °C, and saturation of oxygen < 90% treatment with azithromycin, steroids, heparin,tocilizu..
9/30 Details SourceLate treatment study Late treatment study Ayerbe et al., Internal and Emergency Medicine, doi:0.1007/s11739-020-02505-x (Peer Reviewed) The association of treatment with hydroxychloroquine and hospital mortality in COVID-19 patients 2075 hospital patients in Spain showing HCQ reduces mortality 52%, odds ratio OR 0.39, _p_<0.001, after adjustment for age, gender, temperature > 37 °C, and saturation of oxygen < 90% treatment with azithromycin, steroids, heparin, tocilizumab, a combination of lopinavir with ritonavir, and oseltamivir, and date of admission
(model 4).
risk of death, 52.2% lower, RR 0.48, _p_ < 0.001, treatment 237 of 1857 (12.8%), control 49 of 162 (30.2%), adjusted, OR converted to RR. Ayerbe et al., 9/30/2020, retrospective, database analysis, Spain, Europe, peer-reviewed, 3 authors.Share Tweet
Submit Corrections or Comments 9/30 PrEP, PEP, Early Ladapo et al., medRxiv, doi:10.1101/2020.09.30.20204693 (Preprint) (meta analysis - not included in study count) cases/death/hosp., ↓24.0%, p=0.03 Randomized Controlled Trials of Early Ambulatory Hydroxychloroquine in the Prevention of COVID-19 Infection, Hospitalization, and Death:Meta-Analysis
Details Meta analysis of prophylactic and early treatment RCTs, 24% reduction in cases, hospitalization or death with HCQ, RR 0.76, _p_=0.025. No serious adverse cardiac events were reported. 5,577 patients. The Boulware study provides a breakdown.. 9/30 Details SourcePrEP, PEP, Early
PrEP, PEP, Early
Ladapo et al., medRxiv, doi:10.1101/2020.09.30.20204693 (Preprint) (meta analysis - not included in study count) Randomized Controlled Trials of Early Ambulatory Hydroxychloroquine in the Prevention of COVID-19 Infection, Hospitalization, and Death:Meta-Analysis
Meta analysis of prophylactic and early treatment RCTs, 24% reduction in cases, hospitalization or death with HCQ, RR 0.76, _p_=0.025. No serious adverse cardiac events were reported. 5,577 patients. The Boulware study provides a breakdown for treatment delay. For the case of < ~4 days (2 days enrollment, ~46 hours shipping), the result of the meta analysis becomes RR 0.68, _p_=0.0097. The actual effect may be larger due to treatment delays, followup loss, protocol deviation, active placebos, no severity analysis for cases, and suboptimal regimens. For the individual studies see . c19study.com/boulware.html c19study.com/mitjapep.html c19study.com/rajasingham.html c19study.com/skipper.html c19study.com/mitja.html risk of combined cases/death/hospitalization, 24.0% lower, RR 0.76,_p_ = 0.03.
Ladapo et al., 9/30/2020, preprint, 4 authors.Share Tweet
Submit Corrections or Comments9/30 PrEP
Abella et al., JAMA Internal Medicine, doi:doi:10.1001/jamainternmed.2020.6319 (Peer Reviewed) cases, ↓5.0%, p=1.00 Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers Details Very small early-terminated underpowered PrEP RCT with 64/61 HCQ/control patients and only 8 infections, HCQ infection rate 6.3% versus control 6.6%, RR 0.95 . There was no hospitalization or death, no significant difference.. 9/30 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Abella et al., JAMA Internal Medicine, doi:doi:10.1001/jamainternmed.2020.6319 (Peer Reviewed) Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers Very small early-terminated underpowered PrEP RCT with 64/61 HCQ/control patients and only 8 infections, HCQ infection rate 6.3% versus control 6.6%, RR 0.95 . There was no hospitalization or death, no significant difference in QTc, no severe adverse events, no cardiac events (e.g., syncope and arrhythmias) observed. Medication adherence was 81%. Therapeutic levels of HCQ may not have been reached by the time of the infection
in the first week.
2 infections were reported to be after discontinuation of the medication, but the authors do not specify which arm these were in. Hypothetically, if these were both in the HCQ arm, the resulting RR for treatment would be much lower. risk of COVID-19 case, 5.0% lower, RR 0.95, _p_ = 1.00, treatment 4 of 64 (6.2%), control 4 of 61 (6.6%). Abella et al., 9/30/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 18 authors.Share Tweet
Submit Corrections or Comments9/29 Late
Lammers et al., Int. J. Infectious Diseases, doi:10.1016/j.ijid.2020.09.1460 (Peer Reviewed) death/ICU, ↓32.0%, p=0.02 Early hydroxychloroquine but not chloroquine use reduces ICU admission in COVID-19 patients Details Observational study 1,064 hospitalized patients in the Netherlands, 53% reduced risk of transfer to the ICU for mechanical ventilation with HCQ treatment starting on the first day of admission. Weighted propensity score adjusted hazard r.. 9/29 Details SourceLate treatment study Late treatment study Lammers et al., Int. J. Infectious Diseases, doi:10.1016/j.ijid.2020.09.1460 (Peer Reviewed) Early hydroxychloroquine but not chloroquine use reduces ICU admission in COVID-19 patients Observational study 1,064 hospitalized patients in the Netherlands, 53% reduced risk of transfer to the ICU for mechanical ventilation with HCQ treatment starting on the first day of admission. Weighted propensity score adjusted hazard ratio for transfer to the ICU with HCQ treatment, HR = 0.47, _p_ = 0.008. For CQ, HR = 0.8, _p_ = 0.207. Mortality results in this study are only for mortality before transfer to the ICU. The combined ICU/death HR was 0.68, _p_ = 0.024 for HCQ, and 0.85, _p_ = 0.224 for CQ. Observational, multicenter, cohort study of hospitalized COVID-19 patients. 189 HCQ patients, 377 CQ, 498 control. risk of combined death/ICU, 32.0% lower, RR 0.68, _p_ = 0.02, treatment 30 of 189 (15.9%), control 101 of 498 (20.3%), adjusted. Lammers et al., 9/29/2020, prospective, Netherlands, Europe, peer-reviewed, 18 authors.
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Submit Corrections or Comments9/29 Late
Dabbous et al., Research Square, doi:10.21203/rs.3.rs-83677/v1(Preprint)
A Randomized Controlled Study Of Favipiravir Vs Hydroxychloroquine In COVID-19 Management: What Have We Learned So Far? Details Small RCT comparing HCQ and favipiravir, with 50 patients in each arm, finding that 55.1% of HCQ patients were PCR negative on day 7 compared to 48% for favipiravir, _p_ = 0.7. There was no comparison with a control group. 9/29 Details SourceLate treatment study Late treatment study Dabbous et al., Research Square, doi:10.21203/rs.3.rs-83677/v1
(Preprint)
A Randomized Controlled Study Of Favipiravir Vs Hydroxychloroquine In COVID-19 Management: What Have We Learned So Far? Small RCT comparing HCQ and favipiravir, with 50 patients in each arm, finding that 55.1% of HCQ patients were PCR negative on day 7 compared to 48% for favipiravir, _p_ = 0.7. There was no comparison with a control group. Dabbous et al., 9/29/2020, preprint, 11 authors.Share Tweet
Submit Corrections or Comments9/28 PEP
Luco, J., Trends Med, doi:10.15761/TiM.1000268 (Peer Reviewed) (meta analysis - not included in study count)meta-analysis
Hydroxychloroquine as post-exposure prophylaxis for Covid-19: Why simple data analysis can lead to the wrong conclusions from well-designed studies Details Reanalysis of Boulware et al. PEP trial data showing statistically significant improvements with HCQ. 9/28 Details SourcePost Exposure Prophylaxis study Post Exposure Prophylaxis study Luco, J., Trends Med, doi:10.15761/TiM.1000268 (Peer Reviewed) (meta analysis - not included in study count) Hydroxychloroquine as post-exposure prophylaxis for Covid-19: Why simple data analysis can lead to the wrong conclusions from well-designed studies Reanalysis of Boulware et al. PEP trial data showing statistically significant improvements with HCQ. Luco et al., 9/28/2020, peer-reviewed, 1 author.
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Submit Corrections or Comments9/24 Early, Late
Gasperetti et al., EP Europace, doi:10.1093/europace/euaa216 (Peer Reviewed) (not included in the study count)safety analysis
Arrhythmic safety of hydroxychloroquine in COVID-19 patients from different clinical settings Details Safety study of 649 patients finding that HCQ administration is safe for short-term treatment for patients with COVID-19 infection regardless of the clinical setting of delivery, causing only modest QTc prolongation and no directlyattrib..
9/24 Details SourceEarly, Late
Early, Late
Gasperetti et al., EP Europace, doi:10.1093/europace/euaa216 (Peer Reviewed) (not included in the study count) Arrhythmic safety of hydroxychloroquine in COVID-19 patients from different clinical settings Safety study of 649 patients finding that HCQ administration is safe for short-term treatment for patients with COVID-19 infection regardless of the clinical setting of delivery, causing only modest QTc prolongation and no directly attributable arrhythmic deaths. Arrhythmic safety data from a large cohort of patients treated with HCQ alone or in combination with other QT-prolonging drugs. Gasperetti et al., 9/24/2020, peer-reviewed, 23 authors.Share Tweet
Submit Corrections or Comments9/24 Late
Shoaibi et al., medRxiv, doi:10.1101/2020.09.23.20199463(Preprint)
death, ↓15.4%, p<0.001 Comparative Effectiveness of Famotidine in Hospitalized COVID-19Patients
Details Retrospective database analysis focused on Famotidine but also showing results for HCQ users, with unadjusted mortality RR 0.85, _p_<0.001 (13.6% vs. 16.1%). 9/24 Details SourceLate treatment study Late treatment study Shoaibi et al., medRxiv, doi:10.1101/2020.09.23.20199463 (Preprint) Comparative Effectiveness of Famotidine in Hospitalized COVID-19
Patients
Retrospective database analysis focused on Famotidine but also showing results for HCQ users, with unadjusted mortality RR 0.85, _p_<0.001 (13.6% vs. 16.1%). risk of death, 15.4% lower, RR 0.85, _p_ < 0.001, treatment 686 of 5047 (13.6%), control 3923 of 24404 (16.1%). Shoaibi et al., 9/24/2020, retrospective, database analysis, USA, North America, preprint, 5 authors.Share Tweet
Submit Corrections or Comments9/23 Late
Ulrich et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa446 (Peer Reviewed) death, ↑6.0%, p=1.00 Treating Covid-19 With Hydroxychloroquine (TEACH): A Multicenter, Double-Blind, Randomized Controlled Trial in Hospitalized Patients Details Small RCT on very late stage use of HCQ, with 48% on oxygen at baseline. 67 HCQ patients, 61 control. Baseline states were not comparable - 82% more HCQ patients had the highest severity at baseline, there was 32% more male HCQ patients,.. 9/23 Details SourceLate treatment study Late treatment study Ulrich et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa446 (Peer Reviewed) Treating Covid-19 With Hydroxychloroquine (TEACH): A Multicenter, Double-Blind, Randomized Controlled Trial in Hospitalized Patients Small RCT on very late stage use of HCQ, with 48% on oxygen at baseline. 67 HCQ patients, 61 control. Baseline states were not comparable - 82% more HCQ patients had the highest severity at baseline, there was 32% more male HCQ patients, and 44% more control patients used AZ. The HCQ group also had significantly more patients with cerebrovascular disease, cardiovascular disease (non-hypertension), renal disease (non-dialysis), and a history of organ transplants. 30 day mortality RR 1.06, _p_ = 1.0. risk of death, 6.0% higher, RR 1.06, _p_ = 1.00, treatment 7 of 67 (10.4%), control 6 of 61 (9.8%). Ulrich et al., 9/23/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, baseline oxygen requirements 63.3%, mean age
66.2, 18 authors.
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Submit Corrections or Comments9/22 Late
Serrano et al., Ann. Oncol., 2020, Sep, 31, S1026, doi:10.1016/j.annonc.2020.08.1830 (Peer Reviewed) death, ↓43.0%, p=0.14 COVID-19 and lung cancer: What do we know? Details Small retrospective study of 22 lung cancer patients, 14 treated with HCQ+AZ, showing HCQ+AZ mortality relative risk RR 0.57, _p_ = 0.145. 9/22 Details SourceLate treatment study Late treatment study Serrano et al., Ann. Oncol., 2020, Sep, 31, S1026, doi:10.1016/j.annonc.2020.08.1830 (Peer Reviewed) COVID-19 and lung cancer: What do we know? Small retrospective study of 22 lung cancer patients, 14 treated with HCQ+AZ, showing HCQ+AZ mortality relative risk RR 0.57, _p_ = 0.145. risk of death, 43.0% lower, RR 0.57, _p_ = 0.14, treatment 6 of 14 (42.9%), control 6 of 8 (75.0%). Serrano et al., 9/22/2020, retrospective, Spain, Europe, peer-reviewed, 8 authors.
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Submit Corrections or Comments9/21 PrEP
Gentry et al., Lancet Rheumatology, doi:10.1016/S2665-9913(20)30305-2 (Peer Reviewed) death, ↓91.3%, p=0.10 Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospectivecohort study
Details Retrospective patients with rheumatologic conditions showing zero of 10,703 COVID-19 deaths for HCQ patients versus 7 of 21,406 propensity matched control patients (not statistically significant). The average age of HCQ patients isslight..
9/21 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Gentry et al., Lancet Rheumatology, doi:10.1016/S2665-9913(20)30305-2 (Peer Reviewed) Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective
cohort study
Retrospective patients with rheumatologic conditions showing zero of 10,703 COVID-19 deaths for HCQ patients versus 7 of 21,406 propensity matched control patients (not statistically significant). The average age of HCQ patients is slightly lower 64.8 versus 65.4 control. COVID-19 cases OR 0.79, _p_=0.27. There are several significant differences in the propensity matched patients that could affect results, e.g., 20.9% SLE versus 24.7%. risk of death, 91.3% lower, RR 0.09, _p_ = 0.10, treatment 0 of 10703 (0.0%), control 7 of 21406 (0.0%), continuity correction due to zero event, COVID-19 mortality within all patients. risk of death, 90.7% lower, RR 0.09, _p_ = 0.19, treatment 0 of 31 (0.0%), control 7 of 78 (9.0%), continuity correction due to zero event, mortality for infected patients. risk of COVID-19 case, 20.9% lower, RR 0.79, _p_ = 0.27, treatment 31 of 10703 (0.3%), control 78 of 21406 (0.4%), OR converted to RR. Gentry et al., 9/21/2020, retrospective, database analysis, USA, North America, peer-reviewed, 6 authors.Share Tweet
Submit Corrections or Comments9/21 PrEP
Rajasingham et al., medRxiv, doi:10.1101/2020.09.18.20197327 (PeerReviewed)
cases, ↓27.0%, p=0.12 Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial Details PrEP RCT showing HR 0.73, _p_ = 0.12. Trial halted after 47% enrollment, _p_ < 0.05 will be reached at ~75% enrollment if similar results continue. Trial halted due to low enrollment. US prescriptions only stopped briefly, resuming in June,..
9/21 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Rajasingham et al., medRxiv, doi:10.1101/2020.09.18.20197327 (Peer
Reviewed)
Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial PrEP RCT showing HR 0.73, _p_ = 0.12. Trial halted after 47% enrollment, _p_ < 0.05 will be reached at ~75% enrollment if similar results continue. Trial halted due to low enrollment. US prescriptions only stopped briefly, resuming in June, so the authors can complete the study . HR 0.66/0.68 for full medication adherence, 0.72/0.74, _p_ = 0.18/0.22 overall (1x/2x dosing). Efficacy for first responders was higher, OR 0.32, _p_ = 0.01. First responders had a much higher incidence, allowing greater power, and reducing the effect of confounders such as misdiagnosis of other conditions or survey issues. Performance is similar to placebo for the first 3 weeks. The effect may be greater with a dosage regimen that achieves therapeutic levels faster . ~40% of participants suspected they might have had COVID-19 before the trial, the effect in people without prior COVID-19may be higher.
Authors note:
- the trial was underpowered - investigation into more frequent dosing may be warranted - insufficient dosing with no participants achieving more than the _invitro_ EC50
Internet survey RCT subject to survey bias. There were no deaths or ICU admissions. Low risk healthcare workers, median age ~40. 494 1x/week dosing, 495 2x/week dosing, 494 control participants (1x and 2x participants received the same overall dosage). wattsupwiththat.com/2020/08/24/hydroxychloroquine-in-covid-19-treatment-actual-usage-in-the-usa/ tandfonline.com/doi/full/10.1080/00498254.2020.1824301 risk of hospitalization, 50.1% lower, RR 0.50, _p_ = 1.00, treatment 1 of 989 (0.1%), control 1 of 494 (0.2%). risk of COVID-19 case, 27.0% lower, RR 0.73, _p_ = 0.12, treatment 58 of 989 (5.9%), control 39 of 494 (7.9%). Rajasingham et al., 9/21/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 22 authors.Share Tweet
Submit Corrections or Comments9/21 PrEP
Grau-Pujol et al., Research Square, doi:10.21203/rs.3.rs-72132/v1(Preprint)
cases, ↓67.9%, p=0.47 Pre-exposure prophylaxis with hydroxychloroquine for COVID-19: initial results of a double-blind, placebo-controlled randomizedclinical trial
Details Small PrEP RCT showing that PrEP with HCQ is safe at the dosage used. No deaths, hospitalizations, or serious adverse events. With only one case (in the placebo arm), efficacy was not evaluated. The abstract appears to have a typo anddo..
9/21 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Grau-Pujol et al., Research Square, doi:10.21203/rs.3.rs-72132/v1
(Preprint)
Pre-exposure prophylaxis with hydroxychloroquine for COVID-19: initial results of a double-blind, placebo-controlled randomizedclinical trial
Small PrEP RCT showing that PrEP with HCQ is safe at the dosage used. No deaths, hospitalizations, or serious adverse events. With only one case (in the placebo arm), efficacy was not evaluated. The abstract appears to have a typo and does not match the results section. We believe the results section is correct with one case in the control arm - the 0.8% matches the percentage for the control arm (there is no possible number of cases for the combined arms that matches 0.8%). Note that table 2 refers to risk factors, not outcomes. A previous version of this paper was posted 9/21/20 . researchsquare.com/article/rs-72132/v1 risk of COVID-19 case, 67.9% lower, RR 0.32, _p_ = 0.47, treatment 0 of 142 (0.0%), control 1 of 127 (0.8%), continuity correction due tozero event.
Grau-Pujol et al., 9/21/2020, Randomized Controlled Trial, Spain, Europe, preprint, 22 authors.Share Tweet
Submit Corrections or Comments9/21 Early
Lofgren et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa500 (preprint 9/21) (Peer Reviewed) (not includedin the study count)
safety analysis
Safety of Hydroxychloroquine among Outpatient Clinical Trial Participants for COVID-19 Details Analysis of 2,795 outpatients not showing significant safety concerns with HCQ. No deaths were related to HCQ. There was one serious event requiring hospitalization, identical to the frequency with placebo. 9/21 Details SourceEarly treatment study Early treatment study Lofgren et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa500 (preprint 9/21) (Peer Reviewed) (not included
in the study count)
Safety of Hydroxychloroquine among Outpatient Clinical Trial Participants for COVID-19 Analysis of 2,795 outpatients not showing significant safety concerns with HCQ. No deaths were related to HCQ. There was one serious event requiring hospitalization, identical to the frequency with placebo. Lofgren et al., 9/21/2020, peer-reviewed, 26 authors.Share Tweet
Submit Corrections or Comments9/18 Late
Axfors et al., Nature, doi:10.1038/s41467-021-22446-z (Peer Reviewed) (meta analysis - not included in study count)meta-analysis
Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis ofrandomized trials
Details Meta analysis assigning 89% weight to the RECOVERY and SOLIDARITY trials, producing the same result. These trials used excessively high non-patient-customized dosage in very sick late stage patients, results are not generalizable to typic.. 9/18 Details SourceLate treatment study Late treatment study Axfors et al., Nature, doi:10.1038/s41467-021-22446-z (Peer Reviewed) (meta analysis - not included in study count) Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of
randomized trials
Meta analysis assigning 89% weight to the RECOVERY and SOLIDARITY trials, producing the same result. These trials used excessively high non-patient-customized dosage in very sick late stage patients, results are not generalizable to typical dosage or earlier treatment. For CQ, this study assigns 97% weight to Borba et al., however this study does not have a control group, comparing two different dosagesof CQ.
Of the 29 early treatment trials (including 6 RCTs), authors include the results of only one where they include a non-hospitalized death. Axfors et al., 9/18/2020, peer-reviewed, 97 authors.Share Tweet
Submit Corrections or Comments9/16 N/A
Karatza et al., Xenobiotica (Peer Reviewed) (not included in thestudy count)
dosing study
Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature andsimulations
Details Analysis of HCQ dosing, suggesting that high initial doses followed by low and sparse doses may offer significant benefits to patients by decreasing the viral load without reaching levels considered to produce adverse effects. For instan.. 9/16 Details SourceN/A
N/A
Karatza et al., Xenobiotica (Peer Reviewed) (not included in thestudy count)
Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature andsimulations
Analysis of HCQ dosing, suggesting that high initial doses followed by low and sparse doses may offer significant benefits to patients by decreasing the viral load without reaching levels considered to produce adverse effects. For instance, the dosing scheme proposed for a 70kg adult with moderate COVID-19 symptoms would be 600mg upon diagnosis, 400mg after 12h, 300mg after 24h, 200mg after 36h, followed by 200mg BID for 4 days, followed by 200mg OD for 5 days. Suboptimal dosing regimens that do not fully account for the long half-life of HCQ or the patient characteristics are likely contribute to either limited efficacy where therapeutic levels take too long to reach, or significant adverse effects due to excessive dosage. Karatza et al., 9/16/2020, peer-reviewed, 4 authors.Share Tweet
Submit Corrections or Comments9/15 Late
Ashinyo et al., Pan African Medical Journal, 37:1, doi:10.11604/pamj.supp.2020.37.1.25718 (Peer Reviewed) hosp. time, ↓33.0%, p=0.03 Clinical characteristics, treatment regimen and duration of hospitalization among COVID-19 patients in Ghana: a retrospectivecohort study
Details Retrospective 307 hospital patients in Ghana showing 33% reduction in hospitalization time with HCQ, 29% reduction with HCQ+AZ, and 37% reduction with CQ+AZ. 9/15 Details SourceLate treatment study Late treatment study Ashinyo et al., Pan African Medical Journal, 37:1, doi:10.11604/pamj.supp.2020.37.1.25718 (Peer Reviewed) Clinical characteristics, treatment regimen and duration of hospitalization among COVID-19 patients in Ghana: a retrospective
cohort study
Retrospective 307 hospital patients in Ghana showing 33% reduction in hospitalization time with HCQ, 29% reduction with HCQ+AZ, and 37% reduction with CQ+AZ. hospitalization time, 33.0% lower, relative time 0.67, _p_ = 0.03, treatment 61, control 61. Ashinyo et al., 9/15/2020, retrospective, Ghana, Africa, peer-reviewed, 16 authors.Share Tweet
Submit Corrections or Comments9/14 Late
Lauriola et al., Clinical and Translational Science, doi:10.1111/cts.12860 (Peer Reviewed) death, ↓73.5%, p<0.001 Effect of combination therapy of hydroxychloroquine and azithromycin on mortality in COVID‐19 patients Details Retrospective 377 patients, 73% reduction in mortality with HCQ+AZ, adjusted hazard ratio HR 0.27 . Mean age 71.8. No serious adverse events. Subject to incomplete adjustment for confounders. 9/14 Details SourceLate treatment study Late treatment study Lauriola et al., Clinical and Translational Science, doi:10.1111/cts.12860 (Peer Reviewed) Effect of combination therapy of hydroxychloroquine and azithromycin on mortality in COVID‐19 patients Retrospective 377 patients, 73% reduction in mortality with HCQ+AZ, adjusted hazard ratio HR 0.27 . Mean age 71.8. No serious adverse events. Subject to incomplete adjustment for confounders. risk of death, 73.5% lower, RR 0.27, _p_ < 0.001, treatment 102 of 297 (34.3%), control 35 of 63 (55.6%), adjusted. Lauriola et al., 9/14/2020, retrospective, Italy, Europe, peer-reviewed, mean age 71.8, 10 authors.
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Submit Corrections or Comments9/13 Early
Sulaiman et al., medRxiv, doi:10.1101/2020.09.09.20184143(Preprint)
death, ↓63.7%, p=0.01 The Effect of Early Hydroxychloroquine-based Therapy in COVID-19 Patients in Ambulatory Care Settings: A Nationwide Prospective CohortStudy
Details Observational prospective 5,541 patients, adjusted HCQ mortality odds ratio OR 0.36, _p_ = 0.012. Adjusted hospitalization OR 0.57, _p_ < 0.001. Zinc supplementation was used in all cases. Early treatment in ambulatory fever clinics inSaudi ..
9/13 Details SourceEarly treatment study Early treatment study Sulaiman et al., medRxiv, doi:10.1101/2020.09.09.20184143
(Preprint)
The Effect of Early Hydroxychloroquine-based Therapy in COVID-19 Patients in Ambulatory Care Settings: A Nationwide Prospective CohortStudy
Observational prospective 5,541 patients, adjusted HCQ mortality odds ratio OR 0.36, _p_ = 0.012. Adjusted hospitalization OR 0.57, _p_ < 0.001. Zinc supplementation was used in all cases. Early treatment in ambulatory fever clinics in Saudi Arabia. risk of death, 63.7% lower, RR 0.36, _p_ = 0.01, treatment 7 of 1817 (0.4%), control 54 of 3724 (1.5%), adjusted, OR converted to RR. risk of hospitalization, 38.6% lower, RR 0.61, _p_ = 0.001, treatment 171 of 1817 (9.4%), control 617 of 3724 (16.6%), adjusted, ORconverted to RR.
Sulaiman et al., 9/13/2020, prospective, Saudi Arabia, Middle East, preprint, 22 authors, dosage 400mg bid day 1, 200mg bid days 2-5.Share Tweet
Submit Corrections or Comments9/12 Late
Heberto et al., IJC Heart & Vasculature, doi:10.1016/j.ijcha.2020.100638 (Peer Reviewed) death, ↓53.6%, p=0.04 Implications of myocardial injury in Mexican hospitalized patients with coronavirus disease 2019 (COVID-19) Details Observational prospective 254 hospitalized patients, HCQ+AZ mortality odds ratio OR 0.36, _p_ = 0.04. Ventilation OR 0.20, _p_ = 0.008. 9/12 Details SourceLate treatment study Late treatment study Heberto et al., IJC Heart & Vasculature, doi:10.1016/j.ijcha.2020.100638 (Peer Reviewed) Implications of myocardial injury in Mexican hospitalized patients with coronavirus disease 2019 (COVID-19) Observational prospective 254 hospitalized patients, HCQ+AZ mortality odds ratio OR 0.36, _p_ = 0.04. Ventilation OR 0.20, _p_ = 0.008. risk of death, 53.6% lower, RR 0.46, _p_ = 0.04, treatment 139, control 115, OR converted to RR. risk of mechanical ventilation, 65.6% lower, RR 0.34, _p_ = 0.008, OR
converted to RR.
Heberto et al., 9/12/2020, prospective, Mexico, North America, peer-reviewed, 8 authors.Share Tweet
Submit Corrections or Comments9/9 Late
Alamdari et al., Tohoku J. Exp. Med., 2020, 252, 73-84, doi:10.1620/tjem.252.73 (Peer Reviewed) death, ↓55.0%, p=0.03 Mortality Risk Factors among Hospitalized COVID-19 Patients in a Major Referral Center in Iran Details Retrospective 459 patients in Iran 93% using HCQ, showing HCQ mortality RR 0.45, _p_ = 0.028. HCQ was the only antiviral that showed a significant difference. Small number of control patients and subject to confounding by indication. Averag.. 9/9 Details SourceLate treatment study Late treatment study Alamdari et al., Tohoku J. Exp. Med., 2020, 252, 73-84, doi:10.1620/tjem.252.73 (Peer Reviewed) Mortality Risk Factors among Hospitalized COVID-19 Patients in a Major Referral Center in Iran Retrospective 459 patients in Iran 93% using HCQ, showing HCQ mortality RR 0.45, _p_ = 0.028. HCQ was the only antiviral that showed a significant difference. Small number of control patients and subject to confounding by indication. Average admission delay 5.72 days. risk of death, 55.0% lower, RR 0.45, _p_ = 0.03, treatment 427,
control 32.
Alamdari et al., 9/9/2020, retrospective, Iran, West Asia, peer-reviewed, 14 authors.Share Tweet
Submit Corrections or Comments9/9 Early, Late
Kirenga et al., BMJ Open Respiratory Research, doi:10.1136/bmjresp-2020-000646 (Peer Reviewed) recov. time, ↓25.6%, p=0.20 Characteristics and outcomes of admitted patients infected with SARS-CoV-2 in Uganda Details Prospective 56 patients in Uganda, 29 HCQ and 27 control, showing 25.6% faster recovery with HCQ, 6.4 vs. 8.6 days (_p_ = 0.20). There was no ICU admission, mechanical ventilation, or death. Treatment delay is not specified but at least a..
9/9 Details SourceEarly, Late
Early, Late
Kirenga et al., BMJ Open Respiratory Research, doi:10.1136/bmjresp-2020-000646 (Peer Reviewed) Characteristics and outcomes of admitted patients infected with SARS-CoV-2 in Uganda Prospective 56 patients in Uganda, 29 HCQ and 27 control, showing 25.6% faster recovery with HCQ, 6.4 vs. 8.6 days (_p_ = 0.20). There was no ICU admission, mechanical ventilation, or death. Treatment delay is not specified but at least a portion of patients appear to have been treated early. median time to recovery, 25.6% lower, relative time 0.74, _p_ = 0.20, treatment 29, control 27. Kirenga et al., 9/9/2020, prospective, Uganda, Africa, peer-reviewed, 29 authors, dosage not specified.Share Tweet
Submit Corrections or Comments9/9 PrEP
Rentsch et al., The Lancet Rheumatology, doi:10.1016/S2665-9913(20)30378-7 (preprint 9/9, https://www.medrxiv.org/content/10.1101/2020.09.04.20187781v1) (PeerReviewed)
death, ↑3.0%, p=0.83 Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELYplatform
Details Observational database study of RA/SLE patients in the UK, 194,637 RA/SLE patients with 30,569 having >= 2 HCQ prescriptions in the prior 6 months, HCQ HR 1.03 (HR 0.78 before adjustments). 70 patients with HCQ prescriptions .. 9/9 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Rentsch et al., The Lancet Rheumatology, doi:10.1016/S2665-9913(20)30378-7 (preprint 9/9, https://www.medrxiv.org/content/10.1101/2020.09.04.20187781v1) (Peer
Reviewed)
Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELYplatform
Observational database study of RA/SLE patients in the UK, 194,637 RA/SLE patients with 30,569 having >= 2 HCQ prescriptions in the prior 6 months, HCQ HR 1.03 (HR 0.78 before adjustments). 70 patients with HCQ prescriptions died. One major problem is that there is no knowlege of medication adherence for these 70 - for example, it is possible that they were part of the expected percentage of patients that did not take the medication as prescribed, invalidating the result. Other limitations include confounding by use of bDMARDs and confounding by severity of rheumatological disease. risk of death, 3.0% higher, RR 1.03, _p_ = 0.83, adjusted. Rentsch et al., 9/9/2020, retrospective, population-based cohort, database analysis, United Kingdom, Europe, peer-reviewed, 34 authors.Share Tweet
Submit Corrections or Comments9/9 PrEP
Laplana et al., PLOS ONE, doi:10.1371/journal.pone.0243598 (PeerReviewed)
cases, ↑56.0%, p=0.24 Lack of protective effect of chloroquine derivatives on COVID-19 disease in a Spanish sample of chronically treated patients Details Survey of 319 autoimmune disease patients taking CQ/HCQ with 5.3% COVID-19 incidence, compared to a control group from the general population (matched on age, sex, and region, but not adjusted for autoimmune disease), with 3.4%incidence...
9/9 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Laplana et al., PLOS ONE, doi:10.1371/journal.pone.0243598 (Peer
Reviewed)
Lack of protective effect of chloroquine derivatives on COVID-19 disease in a Spanish sample of chronically treated patients Survey of 319 autoimmune disease patients taking CQ/HCQ with 5.3% COVID-19 incidence, compared to a control group from the general population (matched on age, sex, and region, but not adjusted for autoimmune disease), with 3.4% incidence. It not clear why authors did not compare with autoimmune patients not on CQ/HCQ. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, _p_<0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. If we adjust for the different baseline risk, the result becomes RR 0.36, _p_<0.001, suggesting a substantial benefit for HCQ/CQ treatment (as shown in other studies). There may also be significant survey bias - those experiencing COVID-19 may be more likely to respond to the survey. Authors note that they "could not eliminate completely the possibility of some bias due to the intrinsic condition of the individuals within the treatment group that are undergoing chloroquine or derivative drug treatment due to other diseases that alter their health status and may have different comorbidities", however they could account for one significant bias by comparing with matched autoimmune diseasepatients.
c19study.com/ferri.html risk of COVID-19 case, 56.0% higher, RR 1.56, _p_ = 0.24, treatment 17 of 319 (5.3%), control 11 of 319 (3.4%). Laplana et al., 9/9/2020, retrospective, Spain, Europe, peer-reviewed, survey, 3 authors.Share Tweet
Submit Corrections or Comments9/7 Review
IHU, Expert Review of Clinical Immunology (Review) (Peer Reviewed) (not included in the study count)review
Natural history and therapeutic options for COVID-19 Details Review of the current state of knowledge regarding the natural history of and therapeutic options for COVID-19. Treatment with an oral combination of hydroxychloroquine, azithromycin and zinc may represent the best current therapeutic op.. 9/7 Details SourceReview
Review
IHU, Expert Review of Clinical Immunology (Review) (Peer Reviewed) (not included in the study count) Natural history and therapeutic options for COVID-19 Review of the current state of knowledge regarding the natural history of and therapeutic options for COVID-19. Treatment with an oral combination of hydroxychloroquine, azithromycin and zinc may represent the best current therapeutic option in relation to its antiviral and immunomodulatory effects. IHU et al., 9/7/2020, peer-reviewed, 1 author.Share Tweet
Submit Corrections or Comments9/5 Late
Synolaki et al., medRxiv, doi:10.1101/2020.09.05.20184655(Preprint)
death, ↓23.6%, p=0.27 The Activin/Follistatin-axis is severely deregulated in COVID-19 and independently associated with in-hospital mortality Details Retrospective 117 patients, 58 HCQ showing lower mortality for HCQ patients. Version 1 of this paper stated: "HCQ, AZ, were found to be independently associated with survival when treatment commenced at FACTCLINYCoD scores.. 9/5 Details SourceLate treatment study Late treatment study Synolaki et al., medRxiv, doi:10.1101/2020.09.05.20184655
(Preprint)
The Activin/Follistatin-axis is severely deregulated in COVID-19 and independently associated with in-hospital mortality Retrospective 117 patients, 58 HCQ showing lower mortality for HCQpatients.
Version 1 of this paper stated: "HCQ, AZ, were found to be independently associated with survival when treatment commenced at FACTCLINYCoD scores <3". risk of death, 23.6% lower, RR 0.76, _p_ = 0.27, treatment 21 of 98 (21.4%), control 60 of 214 (28.0%). Synolaki et al., 9/5/2020, retrospective, Greece, Europe, preprint,20 authors.
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Submit Corrections or Comments9/4 Late
Furtado et al., The Lancet, doi:10.1016/S0140-6736(20)31862-6(Peer Reviewed)
Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial Details Small RCT comparing the addition of AZ for very late stage patients on ventilation or oxygen. No significant difference was found, OR 1.36, _p_=0.11. One notable result is that even within this extremely late stage population, results sugge.. 9/4 Details SourceLate treatment study Late treatment study Furtado et al., The Lancet, doi:10.1016/S0140-6736(20)31862-6 (Peer
Reviewed)
Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial Small RCT comparing the addition of AZ for very late stage patients on ventilation or oxygen. No significant difference was found, OR 1.36, _p_=0.11. One notable result is that even within this extremely late stage population, results suggest increased efficacy with the addition of AZ for patients with earlier use of AZ/HCQ, OR 0.71,_p_=0.28.
Patients received 8g of HCQ over 10 days, approaching the high levels used in the RECOVERY trial (9.2g over 10 days), showing significantly more adverse events than typical trials. Since all patients were on HCQ, this study does not provide information on the efficacy of HCQ. Furtado et al., 9/4/2020, peer-reviewed, 33 authors.Share Tweet
Submit Corrections or Comments9/2 In Vitro
Wang et al., Phytomedicine, doi:10.1016/j.phymed.2020.153333 (Peer Reviewed) (In Vitro) (not included in the study count)_in vitro_
Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus Details _In Vitro_ study providing novel insights into the molecular mechanism of CQ/HCQ treatment, showing that CQ and HCQ both inhibit the entrance of 2019-nCoV into cells by blocking the binding of the virus with ACE2. 9/2 Details SourceIn Vitro
In Vitro
Wang et al., Phytomedicine, doi:10.1016/j.phymed.2020.153333 (Peer Reviewed) (In Vitro) (not included in the study count) Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus _In Vitro_ study providing novel insights into the molecular mechanism of CQ/HCQ treatment, showing that CQ and HCQ both inhibit the entrance of 2019-nCoV into cells by blocking the binding of thevirus with ACE2.
Wang et al., 9/2/2020, peer-reviewed, 34 authors.Share Tweet
Submit Corrections or Comments9/2 Early
Heras et al., European Geriatric Medicine, doi:10.1007/s41999-020-00432-w (preprint 9/2) (Peer Reviewed) death, ↓95.6%, p=0.004 COVID-19 mortality risk factors in older people in a long-term carecenter
Details Retrospective 100 elderly nursing home patients, HCQ+AZ mortality 11.4% vs. control 61.9%, RR 0.18, _p_<0.001. Median age 85. COVID-19 confirmed. 70% treated with HCQ+AZ. Details of differences between groups are not provided, and no adjus.. 9/2 Details SourceEarly treatment study Early treatment study Heras et al., European Geriatric Medicine, doi:10.1007/s41999-020-00432-w (preprint 9/2) (Peer Reviewed) COVID-19 mortality risk factors in older people in a long-term care
center
Retrospective 100 elderly nursing home patients, HCQ+AZ mortality 11.4% vs. control 61.9%, RR 0.18, _p_<0.001. Median age 85. COVID-19 confirmed. 70% treated with HCQ+AZ. Details of differences between groups are not provided, and no adjustments are made. It is not clear how the groups were selected. Authors indicate treatment was early but do not specify the treatment delay. risk of death, 95.6% lower, RR 0.04, _p_ = 0.004, treatment 8 of 70 (11.4%), control 16 of 30 (53.3%), adjusted. Heras et al., 9/2/2020, retrospective, Andorra, Europe, peer-reviewed, median age 85.0, 13 authors, dosage not specified.Share Tweet
Submit Corrections or Comments9/2 PrEP
de la Iglesia et al., medRxiv, doi:10.1101/2020.08.31.20185314(Preprint)
hosp., ↑50.0%, p=1.00 Hydroxicloroquine for pre-exposure prophyylaxis for SARS-CoV-2 Details Analysis of autoimmune disease patients on HCQ, compared to a control group from the general population (matched on age and sex, but not adjusted for autoimmune disease), showing non-significant differences between groups. Otherresearch..
9/2 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study de la Iglesia et al., medRxiv, doi:10.1101/2020.08.31.20185314
(Preprint)
Hydroxicloroquine for pre-exposure prophyylaxis for SARS-CoV-2 Analysis of autoimmune disease patients on HCQ, compared to a control group from the general population (matched on age and sex, but not adjusted for autoimmune disease), showing non-significant differencesbetween groups.
Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, _p_<0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more carefulto avoid exposure.
If we adjust for the different baseline risk, the mortality result becomes RR 0.35, _p_=0.23, suggesting a substantial benefit for HCQ treatment (as shown in other studies). c19study.com/ferri.html risk of hospitalization, 50.0% higher, RR 1.50, _p_ = 1.00, treatment 3 of 687 (0.4%), control 2 of 688 (0.3%). risk of COVID-19 case, 42.6% higher, RR 1.43, _p_ = 0.15, treatment 42 of 648 (6.5%), control 30 of 660 (4.5%), suspected COVID-19. risk of COVID-19 case, 7.8% lower, RR 0.92, _p_ = 0.84, treatment 12 of 678 (1.8%), control 13 of 677 (1.9%), confirmed COVID-19. de la Iglesia et al., 9/2/2020, retrospective, database analysis, Spain, Europe, preprint, 17 authors.Share Tweet
Submit Corrections or Comments9/1 Review
Hecel et al., Pharmaceuticals, 13:9, 228, doi:10.3390/ph13090228 (Review) (Peer Reviewed) (not included in the study count)review
Zinc(II)—The Overlooked Éminence Grise of Chloroquine’s Fightagainst COVID-19?
Details Review of zinc as an inhibitor of SARS-CoV-2′s RNA-dependent RNA polymerase, and zinc ionophores including CQ/HCQ, showing the latest evidence for zinc and CQ/HCQ having antiviral, and in particular anticoronaviral action. 9/1 Details SourceReview
Review
Hecel et al., Pharmaceuticals, 13:9, 228, doi:10.3390/ph13090228 (Review) (Peer Reviewed) (not included in the study count) Zinc(II)—The Overlooked Éminence Grise of Chloroquine’s Fightagainst COVID-19?
Review of zinc as an inhibitor of SARS-CoV-2′s RNA-dependent RNA polymerase, and zinc ionophores including CQ/HCQ, showing the latest evidence for zinc and CQ/HCQ having antiviral, and in particular anticoronaviral action. Hecel et al., 9/1/2020, peer-reviewed, 11 authors.Share Tweet
Submit Corrections or Comments9/1 Early
Elbazidi et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100749 (Peer Reviewed) Pandemic and social changes, political fate Details Analysis of US states and countries. Country analysis shows a significant correlation between the dates of decisions to adopt/decline HCQ, and corresponding trend changes in CFR. US state analysis shows a significant correlation between C.. 9/1 Details SourceEarly treatment study Early treatment study Elbazidi et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100749 (Peer Reviewed) Pandemic and social changes, political fate Analysis of US states and countries. Country analysis shows a significant correlation between the dates of decisions to adopt/decline HCQ, and corresponding trend changes in CFR. US state analysis shows a significant correlation between CFR and the level of
acceptance of HCQ.
Elbazidi et al., 9/1/2020, peer-reviewed, 2 authors.Share Tweet
Submit Corrections or Comments8/30 Late
Albani et al., J, Clinical Medicine, doi:10.3390/jcm9092800 (PeerReviewed)
death, ↓18.4%, p=0.05 Impact of Azithromycin and/or Hydroxychloroquine on Hospital Mortality in COVID-19 Details Retrospective 1376 hospitalized patients in Italy, 211 treated with HCQ and 166 with HCQ+AZ. 8/30 Details SourceLate treatment study Late treatment study Albani et al., J, Clinical Medicine, doi:10.3390/jcm9092800 (Peer
Reviewed)
Impact of Azithromycin and/or Hydroxychloroquine on Hospital Mortality in COVID-19 Retrospective 1376 hospitalized patients in Italy, 211 treated with HCQ and 166 with HCQ+AZ. risk of death, 18.4% lower, RR 0.82, _p_ = 0.05, treatment 60 of 211 (28.4%), control 172 of 605 (28.4%), adjusted, OR converted to RR, HCQvs. neither.
risk of death, 9.0% higher, RR 1.09, _p_ = 0.38, treatment 60 of 211 (28.4%), control 172 of 605 (28.4%), adjusted, OR converted to RR,HCQ+AZ vs. neither.
risk of ICU admission, 9.2% higher, RR 1.09, _p_ = 0.68, treatment 73 of 211 (34.6%), control 46 of 605 (7.6%), adjusted, OR converted to RR, HCQ vs. neither. risk of ICU admission, 71.3% higher, RR 1.71, _p_ < 0.001, treatment 73 of 211 (34.6%), control 46 of 605 (7.6%), adjusted, OR converted to RR, HCQ+AZ vs. neither. Albani et al., 8/30/2020, retrospective, Italy, Europe, peer-reviewed, 11 authors.Share Tweet
Submit Corrections or Comments8/29 Late
Castillo et al., Journal of Steroid Biochemistry and Molecular Biology, 203, October 2020, doi:10.1016/j.jsbmb.2020.105751 (PeerReviewed)
Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinicalstudy
Details RCT on calcifediol (25-hydroxyvitamin D) treatment for hospitalized COVID-19 patients showing significantly reduced intensive care unit admissions. All patients received standard care including HCQ+AZ. Significantly lower ICU admission wi.. 8/29 Details SourceLate treatment study Late treatment study Castillo et al., Journal of Steroid Biochemistry and Molecular Biology, 203, October 2020, doi:10.1016/j.jsbmb.2020.105751 (Peer
Reviewed)
Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinicalstudy
RCT on calcifediol (25-hydroxyvitamin D) treatment for hospitalized COVID-19 patients showing significantly reduced intensive care unit admissions. All patients received standard care including HCQ+AZ. Significantly lower ICU admission with the addition of calcifediol - adjusted odds ratio 0.03 . No deaths for calcifediol (0/50), 2 deaths for SOC (2/26). Castillo et al., 8/29/2020, peer-reviewed, 7 authors.Share Tweet
Submit Corrections or Comments8/28 Late
Fried et al., Clinical Infectious Disease, doi:10.1093/cid/ciaa1268 (Peer Reviewed) death, ↑27.0%, p<0.001 Patient Characteristics and Outcomes of 11,721 Patients with COVID19 Hospitalized Across the United States Details Database analysis of 11,721 hospitalized patients, 4,232 on HCQ. Strong evidence for confounding by indication and compassionate use of HCQ. 24.9% of HCQ patients were on mechanical ventilation versus 12.2% control. Ventilation mortality .. 8/28 Details SourceLate treatment study Late treatment study Fried et al., Clinical Infectious Disease, doi:10.1093/cid/ciaa1268
(Peer Reviewed)
Patient Characteristics and Outcomes of 11,721 Patients with COVID19 Hospitalized Across the United States Database analysis of 11,721 hospitalized patients, 4,232 on HCQ. Strong evidence for confounding by indication and compassionate use of HCQ. 24.9% of HCQ patients were on mechanical ventilation versus 12.2% control. Ventilation mortality was 70.5% versus 11.6%. This study does not adjust for the differences in comorbid conditions and disease severity, and therefore does not make a conclusion. Unadjusted HCQ mortality was 24.8% versus control 19.6%. Adjusting for ventilation only gives us 17.7% HCQ versus 19.6% control (adjusting the HCQ group to have the same proportion of ventilation patients), RR 0.90. Hopefully authors can do a full adjustment analysis. Comorbidities may favor control, while patients remaining in the hospital (5.3%) may favor HCQ (other studies show faster resolutionfor HCQ patients).
Data inconsistencies have been found in this study, for example 99.4% of patients treated with HCQ were treated in urban hospitals, compared to 65% of untreated patients (Supplemental Table 3), while patients are distributed in a more balanced manner between teaching or not-teaching hospitals, as well as in the most urbanized (Northeast) and less urbanized (Midwest) regions of the United States . academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1618/5934822 risk of death, 27.0% higher, RR 1.27, _p_ < 0.001, treatment 1048 of 4232 (24.8%), control 1466 of 7489 (19.6%). Fried et al., 8/28/2020, retrospective, database analysis, USA, North America, peer-reviewed, 11 authors.Share Tweet
Submit Corrections or Comments8/27 PrEP
Ferri at al., Clinical Rheumatology, doi:0.1007/s10067-020-05334-7(Peer Reviewed)
cases, ↓63.0%, p=0.01 COVID-19 and rheumatic autoimmune systemic diseases: report of a large Italian patients series Details Analysis of 1641 systemic autoimmune disease patients showing csDMARD (HCQ etc.) RR 0.37, _p_=0.015. csDMARDs include HCQ, CQ, and several other drugs, so the effect of HCQ/CQ alone could be higher. This study also confirms that the risk..
8/27 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Ferri at al., Clinical Rheumatology, doi:0.1007/s10067-020-05334-7
(Peer Reviewed)
COVID-19 and rheumatic autoimmune systemic diseases: report of a large Italian patients series Analysis of 1641 systemic autoimmune disease patients showing csDMARD (HCQ etc.) RR 0.37, _p_=0.015. csDMARDs include HCQ, CQ, and several other drugs, so the effect of HCQ/CQ alone could be higher. This study also confirms that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, OR 4.42, _p_<0.001 (this is the observed real-world risk which takes into account factors such as these patients potentially being more careful to avoidexposure).
(results are for "definite + highly suspected" cases and the main result is presented in the paper as the OR for not taking csDMARDs, we have converted this to RR for taking csDMARDs). risk of COVID-19 case, 63.0% lower, RR 0.37, _p_ = 0.01, treatment 9 of 994 (0.9%), control 16 of 647 (2.5%). Ferri et al., 8/27/2020, retrospective, Italy, Europe, peer-reviewed,survey, 29 authors.
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Submit Corrections or Comments8/26 Late
Fiolet et al., Clinical Microbiology and Infection (Peer Reviewed) (meta analysis - not included in study count)meta-analysis
Effect of hydroxychloroquine with or without azithromycin on the mortality of COVID-19 patients: a systematic review and meta-analysis Details Meta analysis of late stage studies (and one early treatment study with only 2 deaths), showing HCQ RR 0.83 , before exclusions RR 0.80 . Authors claim "HCQ alone is not effective", but the result directly .. 8/26 Details SourceLate treatment study Late treatment study Fiolet et al., Clinical Microbiology and Infection (Peer Reviewed) (meta analysis - not included in study count) Effect of hydroxychloroquine with or without azithromycin on the mortality of COVID-19 patients: a systematic review and meta-analysis Meta analysis of late stage studies (and one early treatment study with only 2 deaths), showing HCQ RR 0.83 , before exclusions RR 0.80 . Authors claim "HCQ alone is not effective", but the result directly contradicts this, RR 0.83 , i.e., inconclusive but much more likely to be effective than not. There are many errors in this meta analysis which introduce critical
bias, for example:
- Very biased sample of studies, including <4% of early treatment studies (only 1), and <30% of late treatment studies, focused onnegative studies.
- Arshad et al. (propensity matched HR 0.49, _p_=0.009) was excluded because the authors claim a "critical" risk of confounding bias due to steroid use, however steroids were controlled for in the multivariate and propensity analyses . - For Skipper et al., authors use an RR of 1.01, however the study had one hospitalized control death and one non-hospitalized HCQ death. Since the HCQ death was non-hospitalized, it may not be caused by COVID-19, or the patient did not receive standard care, therefore this should not be treated as equal to the control death. Further, medication adherence was only 77%, the HCQ patient may not have taken the medication (Skipper et al. neglects to answer this question). In any case, including a trial with only 1-2 deaths is likely to increasebias.
- Cavalcanti et al. received the lowest bias rating, despite having treatment delayed up to 14 days after symptoms, randomizing 14% of patients in the ICU, having significant protocol deviations, unusually low medication adherence, randomization that resulted in 64.3% male patients (HCQ) vs. 54.2% (control), and excluding patients already receiving longer and potentially therapeutic doses of the studytreatments.
- Sbidian el al. received the lowest bias rating, however many more control patients are still in hospital at 28 days suggesting there will be a significant improvement when extending past 28 days. - The RECOVERY trial received the lowest bias rating, despite using a very high dose likely responsible for the increased mortality. Results of this trial are not relevant to use at normal dosages. - Inclusion criteria required RT-PCR confirmed cases, but this was disregarded when including Horby et al. (very negative, excessive dose) and Skipper et al. - Authors do not consider different treatment delays, risk level of patients, differences in dosage, or usage of Zinc. Also see many other reports of problems and fatal flaws: This analysis is also missing several recent studies, for a more up-to-date analysis see . ijidonline.com/article/S1201-9712(20)30604-4/fulltext clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30649-2/fulltext mediterranee-infection.com/wp-content/uploads/2020/04/Response-to-Fiolet-et-al-Manuscript.pdf francesoir.fr/societe-sante/covid-19-les-anti-hydroxychloroquine-et-une-certaine-science-francaise.. twitter.com/Covid19Crusher/status/1299746474478243841 twitter.com/Covid19Crusher/status/1321426322049142791 c19study.com/ihu.html Fiolet et al., 8/26/2020, peer-reviewed, 6 authors.Share Tweet
Submit Corrections or Comments8/25 Early
Ip et al., BMC Infectious Diseases, doi:10.1186/s12879-021-05773-w (preprint 8/25) (Peer Reviewed) death, ↓54.5%, p=0.43 Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: A multi-center observational study Details Retrospective 1,274 outpatients, 47% reduction in hospitalization with HCQ with propensity matching, HCQ OR 0.53 . Sensitivity analyses revealed similar associations. Adverse events were not increased (2% QTc prolongation even.. 8/25 Details SourceEarly treatment study Early treatment study Ip et al., BMC Infectious Diseases, doi:10.1186/s12879-021-05773-w (preprint 8/25) (Peer Reviewed) Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: A multi-center observational study Retrospective 1,274 outpatients, 47% reduction in hospitalization with HCQ with propensity matching, HCQ OR 0.53 . Sensitivity analyses revealed similar associations. Adverse events were not increased (2% QTc prolongation events, 0%
arrhythmias).
risk of death, 54.5% lower, RR 0.45, _p_ = 0.43, treatment 2 of 97 (2.1%), control 44 of 970 (4.5%). risk of ICU admission, 28.6% lower, RR 0.71, _p_ = 0.79, treatment 3 of 97 (3.1%), control 42 of 970 (4.3%). risk of hospitalization, 37.3% lower, RR 0.63, _p_ = 0.04, treatment 21 of 97 (21.6%), control 305 of 970 (31.4%), adjusted, OR convertedto RR.
Ip et al., 8/25/2020, retrospective, database analysis, USA, North America, peer-reviewed, 25 authors, dosage not specified.Share Tweet
Submit Corrections or Comments8/25 Late
Di Castelnuovo et al., European J. Internal Medicine, doi:10.1016/j.ejim.2020.08.019 (Peer Reviewed) death, ↓30.0%, p<0.0001 Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study Details Retrospective 3,451 hospitalized patients, 30% reduction in mortality with HCQ after propensity adjustment, HR 0.70 . 8/25 Details SourceLate treatment study Late treatment study Di Castelnuovo et al., European J. Internal Medicine, doi:10.1016/j.ejim.2020.08.019 (Peer Reviewed) Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study Retrospective 3,451 hospitalized patients, 30% reduction in mortality with HCQ after propensity adjustment, HR 0.70 . risk of death, 30.0% lower, RR 0.70, _p_ < 0.001, treatment 386 of 2634 (14.7%), control 90 of 817 (11.0%), adjusted. Di Castelnuovo et al., 8/25/2020, retrospective, Italy, Europe, peer-reviewed, 110 authors.
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Submit Corrections or Comments8/24 Late
Catteau et al., Int. J. Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106144 (Peer Reviewed) death, ↓32.0%, p<0.0001 Low-dose Hydroxychloroquine Therapy and Mortality in Hospitalized Patients with COVID-19: A Nationwide Observational Study of 8075Participants
Details Retrospective 8,075 hospitalized patients, 4,542 low-dose HCQ, 3,533 control. 35% lower mortality for HCQ (17.7% vs. 27.1%), adjusted HR 0.68 . Low-dose HCQ monotherapy was independently associated with lower mortality inhospi..
8/24 Details SourceLate treatment study Late treatment study Catteau et al., Int. J. Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106144 (Peer Reviewed) Low-dose Hydroxychloroquine Therapy and Mortality in Hospitalized Patients with COVID-19: A Nationwide Observational Study of 8075
Participants
Retrospective 8,075 hospitalized patients, 4,542 low-dose HCQ, 3,533 control. 35% lower mortality for HCQ (17.7% vs. 27.1%), adjusted HR 0.68 . Low-dose HCQ monotherapy was independently associated with lower mortality in hospitalized patients. Patients exposed to others therapies (TCZ, AZ, LPV/RTV) were excluded. Statistical analysis was performed by an independent group. Calendar time of prescription and immortal time bias was taken into account. Corticosteroids prescriptions was low in both groups. risk of death, 32.0% lower, RR 0.68, _p_ < 0.001, treatment 804 of 4542 (17.7%), control 957 of 3533 (27.1%). Catteau et al., 8/24/2020, retrospective, database analysis, Belgium, Europe, peer-reviewed, 11 authors.Share Tweet
Submit Corrections or Comments8/23 Late
Pasquini et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkaa321 (Peer Reviewed) death, ↓16.4%, p=0.34 Effectiveness of remdesivir in patients with COVID-19 under mechanical ventilation in an Italian ICU Details Retrospective 51 ICU patients under mechanical ventilation, 33 treated with HCQ, showing unadjusted lower mortality with treatment. 8/23 Details SourceLate treatment study Late treatment study Pasquini et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkaa321 (Peer Reviewed) Effectiveness of remdesivir in patients with COVID-19 under mechanical ventilation in an Italian ICU Retrospective 51 ICU patients under mechanical ventilation, 33 treated with HCQ, showing unadjusted lower mortality with treatment. risk of death, 16.4% lower, RR 0.84, _p_ = 0.34, treatment 23 of 33 (69.7%), control 15 of 18 (83.3%). Pasquini et al., 8/23/2020, retrospective, Italy, Europe, peer-reviewed, 9 authors.
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Submit Corrections or Comments8/21 Early
Ly et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106219 (preprint 8/21) (Peer Reviewed) death, ↓55.6%, p=0.02 Pattern of SARS-CoV-2 infection among dependant elderly residents living in retirement homes in Marseille, France, March-June 2020 Details Retrospective analysis of retirement homes, HCQ+AZ >= 3 days mortality OR 0.37, _p_=0.02. 1690 elderly residents (mean age 83), 226 infected residents, 116 treated with HCQ+AZ >= 3 days. Detection via mass screening also showed significant.. 8/21 Details SourceEarly treatment study Early treatment study Ly et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106219 (preprint 8/21) (Peer Reviewed) Pattern of SARS-CoV-2 infection among dependant elderly residents living in retirement homes in Marseille, France, March-June 2020 Retrospective analysis of retirement homes, HCQ+AZ >= 3 days mortality OR 0.37, _p_=0.02. 1690 elderly residents (mean age 83), 226 infected residents, 116 treated with HCQ+AZ >= 3 days. Detection via mass screening also showed significant improvements (16.9% vs. 40.6%, OR 0.20, _p_=0.001), suggesting that earlier detection and treatment is more successful. risk of death, 55.6% lower, RR 0.44, _p_ = 0.02, treatment 18 of 116 (15.5%), control 29 of 110 (26.4%), adjusted, OR converted to RR. Ly et al., 8/21/2020, retrospective, France, Europe, peer-reviewed, mean age 83.0, 21 authors, dosage 200mg tid days 1-10.
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Submit Corrections or Comments8/21 N/A
Lane et al., The Lancet Rheumatology, doi:10.1016/S2665-9913(20)30276-9 (Peer Reviewed) (not included in thestudy count)
safety analysis
Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study Details Retrospective study of RA patients using HCQ vs. sulfasalazine (another DMARD). HCQ treatment showed no increased risk in the short term (up to 30 days) among patients with RA. Long term use was associated with excess cardiovascular morta.. 8/21 Details SourceN/A
N/A
Lane et al., The Lancet Rheumatology, doi:10.1016/S2665-9913(20)30276-9 (Peer Reviewed) (not included in thestudy count)
Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study Retrospective study of RA patients using HCQ vs. sulfasalazine (another DMARD). HCQ treatment showed no increased risk in the short term (up to 30 days) among patients with RA. Long term use was associated with excess cardiovascular mortality. Addition of AZ increased the risk of cardiovascular mortality with combined use up to 30 days. This is several times longer than typical COVID-19 use. This result also comes from just 2 of the 14 databases, with the negative result from just one database (VA) and much lower statistically insignifant difference in mortality from the other database (Clinformatics). Confounding by indication. Patients conditions vary, the severity of a patient's RA or other conditions was not taken into account. Results varied widely across different databases, and different subsets of databases were used in different analyses. Baseline risk of serious adverse events unknown. Health care database analysis subject to misclassification errors. Lane et al., 8/21/2020, peer-reviewed, 62 authors.Share Tweet
Submit Corrections or Comments8/21 Late
Gonzalez et al., medRxiv, doi:10.1101/2020.08.18.20172874(Preprint)
death, ↓26.6%, p=0.06 The Prognostic Value of Eosinophil Recovery in COVID-19: A Multicentre, Retrospective Cohort Study on Patients Hospitalised inSpanish Hospitals
Details Retrospective study focused on eosinophil recovery with 9,644 hospitalized patients in Spain, showing lower mortality for HCQ (14.7% vs 29.2%, _p_<0.001), and AZ (15.3% vs. 18.4%, _p_<0.001). With a multivariate model including potentialconf..
8/21 Details SourceLate treatment study Late treatment study Gonzalez et al., medRxiv, doi:10.1101/2020.08.18.20172874
(Preprint)
The Prognostic Value of Eosinophil Recovery in COVID-19: A Multicentre, Retrospective Cohort Study on Patients Hospitalised inSpanish Hospitals
Retrospective study focused on eosinophil recovery with 9,644 hospitalized patients in Spain, showing lower mortality for HCQ (14.7% vs 29.2%, _p_<0.001), and AZ (15.3% vs. 18.4%, _p_<0.001). With a multivariate model including potential confounding factors, HCQ and AZ are associated with lower mortality, HCQ OR 0.662, _p_=0.057. risk of death, 26.6% lower, RR 0.73, _p_ = 0.06, treatment 1246 of 8476 (14.7%), control 341 of 1168 (29.2%), adjusted, OR converted toRR.
Gonzalez et al., 8/21/2020, retrospective, database analysis, Spain, Europe, preprint, 25 authors.Share Tweet
Submit Corrections or Comments8/20 Late
Dubernet et al., J. Global Antimicrobial Resistance, doi:10.1016/j.jgar.2020.08.001 (Peer Reviewed) ICU, ↓87.6%, p=0.008 A comprehensive strategy for the early treatment of COVID-19 with azithromycin/hydroxychloroquine and/or corticosteroids: results of a retrospective observational study in the French overseas department ofReunion Island
Details Retrospective analysis of 36 hospitalized patients showing HCQ/AZ associated with lower ICU admission, _p_=0.008. Median age 66, no mortality. Confounding by indication, however it was patients with hypoxemic pneumonia that weretreated wit..
8/20 Details SourceLate treatment study Late treatment study Dubernet et al., J. Global Antimicrobial Resistance, doi:10.1016/j.jgar.2020.08.001 (Peer Reviewed) A comprehensive strategy for the early treatment of COVID-19 with azithromycin/hydroxychloroquine and/or corticosteroids: results of a retrospective observational study in the French overseas department of
Reunion Island
Retrospective analysis of 36 hospitalized patients showing HCQ/AZ associated with lower ICU admission, _p_=0.008. Median age 66, no mortality. Confounding by indication, however it was patients with hypoxemic pneumonia that were treated with HCQ/AZ, patients were not treated with HCQ/AZ if they didn't need oxygen therapy. risk of ICU admission, 87.6% lower, RR 0.12, _p_ = 0.008, treatment 1 of 17 (5.9%), control 9 of 19 (47.4%). Dubernet et al., 8/20/2020, retrospective, France, Africa, peer-reviewed, median age 66.0, 20 authors.Share Tweet
Submit Corrections or Comments8/20 Early
Prodromos, C., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100747 (Peer Reviewed) (not included in thestudy count)
safety analysis
Hydroxychloroquine is protective to the heart, not harmful: Asystematic review
Details Review concluding that HCQ/AZ does not cause Torsade de Pointes or related deaths, HCQ decreases cardiac events, and HCQ should not be restricted in use for COVID-19 patients because of fear of cardiac mortality. 8/20 Details SourceEarly treatment study Early treatment study Prodromos, C., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100747 (Peer Reviewed) (not included in the
study count)
Hydroxychloroquine is protective to the heart, not harmful: Asystematic review
Review concluding that HCQ/AZ does not cause Torsade de Pointes or related deaths, HCQ decreases cardiac events, and HCQ should not be restricted in use for COVID-19 patients because of fear of cardiacmortality.
Prodromos et al., 8/20/2020, peer-reviewed, 3 authors.Share Tweet
Submit Corrections or Comments8/18 Late
Pinato et al., Cancer Discovery, doi:10.1158/2159-8290.CD-20-0773(Peer Reviewed)
death, ↓59.0%, p<0.0001 Clinical portrait of the SARS-CoV-2 epidemic in European cancerpatients
Details Restrospective 890 cancer patients with COVID-19, adjusted mortality HR for HCQ/CQ 0.41, _p_<0.0001. Confirmed SARS-CoV-2 infection was required, which may help focus on more severe cases. Analysis with Cox proportional hazard model. Poten.. 8/18 Details SourceLate treatment study Late treatment study Pinato et al., Cancer Discovery, doi:10.1158/2159-8290.CD-20-0773
(Peer Reviewed)
Clinical portrait of the SARS-CoV-2 epidemic in European cancerpatients
Restrospective 890 cancer patients with COVID-19, adjusted mortality HR for HCQ/CQ 0.41, _p_<0.0001. Confirmed SARS-CoV-2 infection was required, which may help focus on more severe cases. Analysis with Cox proportional hazard model. Potential unmeasured confounders. risk of death, 59.0% lower, RR 0.41, _p_ < 0.001, treatment 30 of 182 (16.5%), control 181 of 446 (40.6%). Pinato et al., 8/18/2020, retrospective, multiple countries, Europe, peer-reviewed, 64 authors.Share Tweet
Submit Corrections or Comments8/15 Late
Peters et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.10.004 (preprint 8/15) (Peer Reviewed) death, ↑9.0%, p=0.57 Outcomes of Persons With COVID-19 in Hospitals With and Without Standard Treatment With (Hydroxy)chloroquine Details Retrospective study of HCQ use in 9 hospitals in the Netherlands, showing no significant difference in mortality with HCQ/CQ or dexamethasone. Late stage (admitted to hospital with positive test or CT scan abnormalities). 4 of 7hospitals..
8/15 Details SourceLate treatment study Late treatment study Peters et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.10.004 (preprint 8/15) (Peer Reviewed) Outcomes of Persons With COVID-19 in Hospitals With and Without Standard Treatment With (Hydroxy)chloroquine Retrospective study of HCQ use in 9 hospitals in the Netherlands, showing no significant difference in mortality with HCQ/CQ or dexamethasone. Late stage (admitted to hospital with positive test or CT scan abnormalities). 4 of 7 hospitals started treatment only after further deterioration. Short cutoff (21 days) - other studies have shown treated patient cases resolved faster and more control patients remaining in hospital at this time. In the preprint, 58 of 341 control patients died. In the journal version, 53 of 353 control patients died. Significant differences between hospitals - HCQ hospitals had significantly older patients with significantly more comorbidities. Non-HCQ hospitals were "tertiary academic centres" whereas HCQ hospitals were "secondary care hospitals". Residual confounding likely. This study compares overcrowded regular hospitals with undercrowded academic hospitals. A subset of patients were excluded due to transfer to other hospitals. This introduces bias because patients in critical condition are not transferred. For examples, patients benefiting from HCQ treatment may have been transferred to the tertiary centres and excluded from analysis, increasing the percentage of critical cases in the secondary
hospitals.
Among the seven (H)CQ-hospitals, the timing of start of (H)CQ treatment differed; three hospitals started at the moment of COVID-19 diagnosis, four started after diagnosis but only when patients clinically deteriorated e.g., when there was an increase in respiratory rate or increase in use of supplemental oxygen. Most patients received CQ instead of the safer HCQ, receiving late treatment with CQ. Patients were given an initial dose of 600mg CQ then every 12 hours, for 5 days a dose of 300 mg, for a total of 3600mg CQ. This dose is likely to be toxic, see for example . Authors mention a subset of hospitals started treatment relatively earlier, which seems like the most important area to analyze, but no results are provided. apps.who.int/iris/bitstream/handle/10665/65773/WHO_MAL_79.906.pdf risk of death, 9.0% higher, RR 1.09, _p_ = 0.57, treatment 419 of 1596 (26.3%), control 53 of 353 (15.0%), adjusted. Peters et al., 8/15/2020, retrospective, Netherlands, Europe, peer-reviewed, 21 authors.Share Tweet
Submit Corrections or Comments8/14 Late
Abd-Elsalam et al., American Journal of Tropical Medicine and Hygiene, 10.4269/ajtmh.20-0873 (Peer Reviewed) death, ↑20.0%, p=1.00 Hydroxychloroquine in the Treatment of COVID-19: A Multicenter Randomized Controlled Study Details Small RCT in Egypt with 97/97 HCQ/control patients, showing 58% more recovery @28days for HCQ (53.6% HCQ, 34% control), _p_=0.009 (0.06 in the paper refers to the 5 combined recovery/death/ICU values). No significant difference inventilat..
8/14 Details SourceLate treatment study Late treatment study Abd-Elsalam et al., American Journal of Tropical Medicine and Hygiene, 10.4269/ajtmh.20-0873 (Peer Reviewed) Hydroxychloroquine in the Treatment of COVID-19: A Multicenter Randomized Controlled Study Small RCT in Egypt with 97/97 HCQ/control patients, showing 58% more recovery @28days for HCQ (53.6% HCQ, 34% control), _p_=0.009 (0.06 in the paper refers to the 5 combined recovery/death/ICU values). No significant difference in ventilation and mortality (<=6 examples in each case). Authors note the "sample size was not adequately powered for survival endpoint". Other studies have also shown treated patient cases resolved faster. Continuing analysis past 28 days would be useful. Group characteristics are given, with for example 36% vs. 26% smokers, but they do not identify which group is which. Group 1 and 2 have 97 patients but the total given is 175. risk of death, 20.0% higher, RR 1.20, _p_ = 1.00, treatment 6 of 97 (6.2%), control 5 of 97 (5.2%). risk of no recovery at day 28, 30.0% lower, RR 0.70, _p_ = 0.009, treatment 45 of 97 (46.4%), control 64 of 97 (66.0%). Abd-Elsalam et al., 8/14/2020, Randomized Controlled Trial, Egypt, Africa, peer-reviewed, 10 authors.
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Submit Corrections or Comments8/13 Late
Roomi et al., J. Medical Internet Research, doi:10.2196/21758(Peer Reviewed)
death, ↑37.7%, p=0.54 Efficacy of hydroxychloroquine and tocilizumab in patients with COVID-19: A single-center retrospective chart review Details Retrospective 176 hospitalized patients (144 HCQ, 32 control) showing no significant differences with HCQ or TCZ. Confounding by indication. 8/13 Details SourceLate treatment study Late treatment study Roomi et al., J. Medical Internet Research, doi:10.2196/21758 (Peer
Reviewed)
Efficacy of hydroxychloroquine and tocilizumab in patients with COVID-19: A single-center retrospective chart review Retrospective 176 hospitalized patients (144 HCQ, 32 control) showing no significant differences with HCQ or TCZ. Confounding by indication. risk of death, 37.7% higher, RR 1.38, _p_ = 0.54, treatment 13 of 144 (9.0%), control 6 of 32 (18.8%), adjusted, OR converted to RR. Roomi et al., 8/13/2020, retrospective, USA, North America, peer-reviewed, 11 authors.Share Tweet
Submit Corrections or Comments8/11 In Silico
Tarek et al., European Journal of Drug Metabolism and Pharmacokinetics, doi:10.1007/s13318-020-00640-6 (Peer Reviewed) Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy and Prevention Details _In Silico_ analysis of HCQ treatment showing concluding that HCQ may affect viral clearance if administered early enough when the virus is still confined to the pharyngeal cavity; HCQ's effects against SARS-CoV-2 might be exerted more thro.. 8/11 Details SourceIn Silico
In Silico
Tarek et al., European Journal of Drug Metabolism and Pharmacokinetics, doi:10.1007/s13318-020-00640-6 (Peer Reviewed) Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy and Prevention _In Silico_ analysis of HCQ treatment showing concluding that HCQ may affect viral clearance if administered early enough when the virus is still confined to the pharyngeal cavity; HCQ's effects against SARS-CoV-2 might be exerted more through enhanced cell-mediated immunity than direct antiviral effects; and the effects of HCQ on SARS-CoV-2 viral load may be missed in clinical trials if measurements are not done at the peak of viral replication; and the effects are only evident at dosages able to guarantee a certain plasma drug concentration, i.e., > 400 mg/day. Tarek et al., 8/11/2020, peer-reviewed, 2 authors.Share Tweet
Submit Corrections or Comments8/11 Early
Bakhshaliyev et al., J. Electrocardiology, doi:10.1016/j.jelectrocard.2020.08.008 (Peer Reviewed) (not includedin the study count)
safety analysis
The effect of 5-day course of hydroxychloroquine and azithromycin combination on QT interval in non-ICU COVID19(+) patient Details Safety study of 109 patients showing 5 days of HCQ+AZ did not lead to clinically significant QT prolongation or other conduction delays compared to baseline ECG innon-ICU patients.
8/11 Details SourceEarly treatment study Early treatment study Bakhshaliyev et al., J. Electrocardiology, doi:10.1016/j.jelectrocard.2020.08.008 (Peer Reviewed) (not included
in the study count)
The effect of 5-day course of hydroxychloroquine and azithromycin combination on QT interval in non-ICU COVID19(+) patient Safety study of 109 patients showing 5 days of HCQ+AZ did not lead to clinically significant QT prolongation or other conduction delays compared to baseline ECG in non-ICU patients. Bakhshaliyev et al., 8/11/2020, peer-reviewed, 5 authors.Share Tweet
Submit Corrections or Comments8/11 Late
Saleemi et al., medRxiv, doi:10.1101/2020.08.05.20151027(Preprint)
viral- time, ↑21.0%, p<0.05 Time to negative PCR from symptom onset in COVID-19 patients on Hydroxychloroquine and Azithromycin - A real world experience Details Retrospective 65 HCQ+AZ, 20 control patients, showing median time to negative PCR of 23 days for HCQ+AZ vs. 19 days for control. Confounding by indication. 100% of non-HCQ group had mild disease vs. 63% of the HCQ+AZ group. More comorbidi.. 8/11 Details SourceLate treatment study Late treatment study Saleemi et al., medRxiv, doi:10.1101/2020.08.05.20151027 (Preprint) Time to negative PCR from symptom onset in COVID-19 patients on Hydroxychloroquine and Azithromycin - A real world experience Retrospective 65 HCQ+AZ, 20 control patients, showing median time to negative PCR of 23 days for HCQ+AZ vs. 19 days for control. Confounding by indication. 100% of non-HCQ group had mild disease vs. 63% of the HCQ+AZ group. More comorbidities and symptoms in the HCQ+AZ
group.
median time to PCR-, 21.0% higher, relative time 1.21, _p_ < 0.05, treatment 65, control 20. Saleemi et al., 8/11/2020, retrospective, Saudi Arabia, Middle East, preprint, 5 authors.Share Tweet
Submit Corrections or Comments8/8 Late
Lopez et al., Int. J. Antimicrob. Agents, doi:/j.ijantimicag.2020.106136 (Peer Reviewed) Effects of Hydroxychloroquine on Covid-19 in Intensive Care Unit Patients: Preliminary Results Details Small retrospective study of 29 ICU patients comparing those with HCQ plasma concentration within target to those with a concentration below the target value, with no significant differences found. Mortality in the on-target group was 0%..
8/8 Details SourceLate treatment study Late treatment study Lopez et al., Int. J. Antimicrob. Agents, doi:/j.ijantimicag.2020.106136 (Peer Reviewed) Effects of Hydroxychloroquine on Covid-19 in Intensive Care Unit Patients: Preliminary Results Small retrospective study of 29 ICU patients comparing those with HCQ plasma concentration within target to those with a concentration below the target value, with no significant differences found. Mortality in the on-target group was 0% versus 17% for the off-target group, mortality relative risk 0.14, _p_ = 0.16. Lopez et al., 8/8/2020, peer-reviewed, 8 authors.
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Submit Corrections or Comments8/6 PrEP
Salvarani et al., Arthritis & Rheumatology, doi:10.1002/art.41475(Peer Reviewed)
cases, ↓6.0%, p=0.75 Susceptibility to COVID‐19 in Patients Treated With Antimalarials: A Population‐Based Study in Emilia‐Romagna,Northern Italy
Details Comparison of CQ/HCQ users with the general population in a region of Italy, showing no significant difference in the probability of COVID-19. CQ/HCQ users were mostly systemic autoimmune disease patients and authors do not adjust forth..
8/6 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Salvarani et al., Arthritis & Rheumatology, doi:10.1002/art.41475
(Peer Reviewed)
Susceptibility to COVID‐19 in Patients Treated With Antimalarials: A Population‐Based Study in Emilia‐Romagna,Northern Italy
Comparison of CQ/HCQ users with the general population in a region of Italy, showing no significant difference in the probability ofCOVID-19.
CQ/HCQ users were mostly systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, _p_<0.001 . c19study.com/ferri.html risk of COVID-19 case, 6.0% lower, RR 0.94, _p_ = 0.75. Salvarani et al., 8/6/2020, retrospective, population-based cohort, Italy, Europe, peer-reviewed, 18 authors.Share Tweet
Submit Corrections or Comments8/6 Review
McCullough et al., The American Journal of Medicine, doi:10.1016/j.amjmed.2020.07.003 (Review) (Peer Reviewed) (not included in the study count)review
Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection Details Review of pathophysiological principles related to early outpatient treatment and therapeutic approaches including reduction of reinoculation, combination antiviral therapy, immunomodulation, antiplatelet/antithrombotic therapy, andadmin..
8/6 Details SourceReview
Review
McCullough et al., The American Journal of Medicine, doi:10.1016/j.amjmed.2020.07.003 (Review) (Peer Reviewed) (not included in the study count) Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection Review of pathophysiological principles related to early outpatient treatment and therapeutic approaches including reduction of reinoculation, combination antiviral therapy, immunomodulation, antiplatelet/antithrombotic therapy, and administration of oxygen, monitoring, and telemedicine. Proposes an algorithm based on age and comorbidities that allows for a large proportion to be monitored and treated at home during self-isolation with the aim of reducing the risks of hospitalizationand death.
McCullough et al., 8/6/2020, peer-reviewed, 23 authors.Share Tweet
Submit Corrections or Comments 8/6 PEP, Early, Late Watanabe et al., Open Letter (Letter) (meta analysis - not included in study count)meta-analysis
Concerns regarding the misinterpretation of statistical hypothesis testing in clinical trials for COVID-19 Details Open letter signed by 38 professors and doctors regarding misinterpretation of statistics in HCQ RCTs. Authors note that data from RCTs for early treatment in outpatients to date actually show favorable effects, especially inhigh-ri..
8/6 Details SourcePEP, Early, Late
PEP, Early, Late
Watanabe et al., Open Letter (Letter) (meta analysis - not includedin study count)
Concerns regarding the misinterpretation of statistical hypothesis testing in clinical trials for COVID-19 Open letter signed by 38 professors and doctors regarding misinterpretation of statistics in HCQ RCTs. Authors note that data from RCTs for early treatment in outpatients to date actually show favorable effects, especially in high-risk patients such as the elderly, where efficacy was up to three times higher than in young people. Because most samples were made up of young people without comorbidities, the studies were statistically inconclusive with the entire samples. Authors note that instead of the papers reporting this, they incorrectly claim that the treatment had no effect compared to the placebo. “This misinterpretation in statistical tests is well known and explained in most undergraduate books in the field,” says Watanabe. "An article published in Nature last year states that about 51% of the work on clinical trials with this type of result has incorrect conclusions." veja.abril.com.br/saude/especialistas-contestam-estudos-que-nao-viram-beneficios-na-cloroquina/amp/ Watanabe et al., 8/6/2020, preprint, 42 authors.Share Tweet
Submit Corrections or Comments8/5 PrEP
Singer et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-218500 (Letter) cases, ↑9.0%, p=0.62 Hydroxychloroquine ineffective for COVID-19 prophylaxis in lupus and rheumatoid arthritis Details Comparison of the percentage of SLE/RA patients on immunosuppressants that were taking HCQ, for COVID-19 diagnosis versus other infections or outpatient visits, finding a similar percentage in each case. No mortality of severity informat.. 8/5 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Singer et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-218500 (Letter) Hydroxychloroquine ineffective for COVID-19 prophylaxis in lupus and rheumatoid arthritis Comparison of the percentage of SLE/RA patients on immunosuppressants that were taking HCQ, for COVID-19 diagnosis versus other infections or outpatient visits, finding a similar percentage in each case. No mortality of severity information is provided to determine if HCQ treated patients fared better. No adjustment for concomitant medications or severity. risk of COVID-19 case, 9.0% higher, RR 1.09, _p_ = 0.62, treatment 55 of 10700 (0.5%), control 104 of 22058 (0.5%). Singer et al., 8/5/2020, retrospective, database analysis, USA, North America, preprint, 3 authors.
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Kalligeros et al., Journal of Global Antimicrobial Resistance, doi:10.1016/j.jgar.2020.07.018 (Peer Reviewed) death, ↑67.0%, p=0.57 Hydroxychloroquine use in hospitalised patients with COVID-19: An observational matched cohort study Details Small retrospective database analysis of 36 patients receiving HCQ not showing significant differences. Confounding by indication is likely. 8/5 Details SourceLate treatment study Late treatment study Kalligeros et al., Journal of Global Antimicrobial Resistance, doi:10.1016/j.jgar.2020.07.018 (Peer Reviewed) Hydroxychloroquine use in hospitalised patients with COVID-19: An observational matched cohort study Small retrospective database analysis of 36 patients receiving HCQ not showing significant differences. Confounding by indication is
likely.
risk of death, 67.0% higher, RR 1.67, _p_ = 0.57, treatment 36,control 72.
Kalligeros et al., 8/5/2020, retrospective, USA, North America, peer-reviewed, 13 authors.Share Tweet
Submit Corrections or Comments8/4 Late
Kamran et al., medRxiv, doi:10.1101/2020.07.30.20165365 (Preprint) progression, ↓5.0%, p=1.00 Clearing the fog: Is HCQ effective in reducing COVID-19 progression: A randomized controlled trial Details Study of 349 low-risk hospitalized patients with 151 non-consenting or ineligible patients used as controls. SOC included zinc, vitamin C and vitamin D. A statistically significant improvement in PCR negativity is shown at day 7 with HCQ..
8/4 Details SourceLate treatment study Late treatment study Kamran et al., medRxiv, doi:10.1101/2020.07.30.20165365 (Preprint) Clearing the fog: Is HCQ effective in reducing COVID-19 progression: A randomized controlled trial Study of 349 low-risk hospitalized patients with 151 non-consenting or ineligible patients used as controls. SOC included zinc, vitamin C and vitamin D. A statistically significant improvement in PCR negativity is shown at day 7 with HCQ treatment, 52.1% (HCQ) versus 35.7% (control), _p_=0.001, but no statistically significant difference at day 14, or in progression. Patients were relatively young and there was no mortality. Only 3% of patients had any disease progression and all patients recovered, so there is little if any room for treatment benefit. Progression among higher-risk patients with comorbidities was lower with treatment (12.9% versus 28.6%, _p_=0.3,
very few cases).
Despite the title, this is not an RCT since patients self-selected the arm, or were chosen based on allergies/contraindications. The treatment group had about twice the number of patients with comorbidities. Treatment delay is unknown - it was recorded but not reported in the paper. Viral load was not measured. As with other studies, PCR may detect non-replicable viral nucleic acid, this is more likely at day 14. Details on the test accuracy are not provided, authors note that RT-PCR sensitivity ranges from 34-80%. risk of disease progression, 5.0% lower, RR 0.95, _p_ = 1.00, treatment 11 of 349 (3.2%), control 5 of 151 (3.3%). risk of disease progression, 54.8% lower, RR 0.45, _p_ = 0.30, treatment 4 of 31 (12.9%), control 2 of 7 (28.6%), with comorbidities. risk of viral+ at day 7, 25.5% lower, RR 0.74, _p_ = 0.001, treatment349, control 151.
risk of viral+ at day 14, 10.0% higher, RR 1.10, _p_ = 0.52, treatment 349, control 151. Kamran et al., 8/4/2020, prospective, Pakistan, South Asia, preprint,10 authors.
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Submit Corrections or Comments8/3 Late
Berenguer et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.07.024 (Peer Reviewed) death, ↓61.9%, p<0.0001 Characteristics and predictors of death among 4035 consecutively hospitalized patients with COVID-19 in Spain Details Retrospective 4035 hospitalized patients in Spain showing reduced mortality with HCQ (data is in the supplementary appendix). 8/3 Details SourceLate treatment study Late treatment study Berenguer et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.07.024 (Peer Reviewed) Characteristics and predictors of death among 4035 consecutively hospitalized patients with COVID-19 in Spain Retrospective 4035 hospitalized patients in Spain showing reduced mortality with HCQ (data is in the supplementary appendix). risk of death, 61.9% lower, RR 0.38, _p_ < 0.001, treatment 681 of 2618 (26.0%), control 939 of 1377 (68.2%). Berenguer et al., 8/3/2020, retrospective, Spain, Europe, peer-reviewed, 8 authors.
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Yu et al., Science China Life Sciences, 2020 Aug 3, doi:10.1007/s11427-020-1782-1 (Letter) progression, ↓82.5%, p=0.05 Beneficial effects exerted by hydroxychloroquine in treating COVID-19 patients via protecting multiple organs Details Retrospective 2,882 patients in China, median age 62, 278 receiving HCQ, median 10 days post hospitalization, showing that HCQ treatment can reduce systemic inflammation and inhibit the cytokine storm, thus protecting multiple organs from.. 8/3 Details SourceLate treatment study Late treatment study Yu et al., Science China Life Sciences, 2020 Aug 3, doi:10.1007/s11427-020-1782-1 (Letter) Beneficial effects exerted by hydroxychloroquine in treating COVID-19 patients via protecting multiple organs Retrospective 2,882 patients in China, median age 62, 278 receiving HCQ, median 10 days post hospitalization, showing that HCQ treatment can reduce systemic inflammation and inhibit the cytokine storm, thus protecting multiple organs from inflammatory injuries, such as detoxification in the liver and attenuation of cardiac injury. IL-6 levels significantly reduced after HCQ treatment, _p_<0.05, and elevated after HCQ withdrawal. The significantly lower dose used here is potentially related to the different observations from the RECOVERY trial results. Authors suggest that treatment should be started as
soon as possible.
The 550 patients that were critically ill at baseline are reported in a separate paper. For the non-critically-ill patients at baseline, the proportion of patients that became critically ill was significantly lower for those treated with HCQ. For the subset of patients that started HCQ treatment early only 1.4% died versus 3.9% for HCQ started late and 9.1% for control patients. risk of progression to critical, 82.5% lower, RR 0.17, _p_ = 0.05, treatment 1 of 231 (0.4%), control 32 of 1291 (2.5%), baseline critical cohort reported separately in Yu et al.. risk of death, 85.0% lower, RR 0.15, _p_ = 0.02, treatment 1 of 73 (1.4%), control 238 of 2604 (9.1%), HCQ treatment started early vs.non-HCQ.
Yu et al., 8/3/2020, retrospective, China, Asia, preprint, median age62.0, 6 authors.
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Submit Corrections or Comments8/2 Late
Davido et al., Int. J. Antimicrobial Agents, 2020, doi:10.1016/j.ijantimicag.2020.106129 (Peer Reviewed) int./hosp., ↓55.0%, p=0.04 Impact of medical care including anti-infective agents use on the prognosis of COVID-19 hospitalized patients over time Details Retrospective of 132 hospitalized patients. HCQ+AZ(52)/AZ(28) significantly reduced death/ICU, HR=0.45, _p_=0.04. Adjusted for Charlson Comorbidity Index (including age), obesity, O2, lymphocyte count, and treatments. Mean delay fromadmiss..
8/2 Details SourceLate treatment study Late treatment study Davido et al., Int. J. Antimicrobial Agents, 2020, doi:10.1016/j.ijantimicag.2020.106129 (Peer Reviewed) Impact of medical care including anti-infective agents use on the prognosis of COVID-19 hospitalized patients over time Retrospective of 132 hospitalized patients. HCQ+AZ(52)/AZ(28) significantly reduced death/ICU, HR=0.45, _p_=0.04. Adjusted for Charlson Comorbidity Index (including age), obesity, O2, lymphocyte count, and treatments. Mean delay from admission to treatment 0.7
days.
risk of combined intubation/hospitalization, 55.0% lower, RR 0.45, _p_ = 0.04, treatment 12 of 80 (15.0%), control 13 of 40 (32.5%). Davido et al., 8/2/2020, retrospective, France, Europe, peer-reviewed, 14 authors.Share Tweet
Submit Corrections or Comments8/2 In Vitro
Sheaff, R., bioRxiv, doi:10.1101/2020.08.02.232892 (Preprint) (In Vitro) (not included in the study count)_in vitro_
A New Model of SARS-CoV-2 Infection Based on (Hydroxy)ChloroquineActivity
Details _In vitro_ study presenting a new theory on SARS-CoV-2 infection and why HCQ/CQ provides benefits, which potentially explains the observed relationships with smoking, diabetes, obesity, age, and treatment delay, and confirms theimportance ..
8/2 Details SourceIn Vitro
In Vitro
Sheaff, R., bioRxiv, doi:10.1101/2020.08.02.232892 (Preprint) (In Vitro) (not included in the study count) A New Model of SARS-CoV-2 Infection Based on (Hydroxy)ChloroquineActivity
_In vitro_ study presenting a new theory on SARS-CoV-2 infection and why HCQ/CQ provides benefits, which potentially explains the observed relationships with smoking, diabetes, obesity, age, and treatment delay, and confirms the importance of accurate dosing. Metabolic analysis revealed HCQ/CQ inhibit oxidative phosphorylation in mitochondria (likely by sequestering protons needed to drive ATP synthase), inhibiting infection and/or slowing replication. Sheaff et al., 8/2/2020, preprint, 1 author.Share Tweet
Submit Corrections or Comments8/1 Early
Bernabeu-Wittel et al., J. Gerontol. A Biol. Sci. Med. Sci., doi:10.1093/gerona/glaa192 (Peer Reviewed) death, ↓59.0%, p=0.03 Effectiveness of a On-Site Medicalization Program for Nursing Homes with COVID-19 Outbreaks Details Retrospective 272 nursing home residents showing significantly improved survival after establishing a treatment program including HCQ with or without lopinavir/ritonavir and with the addition of adjuvant and antimicrobial treatments depen.. 8/1 Details SourceEarly treatment study Early treatment study Bernabeu-Wittel et al., J. Gerontol. A Biol. Sci. Med. Sci., doi:10.1093/gerona/glaa192 (Peer Reviewed) Effectiveness of a On-Site Medicalization Program for Nursing Homes with COVID-19 Outbreaks Retrospective 272 nursing home residents showing significantly improved survival after establishing a treatment program including HCQ with or without lopinavir/ritonavir and with the addition of adjuvant and antimicrobial treatments depending on circumstances. Dosage details are in the supplementary appendix. Mortality relative risk is
from .
c19study.com/alexander.html risk of death, 59.0% lower, RR 0.41, _p_ = 0.03, treatment 189,control 83.
Bernabeu-Wittel et al., 8/1/2020, retrospective, Spain, Europe, peer-reviewed, 13 authors, dosage 400mg bid day 1, 200mg bid days 2-7.Share Tweet
Submit Corrections or Comments7/31
Mazzitelli et al., Travel Medicine and Infectious Disease, 37, doi:10.1016/j.tmaid.2020.101826 (Letter) (not included in the studycount)
Apparent inefficacy of hydroxychloroquine combined with azithromycin on SARS-CoV-2 clearance in an incident cohort of geriatric patients with COVID-19 Details Report on HCQ+AZ use in 41 elderly high-risk patients. 29 of 30 patients with treatment >= 5 days survived. Only 10% were PCR negative after one week, however the Ct value is not specified. 7/31 Details SourceMazzitelli et al., Travel Medicine and Infectious Disease, 37, doi:10.1016/j.tmaid.2020.101826 (Letter) (not included in the study
count)
Apparent inefficacy of hydroxychloroquine combined with azithromycin on SARS-CoV-2 clearance in an incident cohort of geriatric patients with COVID-19 Report on HCQ+AZ use in 41 elderly high-risk patients. 29 of 30 patients with treatment >= 5 days survived. Only 10% were PCR negative after one week, however the Ct value is not specified. Mazzitelli et al., 7/31/2020, preprint, 8 authors.Share Tweet
Submit Corrections or Comments7/29 Late
D'Arminio Monforte et al., Int. J. Infectious Diseases, doi:10.1016/j.ijid.2020.07.056 (Letter) death, ↓34.0%, p=0.12 Effectiveness of Hydroxychloroquine in COVID-19 disease: A done anddusted situation?
Details HCQ+AZ adjusted death HR 0.44, _p_=0.009. Propensity scores include baseline COVID-19 disease severity, age, gender, number of comorbidities, cardio-vascular disease, duration of symptoms, date of admission, baseline plasma CRP.IPW censori..
7/29 Details SourceLate treatment study Late treatment study D'Arminio Monforte et al., Int. J. Infectious Diseases, doi:10.1016/j.ijid.2020.07.056 (Letter) Effectiveness of Hydroxychloroquine in COVID-19 disease: A done and
dusted situation?
HCQ+AZ adjusted death HR 0.44, _p_=0.009. Propensity scores include baseline COVID-19 disease severity, age, gender, number of comorbidities, cardio-vascular disease, duration of symptoms, date of admission, baseline plasma CRP. IPW censoring. Retrospective study of 539 COVID-19 hospitalized patients in Milan, with treatment a median of 1 day after admission. HCQ 197 patients, HCQ+AZ 94, control 92. Control group received various other treatments. Authors excluded people receiving other drugs which could have biased the effect of HCQ when used in combination. Residual confounding is possible (e.g., people with CVD were more frequent in control), however people in the control group were more likely to require mechanical ventilation. risk of death, 34.0% lower, RR 0.66, _p_ = 0.12, treatment 53 of 197 (26.9%), control 47 of 92 (51.1%), adjusted. HCQ+AZ, 56.0% lower, RR 0.44, _p_ = 0.009, treatment 22 of 94 (23.4%), control 47 of 92 (51.1%), adjusted. D'Arminio Monforte et al., 7/29/2020, retrospective, Italy, Europe, preprint, 5 authors.Share Tweet
Submit Corrections or Comments7/28 Late
BaŞaran et al., Turk. J. Med. Sci., doi:10.3906/sag-2006-173(Peer Reviewed)
Outcome of Non-Critical COVID-19 Patients with Early Hospitalization and Early Antiviral Treatment Outside the ICU Details Observational study of 174 hospitalized patients in Turkey, median age 45.4, 23 treated with HCQ, 113 with HCQ+AZ, and 32 with regimens including favipiravir. 75% reduction in the median time to clinical improvement for HCQ+AZ vs. FAV, RR.. 7/28 Details SourceLate treatment study Late treatment study BaŞaran et al., Turk. J. Med. Sci., doi:10.3906/sag-2006-173 (Peer
Reviewed)
Outcome of Non-Critical COVID-19 Patients with Early Hospitalization and Early Antiviral Treatment Outside the ICU Observational study of 174 hospitalized patients in Turkey, median age 45.4, 23 treated with HCQ, 113 with HCQ+AZ, and 32 with regimens including favipiravir. 75% reduction in the median time to clinical improvement for HCQ+AZ vs. FAV, RR 0.25, _p_<0.001. 83% reduction for HCQ. However, there was significant confounding by indication. There were no significant adverse events. BaŞaran et al., 7/28/2020, prospective, Turkey, West Asia, peer-reviewed, 18 authors.Share Tweet
Submit Corrections or Comments7/26 PEP
Mitjà et al., NEJM, doi:10.1056/NEJMoa2021801 (preprint 7/26)(Peer Reviewed)
death, ↓51.7%, p=0.27 A Cluster-Randomized Trial of Hydroxychloroquine as Prevention of Covid-19 Transmission and Disease Details Death rate reduced from 0.6% to 0.4%, RR 0.68, not statistically significant due to low incidence (8 control cases, 5 treatment cases). For positive symptomatic cases, a greater effect is seen for nursing home residents, RR=0.49 [0.21 - .. 7/26 Details SourcePost Exposure Prophylaxis study Post Exposure Prophylaxis study Mitjà et al., NEJM, doi:10.1056/NEJMoa2021801 (preprint 7/26)
(Peer Reviewed)
A Cluster-Randomized Trial of Hydroxychloroquine as Prevention of Covid-19 Transmission and Disease Death rate reduced from 0.6% to 0.4%, RR 0.68, not statistically significant due to low incidence (8 control cases, 5 treatment cases). For positive symptomatic cases, a greater effect is seen for nursing home residents, RR=0.49 , vs. overall 0.89, possibly because the exposure events are identified faster in this context, versus home exposure where testing of the source may be more delayed. The trial is too small for significance here. If the trend continued this result would be significant at _p_<0.05 after about 25% more patients were added. There are 2 groups in this study: PCR+ at baseline (n=314) and PCR- at baseline (n=2000), which should be separated as they are different populations (primary outcome rates 18.6% and 22.2% compared to 3.0% and 4.3%). PCR+ already have COVID-19, so PEP analysis should be for the 2,000 PCR-, showing symptomatic COVID-19 of 4.3% (control) and 3.0% (treatment), RR 0.7, _p_=0.154. The paper has different RR values here, stating that they are adjusted for contact-level variables. It is not clear how they are computed - the adjusted RR for the overall sample is 4% lower, for PCR+ it is 20% lower, but for PCR- it is 107% higher, even though PCR- represents 86%of the sample.
Hopefully, supplementary data will provide a breakdown on cases in this PCR- @baseline sample by number of days since exposure, and also provide relevant hospitalisation and death results. Enrollment was up to 7 days after exposure, median 4 days. Treatment delay is unclear. The exposure event timing is not detailed. It appears to be based on the date of a positive test for a contact, which is likely to be much later than the actual exposure time. 13.1% were already positive at baseline, which is consistent with the actual exposure time being significantly earlier. PCR testing has a very high false-negative rate in early stages (e.g., 100% on day 1, 67% on day 4, and 20% on day 8 ), hence it is likely that a much higher percentage were infected at an unknown time before enrollment. Medication administration is not detailed. Sensitivity and specificity of the tests is not provided. Given the delay identifying index cases, PCR test delay, and PCR false negative rate at early stages, the treatment delay in general was very long and could be over 2 weeks. The RR for non-PCR positive at baseline is 0.74. Including the PCR-positive at baseline patients reduced this to 0.89. This is also consistent with earlier treatment being more effective. The paper does not mention zinc. Zinc deficiency in Spain has been reported at 83% , this may significantly reduce effectiveness. HCQ is a zinc ionophore which increases cellular uptake, facilitating significant intracellular concentrations of zinc, and zinc is known to inhibit SARS-CoV RNA-dependent RNA polymerase activity, and is widely thought to be important for effectiveness with SARS-CoV-2 . This study focuses on the existence of symptoms or PCR-positive results, however severity of symptoms is more important. Research has shown HCQ concentrations can be much higher in the lung compared to plasma , which may help minimize the occurrence of severe cases anddeath.
There is a treatment-delay response relationship consistent with an effective treatment, however the authors only provide 3 ranges and do not break down the earliest treatment delay times. The definition of COVID-19 symptoms is very broad - just existence of a headache alone or muscle pain alone was considered COVID-19. There was an overall very low incidence of confirmed COVID-19 (138 cases across both arms). There were no serious adverse events that were adjudicated as being treatment related. Authors exclude those with symptoms in the previous two weeks, however, those with symptoms up to several months before may still test PCR-positive even though there may be no viable virus. There appears to be incorrect data. Table 2, secondary outcomes, control, hospital/vital records shows that 8 of 1042 is 9.7% (we get0.8%).
Nasopharyngeal viral load analysis issues include test unreliability and temporo-spatial differences in viral shedding . In summary, this study appears positive in the context of very delayed treatment and very small sample sizes, however we have classified it as inconclusive for now pending further analysis and feedback. Preliminary analysis. Supplementary Appendix is not currently available. Please submit any corrections or comments. Data from this study has been used to show that viral load is the primary factor in transmission: . acpjournals.org/doi/10.7326/M20-1495 mdpi.com/2072-6643/9/7/697 infezmed.it/index.php/article?Anno=2020&numero=2&ArticoloDaVisualizzare=Vol_28_2_2020_192 ncbi.nlm.nih.gov/pmc/articles/PMC7122276/ journal.chestnet.org/article/S0012-3692(20)31718-9/fulltext medrxiv.org/content/10.1101/2020.10.27.20220277v1 risk of death, 51.7% lower, RR 0.48, _p_ = 0.27, treatment 4 of 1196 (0.3%), control 9 of 1301 (0.7%), per supplemental appendix table S7, one treatment death was a patient that did not take any study medication, they have been moved to the control group. risk of hospitalization, 21.4% lower, RR 0.79, _p_ = 0.59, treatment 13 of 1196 (1.1%), control 18 of 1301 (1.4%), per supplemental appendix table S7, one treatment death was a patient that did not take any study medication, they have been moved to the control group. baseline pcr- risk of cases, 32.0% lower, RR 0.68, _p_ = 0.27, treatment 29 of 958 (3.0%), control 45 of 1042 (4.3%). Mitjà et al., 7/26/2020, Randomized Controlled Trial, Spain, Europe, peer-reviewed, 12 authors.Share Tweet
Submit Corrections or Comments7/24 PrEP
Khurana et al., medRxiv, doi:10.1101/2020.07.21.20159301(Preprint)
cases, ↓51.0%, p=0.02 Prevalence and clinical correlates of COVID-19 outbreak among healthcare workers in a tertiary level hospital Details Study of hospital health care workers showing HCQ prophylaxis reduces COVID-19 significantly, OR 0.30, _p_=0.02. 94 positive health care workers with a matched sample of 87 testing negative. Full course prophylaxis was important in this stu.. 7/24 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Khurana et al., medRxiv, doi:10.1101/2020.07.21.20159301 (Preprint) Prevalence and clinical correlates of COVID-19 outbreak among healthcare workers in a tertiary level hospital Study of hospital health care workers showing HCQ prophylaxis reduces COVID-19 significantly, OR 0.30, _p_=0.02. 94 positive health care workers with a matched sample of 87 testing negative. Full course prophylaxis was important in this study which used a low dose of 400mg/week HCQ (800mg for week 1), so it may take longer to reach therapeutic levels. Actual benefit of HCQ may be larger because severity of symptoms are not considered here but HCQ may also reduce
severity.
risk of COVID-19 case, 51.0% lower, RR 0.49, _p_ = 0.02, treatment 6 of 22 (27.3%), control 88 of 159 (55.3%), OR converted to RR. Khurana et al., 7/24/2020, retrospective, India, South Asia, preprint, survey, 5 authors.Share Tweet
Submit Corrections or Comments7/23 Late
Cavalcanti et al., NEJM, July 23, 2020, doi:10.1056/NEJMoa2019014(Peer Reviewed)
death, ↓16.0%, p=0.77 Hydroxychloroquine with or without Azithromycin in Mild-to-ModerateCovid-19
Details Late stage RCT of 667 hospitalized patients with up to 14 days of symptoms at enrollment and receiving up to 4 liters per minute supplemental oxygen, not finding a significant effect after 15 days. Authors note: "the trial cannot de.. 7/23 Details SourceLate treatment study Late treatment study Cavalcanti et al., NEJM, July 23, 2020, doi:10.1056/NEJMoa2019014
(Peer Reviewed)
Hydroxychloroquine with or without Azithromycin in Mild-to-ModerateCovid-19
Late stage RCT of 667 hospitalized patients with up to 14 days of symptoms at enrollment and receiving up to 4 liters per minute supplemental oxygen, not finding a significant effect after 15 days. Authors note: "the trial cannot definitively rule out either a substantial benefit of the trial drugs or a substantial harm", sample sizes are too small. The paper uses the terms mild and moderate, however all patients had serious enough disease to be hospitalized, and 14% were actually randomized in the ICU. The trial had significant protocol deviations and unusually low medication adherence. Randomization resulted in 64.3% male patients (HCQ) vs. 54.2% (control) which may significantly affect results due to the much higher risk for male patients. Authors note: "our aim was to exclude patients already receiving longer and potentially therapeutic doses of the study treatments" in explanation for why the study protocol was changed to exclude patients with previous use of the medications >24hrs. Analyzing these patients rather than excluding them may have revealed effectiveness with early use as shown in other studies. The trial initially required enrollment within 48 hours of admission and was changed to remove this requirement, this change is likely to reduce effectiveness because enrollment was moved later, compared to the time the disease became serious enough for hospitalization. TotalHCQ dosage 5.6g.
A correction for 17 errors has been published: nejm.org/doi/full/10.1056/NEJMx200021 risk of death, 16.0% lower, RR 0.84, _p_ = 0.77, treatment 8 of 331 (2.4%), control 5 of 173 (2.9%), HCQ+HCQ/AZ. risk of hospitalization, 28.0% higher, RR 1.28, _p_ = 0.30, treatment 331, control 173, HCQ+HCQ/AZ. Cavalcanti et al., 7/23/2020, Randomized Controlled Trial, Brazil, South America, peer-reviewed, baseline oxygen requirements 41.8%, 14authors.
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Submit Corrections or Comments7/22 In Vitro
Ou et al., PLOS Pathogens, doi:10.1371/journal.ppat.1009212 (preprint 7/22) (Peer Reviewed) (In Vitro)_in vitro_
Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2 Details _In Vitro_ analysis showing that HCQ efficiently blocks viral entry mediated by cathepsin L, but not by TMPRSS2, and that a combination of HCQ and a TMPRSS2 inhibitor prevents SARS-CoV-2 infection more potently than either drug alone. 7/22 Details SourceIn Vitro
In Vitro
Ou et al., PLOS Pathogens, doi:10.1371/journal.ppat.1009212 (preprint 7/22) (Peer Reviewed) (In Vitro) Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2 _In Vitro_ analysis showing that HCQ efficiently blocks viral entry mediated by cathepsin L, but not by TMPRSS2, and that a combination of HCQ and a TMPRSS2 inhibitor prevents SARS-CoV-2 infection more potently than either drug alone. Ou et al., 7/22/2020, peer-reviewed, 6 authors.Share Tweet
Submit Corrections or Comments7/22 In Vitro
Hoffmann et al., Nature, (2020), doi:10.1038/s41586-020-2575-3 (Peer Reviewed) (In Vitro) (not included in the study count)_in vitro_
Chloroquine does not inhibit infection of human lung cells withSARS-CoV-2
Details The title of this paper does not appear to match the results. Fig. 1b @100uM shows CQ results in a ~4.5 fold decrease (on a linear scale) in extracellular virus, _p_=0.05, after 24 hours (we do not see the supplementary data at this time so.. 7/22 Details SourceIn Vitro
In Vitro
Hoffmann et al., Nature, (2020), doi:10.1038/s41586-020-2575-3 (Peer Reviewed) (In Vitro) (not included in the study count) Chloroquine does not inhibit infection of human lung cells withSARS-CoV-2
The title of this paper does not appear to match the results. Fig. 1b @100uM shows CQ results in a ~4.5 fold decrease (on a linear scale) in extracellular virus, _p_=0.05, after 24 hours (we do not see the supplementary data at this time so this is estimated from the graph). This decrease may continue if examined over longer time periods. Fig. 1a shows a ~45-50% entry inhibition @100uM for HCQ/CQ (_p_=0.0005/0.0045), ~10-30% @10uM (_p_=0.13/0.99). Inhibition is significantly better with Vero cells. Note that the safe concentration in practice for different cells is not well known, Keyaerts et al. find CC50 of 261uM . _In vitro_ study of CQ and HCQ inhibition of SARS-CoV-2 into Vero (kidney), Vero-TMPRSS2, and Calu-3 (derived from human lung carcinoma)cells.
Authors reportedly used sodium pyruvate which may inhibit CQ fromentering cells .
Although there are several theories on how HCQ may help with COVID-19, authors do not consider the most common theory where HCQ functions as a zinc ionophore, facilitating significant intracellular concentrations of zinc. Zinc is known to inhibit SARS-CoV RNA-dependent RNA polymerase activity, and is widely thought to be important for effectiveness with SARS-CoV-2 . Calu-3 is one of many cell lines derived from human lung carcinomas . Calu-3 cells resemble serous gland cells. They do not express 15-lipoxygenase, an enzyme specifically localized to the surface epithelium, but they do express secretory component, secretory leukocyte protease inhibitor, lysozyme, and lactoferrin, all markers of serous gland cells. note that the absence of systemic inflammation, circulatory factors, and other paracrine systemic influences is a potential limitation of the isolated cell system. RT-PCR is used, we note that nucleic acid may persist even after the virus is no longer viable . It is unclear how the authors conclude "CQ does not block SARS-CoV-2 infection of Calu-3" cells, when the results show statistically significant inhibition at higher concentrations. Further, it is unclear how the authors go from these results in one specific type of pulmonary adenocarcinoma cells that resemble serous gland cells, _in vitro_, into the title of the paper which claims no inhibition in lung cells. Further, it is unclear how another leap is made to "will not be effective against COVID-19" given the multiple theories of HCQ/CQeffectiveness.
c19study.com/keyaerts.html twitter.com/JaclynHord/status/1302680394244947969 infezmed.it/index.php/article?Anno=2020&numero=2&ArticoloDaVisualizzare=Vol_28_2_2020_192 journals.physiology.org/doi/pdf/10.1152/ajplung.1994.266.5.L493 journals.physiology.org/doi/pdf/10.1152/ajplung.1994.266.5.L493 fda.gov/media/136472/download Hoffmann et al., 7/22/2020, peer-reviewed, 10 authors.Share Tweet
Submit Corrections or Comments7/22 Late
Rivera et al., Cancer Discovery, doi:10.1158/2159-8290.CD-20-0941(Peer Reviewed)
death, ↑2.4%, p=0.90 Utilization of COVID-19 Treatments and Clinical Outcomes among Patients with Cancer: A COVID-19 and Cancer Consortium (CCC19) CohortStudy
Details Retrospective cancer patients, showing adjusted OR 1.03 for HCQ. The study reports the number of HCQ+AZ patients but they do not provide results for HCQ+AZ (only HCQ + any other treatment). Significant confounding by indicatio.. 7/22 Details SourceLate treatment study Late treatment study Rivera et al., Cancer Discovery, doi:10.1158/2159-8290.CD-20-0941
(Peer Reviewed)
Utilization of COVID-19 Treatments and Clinical Outcomes among Patients with Cancer: A COVID-19 and Cancer Consortium (CCC19) CohortStudy
Retrospective cancer patients, showing adjusted OR 1.03 for HCQ. The study reports the number of HCQ+AZ patients but they do not provide results for HCQ+AZ (only HCQ + any other treatment). Significant confounding by indication and compassionate use is likely. risk of death, 2.4% higher, RR 1.02, _p_ = 0.90, treatment 44 of 179 (24.6%), control 59 of 327 (18.0%), adjusted, OR converted to RR. Rivera et al., 7/22/2020, retrospective, USA, North America, peer-reviewed, 45 authors.Share Tweet
Submit Corrections or Comments7/22 Late
Kelly et al., British Journal of Clinical Pharmacology, doi:10.1111/bcp.14482 (Peer Reviewed) death, ↑143.0%, p=0.03 Clinical outcomes and adverse events in patients hospitalised with COVID‐19, treated with off‐label hydroxychloroquine andazithromycin
Details Retrospective 82 hospitalized patients HCQ/AZ, 52 SOC, not finding statistically significant differences. Confounding by indication - authors note that the HCQ/AZ patients were more severely ill, and do not attempt to adjust for confounde.. 7/22 Details SourceLate treatment study Late treatment study Kelly et al., British Journal of Clinical Pharmacology, doi:10.1111/bcp.14482 (Peer Reviewed) Clinical outcomes and adverse events in patients hospitalised with COVID‐19, treated with off‐label hydroxychloroquine and
azithromycin
Retrospective 82 hospitalized patients HCQ/AZ, 52 SOC, not finding statistically significant differences. Confounding by indication - authors note that the HCQ/AZ patients were more severely ill, and do not attempt to adjust for confounders. risk of death, 143.0% higher, RR 2.43, _p_ = 0.03, treatment 23 of 82 (28.0%), control 6 of 52 (11.5%). Kelly et al., 7/22/2020, retrospective, Ireland, Europe, peer-reviewed, 14 authors.Share Tweet
Submit Corrections or Comments7/21 Late
Bernaola et al., medRxiv, doi:10.1101/2020.07.17.20155960(Preprint)
death, ↓17.0%, p<0.0001 Observational Study of the Efficiency of Treatments in Patients Hospitalized with Covid-19 in Madrid Details HCQ HR 0.83 based on propensity score matched retrospective analysis of 1,645 hospitalized patients. Prednisone HR 0.85 , 14 other medications showed either no signicant benefit or a negative effect. 7/21 Details SourceLate treatment study Late treatment study Bernaola et al., medRxiv, doi:10.1101/2020.07.17.20155960
(Preprint)
Observational Study of the Efficiency of Treatments in Patients Hospitalized with Covid-19 in Madrid HCQ HR 0.83 based on propensity score matched retrospective analysis of 1,645 hospitalized patients. Prednisone HR 0.85 , 14 other medications showed either no signicant benefit or a negative effect. risk of death, 17.0% lower, RR 0.83, _p_ < 0.001, treatment 236 of 1498 (15.8%), control 28 of 147 (19.0%). Bernaola et al., 7/21/2020, retrospective, Spain, Europe, preprint, 7authors.
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Submit Corrections or Comments7/20 PrEP
Desbois et al., Research Square, doi:10.21203/rs.3.rs-41653/v1(Preprint)
cases, ↓16.9%, p=1.00 Prevalence and clinical features of COVID-19 in a large cohort of 199 patients with sarcoidosis Details Retrospective 199 sarcoidosis patients showing non-statistically significant HCQ RR 0.83, _p_=1.0. 7/20 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Desbois et al., Research Square, doi:10.21203/rs.3.rs-41653/v1
(Preprint)
Prevalence and clinical features of COVID-19 in a large cohort of 199 patients with sarcoidosis Retrospective 199 sarcoidosis patients showing non-statistically significant HCQ RR 0.83, _p_=1.0. risk of COVID-19 case, 16.9% lower, RR 0.83, _p_ = 1.00, treatment 3 of 27 (11.1%), control 23 of 172 (13.4%). Desbois et al., 7/20/2020, retrospective, France, Europe, preprint, mean age 58.8, 13 authors.Share Tweet
Submit Corrections or Comments7/20 Early
Risch, H., American Journal of Epidemiology, July 20, 2020, doi:10.1093/aje/kwaa152 (Peer Reviewed) (meta analysis - not includedin study count)
meta-analysis
Response to: “Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients” and “Re: Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis” Details Updated meta analysis including 7 new studies of high-risk outpatients, for a total of 12 studies, all showing significant benefit. 7/20 Details SourceEarly treatment study Early treatment study Risch, H., American Journal of Epidemiology, July 20, 2020, doi:10.1093/aje/kwaa152 (Peer Reviewed) (meta analysis - not included
in study count)
Response to: “Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients” and “Re: Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis” Updated meta analysis including 7 new studies of high-risk outpatients, for a total of 12 studies, all showing significantbenefit.
Risch et al., 7/20/2020, peer-reviewed, 1 author.Share Tweet
Submit Corrections or Comments7/18 PEP
Watanabe, M., arXiv.org, arXiv:2007.09477 (Preprint) (meta analysis - not included in study count)meta-analysis
Efficacy of Hydroxychloroquine as Prophylaxis for Covid-19 Details Secondary analysis of Boulware et al.'s PEP trial and treatment delay-response data, confirming that HCQ is effective when used early, _p_<0.01. The effectiveness found is especially notable considering the limitations of the study. Treatm.. 7/18 Details SourcePost Exposure Prophylaxis study Post Exposure Prophylaxis study Watanabe, M., arXiv.org, arXiv:2007.09477 (Preprint) (meta analysis - not included in study count) Efficacy of Hydroxychloroquine as Prophylaxis for Covid-19 Secondary analysis of Boulware et al.'s PEP trial and treatment delay-response data, confirming that HCQ is effective when used early,
_p_<0.01.
The effectiveness found is especially notable considering the limitations of the study. Treatment was relatively late, withenrollment up to
4 days after exposure, and an unspecified shipping delay. While the paper does not provide shipping details, the study protocol gives some detail allowing us to estimate the treatment delay as ~70 to 140 hours after exposure on average for the 1-4 days since enrollment specified in the paper (we will update this when authors respond to our request for details). There was only 75% medication adherence, including 16% who did not take the medication at all. The study relies on Internetsurveys.
Some issues have been raised with this analysis. 1-tailed vs. 2-tailed tests - this is debatable, an argument can be made for both cases. However, it doesn't affect the conclusion in terms of the delay-response relationship showing statistically significant efficacy. Secondly, the paper projects the "1-4" day results to a day "0" result (in reality about 46 hours later in all cases), while the trend may well continue, we do not know this. However it doesn't change the outcome that the 1-4 day results show a statistically significant delay-response relationship. Watanabe et al., 7/18/2020, preprint, 1 author.Share Tweet
Submit Corrections or Comments7/19 Late
McGrail et al., medRxiv, doi:10.1101/2020.07.17.20156521(Preprint)
death, ↑70.0%, p=0.69 COVID-19 Case Series at UnityPoint Health St. Luke’s Hospital inCedar Rapids, IA
Details HCQ+AZ early in the epidemic had a fairly good success rate with few complications, 86% of HCQ patients survived and 92% of HCQ+AZ patients. Patients not receiving either had 93% survival but were not considered comparable because the tre.. 7/19 Details SourceLate treatment study Late treatment study McGrail et al., medRxiv, doi:10.1101/2020.07.17.20156521 (Preprint) COVID-19 Case Series at UnityPoint Health St. Luke’s Hospital in
Cedar Rapids, IA
HCQ+AZ early in the epidemic had a fairly good success rate with few complications, 86% of HCQ patients survived and 92% of HCQ+AZ patients. Patients not receiving either had 93% survival but were not considered comparable because the treated groups were significantly more ill (100% hypoxic at admission vs. 59%) and this study does not adjust for the differences. Transition from an early intubation strategy to aggressive utilization of high flow nasal cannula and noninvasive ventilation (i.e, BiPAP) was successful in freeing up ICU resources. risk of death, 70.0% higher, RR 1.70, _p_ = 0.69, treatment 4 of 33 (12.1%), control 3 of 42 (7.1%). McGrail et al., 7/19/2020, retrospective, USA, North America, preprint, 2 authors.Share Tweet
Submit Corrections or Comments7/17 Late
Lyngbakken et al., Nature Communications, doi:10.1038/s41467-020-19056-6 (Peer Reviewed) death, ↓3.7%, p=1.00 A pragmatic randomized controlled trial reports lack of efficacy of hydroxychloroquine on coronavirus disease 2019 viral kinetics Details Small RCT of nasopharyngeal viral load not showing significant differences. The rate of reduction for HCQ was 0.24 RNA copies/mL/24h, and 0.14 for the control group (71% faster with HCQ but not statistically signi.. 7/17 Details SourceLate treatment study Late treatment study Lyngbakken et al., Nature Communications, doi:10.1038/s41467-020-19056-6 (Peer Reviewed) A pragmatic randomized controlled trial reports lack of efficacy of hydroxychloroquine on coronavirus disease 2019 viral kinetics Small RCT of nasopharyngeal viral load not showing significant differences. The rate of reduction for HCQ was 0.24 RNA copies/mL/24h, and 0.14 for the control group (71% faster with HCQ but not statistically significant with the small sample size of 27 HCQ and 26 control patients). Analysis only over 96 hours.
NCT04316377
risk of death, 3.7% lower, RR 0.96, _p_ = 1.00, treatment 1 of 27 (3.7%), control 1 of 26 (3.8%). improvement in viral load reduction rate, 71.0% lower, relative rate 0.29, _p_ = 0.51, treatment 27, control 26. Lyngbakken et al., 7/17/2020, Randomized Controlled Trial, Norway, Europe, peer-reviewed, median age 62.0, 11 authors.Share Tweet
Submit Corrections or Comments7/16 Early
Hong et al., Infect. Chemother., 2020, doi:10.3947/ic.2020.52.e43(Peer Reviewed)
viral+, ↓64.9%, p=0.001 Early Hydroxychloroquine Administration for Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Eradication Details HCQ 1-4 days from diagnosis was the only protective factor against prolonged viral shedding found, OR 0.111, _p_=0.001. 57.1% viral clearance with 1-4 days delay vs. 22.9% for 5+ days delayed treatment. Authors report that early administrat.. 7/16 Details SourceEarly treatment study Early treatment study Hong et al., Infect. Chemother., 2020, doi:10.3947/ic.2020.52.e43
(Peer Reviewed)
Early Hydroxychloroquine Administration for Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Eradication HCQ 1-4 days from diagnosis was the only protective factor against prolonged viral shedding found, OR 0.111, _p_=0.001. 57.1% viral clearance with 1-4 days delay vs. 22.9% for 5+ days delayed treatment. Authors report that early administration of HCQ significantly ameliorates inflammatory cytokine secretion and that COVID-19 patients should be administrated HCQ as soon as possible. 42 patients with HCQ 1-4 days from diagnosis, 48 with HCQ 5+ days from diagnosis. risk of prolonged viral shedding, 64.9% lower, RR 0.35, _p_ = 0.001, treatment 42, control 48, OR converted to RR. Hong et al., 7/16/2020, retrospective, South Korea, Asia, peer-reviewed, 7 authors, dosage not specified.Share Tweet
Submit Corrections or Comments7/16 Early
Skipper et al., Annals of Internal Medicine, doi:10.7326/M20-4207(Peer Reviewed)
hosp./death, ↓36.7%, p=0.58 Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19: ARandomized Trial
Details ~70 to 140 hour (inc. shipping) delayed outpatient treatment with HCQ showing lower hospitalization/death and faster recovery, but not reaching statistical significance. There was one hospitalized control death and one non-hospitalized HC.. 7/16 Details SourceEarly treatment study Early treatment study Skipper et al., Annals of Internal Medicine, doi:10.7326/M20-4207
(Peer Reviewed)
Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19: ARandomized Trial
~70 to 140 hour (inc. shipping) delayed outpatient treatment with HCQ showing lower hospitalization/death and faster recovery, but not reaching statistical significance. There was one hospitalized control death and one non-hospitalized HCQ death. It is unclear why there was a non-hospitalized death, external factors such as lack of standard care may be involved. Excluding that case results in one control death and zero HCQ deaths. Details for the hospitalizations and deaths such as medication adherence and treatment delay may be informative but arenot provided.
The paper states the end point was changed to symptom severity because they would have required 6,000 participants. However, if the same event rates continued, they would hit 95% significance on the reduction in hospitalization after adding less than 500 patients perarm.
Treatment is relatively late, ~70 to 140 hours after symptoms, including the shipping delay. The paper does not mention the shipping delay but partial details are provided in the study protocol. They are not clear but suggest no shipping on the weekends and a possible 12pm cutoff for same day dispensing and mailing. Assuming that enrollments were evenly distributed between 6am and 12am each day, we get an average of approximately 46 hours shipping delay. We have asked for shipping details and will update with more accurate values when available. In any case the treatment delay is relatively long and there is likely little overlap with the more typical delays used such as 0 - 36 hours for oseltamivir. The paper compares 0 - 36 hour delayed treatment with oseltamivir (influenza) and ~70 to 140 hour delayed treatment with HCQ (COVID-19), noting that oseltamivir seemed more effective. However, a more comparable study is McLean (2015) who showed that 48 - 119 hour delayed treatment with oseltamivir has no effect. This suggests that HCQ is more effective than oseltamivir, and that HCQ may still have significant effect for some amount of delay beyond the delay where oseltamivir is effective. 6 people were included that enrolled with >4d symptoms, although they do not match the study inclusion criteria. This reduces observed effectiveness. The paper says 56% (236) were enrolled within 1 day of symptoms, but results show only 40% for "<1d", 56% is possibly for <48hrs, we have asked for clarification. Patients in this study are relatively young and most of them recover without assistance. This reduces the room for a treatment to make improvements. The maximum improvement of an effective treatment would be expected before all patients approach recovery. Authors focus on the end result where most have recovered, but it is more informative to examine the curve and the point of maximum effectiveness. Authors did not collect data for every day but they do have interim results for days 3, 5, 10. The results are consistent with an effective treatment and show a statistically significant improvement, _p_ = 0.05, at day 10 (other unreported days might show increasedeffectiveness).
Results also show a larger treatment effect for those >50, not statistically significant due to the small sample, but noted as COVID-19 risk dramatically increases with age. The effect may be more visible here because younger patients may on average have more mild cases with less room for improvement. In general patients in this study have relatively mild symptoms on average, limiting the chance to observe improvement. The study relies on Internet surveys. Known fake surveys were submitted to the similar PEP trial and there could be an unknown number of undetected fake surveys in both trials. The study shows a high incidence of side effects in the placebo arm, which could be in part due to fake entries . The granularity change in the histograms of Figure S4 has raised questions . Data on increasing severity, less affected by the lower bound where everyone has recovered, also supports effectiveness . Research shows the placebo used in the US may be protective for COVID-19 so the true effectiveness of HCQ could be higher than observed. Also see . Treatment delay reporting has changed from the companion PEP trial which reported results for enrollment delays 1, 2, 3, and 4 separately (and from which we can confirm a statistically significant delay-response relationship), while this trial combines 1-2 and 3-4, and adds <1. Since the two trials share reporting (some patients were moved between trials) the reason for the differences are not clear. RCT of 423 patients with Internet surveys. Medication adherence was only 77% so the true effect of treatment is likely higher. Analysis of primarily low risk patients, authors note the results are not generalizable to the COVID high-risk population. We will update when hearing back on questions asked. Also see and regarding flaws in this study. NCT04308668. twitter.com/Covid19Crusher/status/1284515906375356416 twitter.com/Covid19Crusher/status/1284515906375356416 twitter.com/Covid19Crusher/status/1284515906375356416 frontiersin.org/articles/10.3389/fphar.2020.01062/full acpjournals.org/doi/full/10.7326/L21-0001 drive.google.com/file/d/1NZOJ57fM0RTaHD1t_9w2iua7lUJhOgWT/view twitter.com/cnpaiva/status/1303324404630388738 risk of combined hospitalization/death, 36.7% lower, RR 0.63, _p_ = 0.58, treatment 5 of 231 (2.2%), control 8 of 234 (3.4%), COVID-19 adjudicated hospitalization/death. risk of hospitalization, 49.4% lower, RR 0.51, _p_ = 0.38, treatment 4 of 231 (1.7%), control 8 of 234 (3.4%), COVID-19 adjudicatedhospitalization.
risk of combined hospitalization/death, 49.4% lower, RR 0.51, _p_ = 0.29, treatment 5 of 231 (2.2%), control 10 of 234 (4.3%), all hospitalization/death. risk of hospitalization, 59.5% lower, RR 0.41, _p_ = 0.17, treatment 4 of 231 (1.7%), control 10 of 234 (4.3%), all hospitalizations. risk of no recovery at day 14, 20.0% lower, RR 0.80, _p_ = 0.21. Skipper et al., 7/16/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 24 authors, dosage 800mg once, followed by 600mg in 6 to 8 hours, then 600mg daily for 4 more days.Share Tweet
Submit Corrections or Comments7/16 Early
Mitjà et al., Clinical Infectious Diseases, ciaa1009, doi:10.1093/cid/ciaa1009 (Peer Reviewed) hosp., ↓16.0%, p=0.64 Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial Details This paper has conflicting values, table S2 shows 12 control hospitalizations, while table 2 shows 11. The original report for this paper had more conflicting values, with values reported in Table 2 and the abstract corresponding to 12 co.. 7/16 Details SourceEarly treatment study Early treatment study Mitjà et al., Clinical Infectious Diseases, ciaa1009, doi:10.1093/cid/ciaa1009 (Peer Reviewed) Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial This paper has conflicting values, table S2 shows 12 control hospitalizations, while table 2 shows 11. The original report for this paper had more conflicting values, with values reported in Table 2 and the abstract corresponding to 12 control hospitalizations, while others corresponded to 11 control hospitalizations. The counts in table S2 also do not match - n=290 is given for secondary endpoints but the three groups add up to n=238. The sum of the secondary endpoint counts for the control group in table 2 do not match the group size. One missing patient may be the 12th control hospitalization but there are 2 more missing. There was a 16% reduction in hospitalization and 34% reduction in the risk of no symptom resolution, without statistical significance due to
small samples.
Treatment delay is unknown at this time. They report a delay of up to 120 hours after symptoms plus an additional unspecified delay where medication was provided to patients at the first home visit. We have asked for details of the treatment delay and will update when hearing back. They do not break down results by treatment delay. The paper does not mention zinc. Zinc deficiency in Spain has been reported at 83% , this may significantly reduce effectiveness. HCQ is a zinc ionophore which increases cellular uptake, facilitating significant intracellular concentrations of zinc, and zinc is known to inhibit SARS-CoV RNA-dependent RNA polymerase activity, and is widely thought to be important for effectiveness with SARS-CoV-2 . Undetectable viral load was changed to 3 log10 copies/mL potentially masking effectiveness. For viral load authors use nasopharyngeal swabs, we note that viral activity in the lung may be especially important for COVID-19, and that research has shown HCQ concentrations can be much higher in the lung compared to plasma . We also note that viral detection by PCR does not equate to viable virus . Accuracy of the tests is not provided. Nasopharyngeal viral load analysis issues include test unreliability and temporo-spatial differences in viral shedding . 293 low-risk patients with no deaths. No serious adverse events. We asked for more details on the treatment delay and viral load change but received no response. Also see this open letter: mdpi.com/2072-6643/9/7/697 infezmed.it/index.php/article?Anno=2020&numero=2&ArticoloDaVisualizzare=Vol_28_2_2020_192 ncbi.nlm.nih.gov/pmc/articles/PMC7122276/HCQ ams.edu.sg/view-pdf.aspx?file=media%5c5556_fi_331.pdf&ofile=Period+of+Infectivity+Position+Stateme.. journal.chestnet.org/article/S0012-3692(20)31718-9/fulltext drive.google.com/file/d/1NZOJ57fM0RTaHD1t_9w2iua7lUJhOgWT/view risk of hospitalization, 16.0% lower, RR 0.84, _p_ = 0.64, treatment 8 of 136 (5.9%), control 11 of 157 (7.0%). risk of no recovery, 34.0% lower, RR 0.66, _p_ = 0.38, treatment 8 of 136 (5.9%), control 14 of 157 (8.9%). relative change in viral load from baseline, 2.0% lower, relative load 0.98, treatment 136, control 157, day 7. Mitjà et al., 7/16/2020, Randomized Controlled Trial, Spain, Europe, peer-reviewed, 45 authors, dosage 800mg day 1, 400mg days 2-7.Share Tweet
Submit Corrections or Comments7/15 Late
Gupta et al., JAMA Intern. Med., doi:10.1001/jamainternmed.2020.3596 (Peer Reviewed) death, ↑6.0%, p=0.41 Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US Details Analysis of 2215 intensive care unit patients showing no significant differences with this very late stage use of HCQ. HCQ+AZ mortality relative risk RR 0.96, _p_=0.53, HCQ and HCQ+AZ combined RR 1.06, _p_=0.409. 7/15 Details SourceLate treatment study Late treatment study Gupta et al., JAMA Intern. Med., doi:10.1001/jamainternmed.2020.3596 (Peer Reviewed) Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US Analysis of 2215 intensive care unit patients showing no significant differences with this very late stage use of HCQ. HCQ+AZ mortality relative risk RR 0.96, _p_=0.53, HCQ and HCQ+AZ combined RR 1.06,
_p_=0.409.
risk of death, 6.0% higher, RR 1.06, _p_ = 0.41, treatment 631 of 1761 (35.8%), control 153 of 454 (33.7%). Gupta et al., 7/15/2020, retrospective, USA, North America, peer-reviewed, baseline oxygen requirements 87.1%, 34 authors.Share Tweet
Submit Corrections or Comments7/15 N/A
Kavanagh et al., Med. Hypotheses, doi:10.1016/j.mehy.2020.110110(Peer Reviewed)
dosing study
Inhaled hydroxychloroquine to improve efficacy and reduce harm in the treatment of COVID-19 Details Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliverthe..
7/15 Details SourceN/A
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Kavanagh et al., Med. Hypotheses, doi:10.1016/j.mehy.2020.110110(Peer Reviewed)
Inhaled hydroxychloroquine to improve efficacy and reduce harm in the treatment of COVID-19 Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the drug directly to the lungs at a lower dose than that required for oral systemic delivery. Kavanagh et al., 7/15/2020, peer-reviewed, 9 authors.Share Tweet
Submit Corrections or Comments7/14 Late
Trullàs et al., Research Square, doi:10.21203/rs.3.rs-39421/v1(Preprint)
death, ↓35.6%, p=0.12 High in-hospital mortality due to COVID-19 in a community hospital in Spain: a prospective observational study Details Retrospective 100 hospitalized patients in Spain showing lower mortality with HCQ+AZ. 7/14 Details SourceLate treatment study Late treatment study Trullàs et al., Research Square, doi:10.21203/rs.3.rs-39421/v1
(Preprint)
High in-hospital mortality due to COVID-19 in a community hospital in Spain: a prospective observational study Retrospective 100 hospitalized patients in Spain showing lower mortality with HCQ+AZ. risk of death, 35.6% lower, RR 0.64, _p_ = 0.12, treatment 20 of 66 (30.3%), control 16 of 34 (47.1%). Trullàs et al., 7/14/2020, retrospective, Spain, Europe, preprint, median age 75.0, 8 authors.Share Tweet
Submit Corrections or Comments7/14 Early
Chowdhury et al., Eurasian Journal of Medicine and Oncology, doi:10.14744/ejmo.2021.16263 (Peer Reviewed) A Randomized Trial of Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin therapy on COVID19 patients Details Small 116 patient RCT comparing ivermectin+doxycycline and HCQ+AZ, not showing a significant difference in time to PCR negative or symptom resolution. Time to symptomatic recovery was 5.93 days for ivermectin+doxycycline vs. 6.99days for..
7/14 Details SourceEarly treatment study Early treatment study Chowdhury et al., Eurasian Journal of Medicine and Oncology, doi:10.14744/ejmo.2021.16263 (Peer Reviewed) A Randomized Trial of Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin therapy on COVID19 patients Small 116 patient RCT comparing ivermectin+doxycycline and HCQ+AZ, not showing a significant difference in time to PCR negative or symptom resolution. Time to symptomatic recovery was 5.93 days for ivermectin+doxycycline vs. 6.99 days for HCQ+AZ. Given the long half-life of HCQ and the lack of a loading dose, it may take several days for HCQ to reach therapeutic levels. 10% of HCQ+AZ patients were lost to followup (2x ivermectin+doxycycline). There is no comparison with a control group. Chowdhury et al., 7/14/2020, peer-reviewed, 6 authors.
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Submit Corrections or Comments7/11 Late
Lecronier et al., Critical Care, 24:418, 2020, doi:10.1186/s13054-020-03117-9 (Peer Reviewed) death, ↓42.0%, p=0.24 Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis Details Retrospective 80 ICU patients, 22 SOC, 20 lopinavir/ritonavir, 38 HCQ. 28 day mortality 24% (HCQ) versus 41% (SOC), a 41% decrease, but not statistically significant due to very small sample sizes. No statistically significant differences.. 7/11 Details SourceLate treatment study Late treatment study Lecronier et al., Critical Care, 24:418, 2020, doi:10.1186/s13054-020-03117-9 (Peer Reviewed) Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis Retrospective 80 ICU patients, 22 SOC, 20 lopinavir/ritonavir, 38 HCQ. 28 day mortality 24% (HCQ) versus 41% (SOC), a 41% decrease, but not statistically significant due to very small sample sizes. No statistically significant differences found for treatment escalation, ventilator-free days, viral load, or mortality. Authors consider treatment escalation more important than mortality, for unknown
reasons.
risk of death, 42.0% lower, RR 0.58, _p_ = 0.24, treatment 9 of 38 (23.7%), control 9 of 22 (40.9%). risk of treatment escalation, 6.0% lower, RR 0.94, _p_ = 0.73, treatment 15 of 38 (39.5%), control 9 of 22 (40.9%). risk of viral+ at day 7, 15.0% lower, RR 0.85, _p_ = 0.61, treatment 19 of 26 (73.1%), control 12 of 14 (85.7%). Lecronier et al., 7/11/2020, retrospective, France, Europe, peer-reviewed, baseline oxygen requirements 100.0%, 25 authors, HCQvs. control.
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Submit Corrections or Comments7/10 Late
Cravedi et al., American Journal of Transplantation, doi:10.1111/ajt.16185 (Peer Reviewed) death, ↑53.0%, p=0.17 COVID‐19 and kidney transplantation: Results from the TANGO International Transplant Consortium Details Analysis of 144 hospitalized kidney transplant patients showing HCQ mortality HR 1.53, _p_ = 0.17. Subject to confounding by indication. 7/10 Details SourceLate treatment study Late treatment study Cravedi et al., American Journal of Transplantation, doi:10.1111/ajt.16185 (Peer Reviewed) COVID‐19 and kidney transplantation: Results from the TANGO International Transplant Consortium Analysis of 144 hospitalized kidney transplant patients showing HCQ mortality HR 1.53, _p_ = 0.17. Subject to confounding by indication. risk of death, 53.0% higher, RR 1.53, _p_ = 0.17, treatment 36 of 101 (35.6%), control 10 of 43 (23.3%). Cravedi et al., 7/10/2020, retrospective, USA, multiple countries, North America, multiple regions, peer-reviewed, mean age 60.0, 25
authors.
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Submit Corrections or Comments7/10 Late
Chen et al., PLoS ONE, doi:10.1371/journal.pone.0242763 (PeerReviewed)
viral+, ↓24.0%, p=0.71 A Multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate Coronavirus disease 2019 (COVID-19) Details 2 very small studies with hospitalized patients in Taiwan. RCT with 21 treatment and 12 SOC patients. No mortality, or serious adverse effects. Median time to negative RNA 5 days versus 10 days SOC, _p_=0.4. Risk of PCR+ at day14, RR 0.76..
7/10 Details SourceLate treatment study Late treatment study Chen et al., PLoS ONE, doi:10.1371/journal.pone.0242763 (Peer
Reviewed)
A Multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate Coronavirus disease 2019 (COVID-19) 2 very small studies with hospitalized patients in Taiwan. RCT with 21 treatment and 12 SOC patients. No mortality, or serious adverse effects. Median time to negative RNA 5 days versus 10 days SOC, _p_=0.4. Risk of PCR+ at day 14, RR 0.76, _p_ = 0.71. This paper also reports on a small retrospective study with 12 of 28 HCQ patients and 5 of 9 in the control group being PCR- at day 14, RR1.29, _p_ = 0.7.
risk of no virological cure, 24.0% lower, RR 0.76, _p_ = 0.71, treatment 4 of 21 (19.0%), control 3 of 12 (25.0%), day 14. median time to PCR-, 50.0% lower, relative time 0.50, _p_ = 0.40, treatment 21, control 12. Chen et al., 7/10/2020, Randomized Controlled Trial, Taiwan, Asia, peer-reviewed, 19 authors.Share Tweet
Submit Corrections or Comments7/9 Late
Rivera-Izquierdo et al., Medicina Clínica, doi:10.1016/j.medcli.2020.06.025 (Peer Reviewed) death, ↓19.0%, p=0.75 Agentes terapéuticos utilizados en 238 pacientes hospitalizados por COVID-19 y su relación con la mortalidad Details Retrospective 238 hospitalized patients in Spain showing lower mortality with HCQ, adjusted hazardratio aHR 0.81 .
7/9 Details SourceLate treatment study Late treatment study Rivera-Izquierdo et al., Medicina Clínica, doi:10.1016/j.medcli.2020.06.025 (Peer Reviewed) Agentes terapéuticos utilizados en 238 pacientes hospitalizados por COVID-19 y su relación con la mortalidad Retrospective 238 hospitalized patients in Spain showing lower mortality with HCQ, adjusted hazard ratio aHR 0.81 . risk of death, 19.0% lower, RR 0.81, _p_ = 0.75, treatment 215,
control 23.
Rivera et al., 7/9/2020, retrospective, Spain, Europe, peer-reviewed,21 authors.
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Raoult et al., Preprint (Preprint) (meta analysis - not includedin study count)
meta-analysis
Hydroxychloroquine and Azithromycin as a Treatment of COVID-19: Results of an Open-Label Non-Randomized Clinical Trial: Response to David Spencer (Elsevier) Details Updated meta analysis showing significant reductions in mortality and viral shedding. Mortality OR 0.53 for clinical studies, 0.92 big data studies, 18,211 patients. Persistent viral shedding OR 0.47 , 4,540patients.
7/9 Details SourceEarly, Late
Early, Late
Raoult et al., Preprint (Preprint) (meta analysis - not included instudy count)
Hydroxychloroquine and Azithromycin as a Treatment of COVID-19: Results of an Open-Label Non-Randomized Clinical Trial: Response to David Spencer (Elsevier) Updated meta analysis showing significant reductions in mortality and viral shedding. Mortality OR 0.53 for clinical studies, 0.92 big data studies, 18,211 patients. Persistent viral shedding OR 0.47 , 4,540 patients. Raoult et al., 7/9/2020, preprint, 7 authors.Share Tweet
Submit Corrections or Comments7/8 N/A
Marzolini et al., Antimicrobial Agents and Chemotherapy, doi:10.1128/AAC.01177-20 (Peer Reviewed) (not included in the studycount)
dosing study
Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations Details Study of Lopinivar and HCQ plasma concentrations and CRP levels in late stage (treatment initiation median 8 days from onset) COVID-19 patients. The median HCQ plasma concentration was 171 ng/ml, which authors suggest indicates thatHCQ l..
7/8 Details SourceN/A
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Marzolini et al., Antimicrobial Agents and Chemotherapy, doi:10.1128/AAC.01177-20 (Peer Reviewed) (not included in the studycount)
Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations Study of Lopinivar and HCQ plasma concentrations and CRP levels in late stage (treatment initiation median 8 days from onset) COVID-19 patients. The median HCQ plasma concentration was 171 ng/ml, which authors suggest indicates that HCQ levels achieved _in vivo_ do not result in adequate clinical activity for COVID-19, however this is incorrect as tissue concentration can be many times higher . c19study.com/ruiz.html Marzolini et al., 7/8/2020, peer-reviewed, 18 authors.Share Tweet
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Li et al., Cell Death & Disease volume 11, doi:10.1038/s41419-020-2721-8 (Review) (Peer Reviewed) (not includedin the study count)
review
Is hydroxychloroquine beneficial for COVID-19 patients? Details Review of the anti-inflammatory, antiviral, and protective vascular effects of CQ and HCQ, noting that HCQ may be preferable for COVID-19 due to fewer side effects. 7/8 Details SourceN/A
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Li et al., Cell Death & Disease volume 11, doi:10.1038/s41419-020-2721-8 (Review) (Peer Reviewed) (not includedin the study count)
Is hydroxychloroquine beneficial for COVID-19 patients? Review of the anti-inflammatory, antiviral, and protective vascular effects of CQ and HCQ, noting that HCQ may be preferable for COVID-19 due to fewer side effects. Li et al., 7/8/2020, peer-reviewed, 8 authors.Share Tweet
Submit Corrections or Comments7/7 Review
Goldstein, L., Preprint, July 7, 2020 (Review) (Preprint) (not included in the study count)review
Hydroxychloroquine-based COVID-19 Treatment, A Systematic Review of Clinical Evidence and Expert Opinion from Physicians’ Surveys Details 85% of globally surveyed physicians recognized HCQ as at least partially effective in treating COVID-19, according to Sermo W3. More than half of the surveyed US physicians would take the drug or give it to family members early or even be.. 7/7 Details SourceReview
Review
Goldstein, L., Preprint, July 7, 2020 (Review) (Preprint) (not included in the study count) Hydroxychloroquine-based COVID-19 Treatment, A Systematic Review of Clinical Evidence and Expert Opinion from Physicians’ Surveys 85% of globally surveyed physicians recognized HCQ as at least partially effective in treating COVID-19, according to Sermo W3. More than half of the surveyed US physicians would take the drug or give it to family members early or even before onset of symptoms, according toJC.
Aside from the rarely used plasma, HCQ / HCQ+AZ based treatments are preferred by physicians by wide margin over other drugs. HCQ / HCQ+AZ based treatments are the most used, most recommended, and most highly rated by physicians treating COVID-19 at an early stage. Goldstein et al., 7/7/2020, preprint, 1 author.Share Tweet
Submit Corrections or Comments7/7 Late
An et al., medRxiv, doi:10.1101/2020.07.04.20146548 (Preprint) viral+, ↓3.0%, p=0.92 Treatment Response to Hydroxychloroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea Details Retrospective of hospitalized patients with 31 HCQ patients and 195 standard treatment patients, not showing a significant difference in terms of viral clearance or recovery. There was no mortality in either group. "It is notable th.. 7/7 Details SourceLate treatment study Late treatment study An et al., medRxiv, doi:10.1101/2020.07.04.20146548 (Preprint) Treatment Response to Hydroxychloroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea Retrospective of hospitalized patients with 31 HCQ patients and 195 standard treatment patients, not showing a significant difference in terms of viral clearance or recovery. There was no mortality in either
group.
"It is notable that HQ plus antibiotics group had worse baseline clinical profiles (i.e. higher percentage of moderate severity patients, more patients with fever >=37.5C, higher average body temperature) and prognostic indicators such as age, LDH, lymphocytecount, and CRP".
We note that propensity score matching removed almost all of the male patients in the control group (40% -> 5%) but increased the percentage of male patients in the treatment group. This provides a large advantage to the control group because there is a very large difference in severity and mortality based on gender . In terms of viral RNA clearance we note that other research has found that "active viral replication drops quickly after the first week, and viable virus was not found after the second week of illness despite the persistence of PCR detection of RNA” . ncbi.nlm.nih.gov/pmc/articles/PMC7247289/ ams.edu.sg/view-pdf.aspx?file=media%5c5556_fi_331.pdf&ofile=Period+of+Infectivity+Position+Stateme.. time to viral clearance, 3.0% lower, RR 0.97, _p_ = 0.92, treatment31, control 195.
An et al., 7/7/2020, retrospective, South Korea, Asia, preprint, 12authors.
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Submit Corrections or Comments7/3 PrEP
Zhong et al., Lancent Rheumatology, 10.1016/S2665-9913(20)30227-7(Peer Reviewed)
cases, ↓91.0%, p=0.04 COVID-19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational study Details Rheumatic disease patients on HCQ had a lower risk of COVID-19 than those on other disease-modifying anti-rheumatic drugs, OR 0.09 (0.01–0.94), _p_=0.044 after adjusting for age, sex, smoking, systemic lupus erythematosus, infection inothe..
7/3 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Zhong et al., Lancent Rheumatology, 10.1016/S2665-9913(20)30227-7
(Peer Reviewed)
COVID-19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational study Rheumatic disease patients on HCQ had a lower risk of COVID-19 than those on other disease-modifying anti-rheumatic drugs, OR 0.09 (0.01–0.94), _p_=0.044 after adjusting for age, sex, smoking, systemic lupus erythematosus, infection in other family members, and comorbidities. 43 patients with rheumatic disease and COVID-19exposure.
risk of COVID-19 case, 91.0% lower, RR 0.09, _p_ = 0.04, treatment 7 of 16 (43.8%), control 20 of 27 (74.1%), adjusted. Zhong et al., 7/3/2020, retrospective, database analysis, China, Asia, peer-reviewed, 20 authors.Share Tweet
Submit Corrections or Comments7/1 Late
Arshad et al., Int. J. Infect. Dis., July 1 2020, doi:10.1016/j.ijid.2020.06.099 (Peer Reviewed) death, ↓51.3%, p=0.009 Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19 Details HCQ decreases mortality from 26.4% to 13.5% (HCQ) or 20.1% (HCQ+AZ). Propensity matched HCQ HR 0.487, _p_=0.009. Michigan 2,541 patients retrospective. Before propensity matching the HCQ group average age is 5 years younger and thepercenta..
7/1 Details SourceLate treatment study Late treatment study Arshad et al., Int. J. Infect. Dis., July 1 2020, doi:10.1016/j.ijid.2020.06.099 (Peer Reviewed) Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19 HCQ decreases mortality from 26.4% to 13.5% (HCQ) or 20.1% (HCQ+AZ). Propensity matched HCQ HR 0.487, _p_=0.009. Michigan 2,541 patients retrospective. Before propensity matching the HCQ group average age is 5 years younger and the percentage of male patients is 4% higher which is likely to favor the treatment and the control respectively in the before-propensity matching results. Some reported limtiations of this study are inaccurate . Corticosteroids were controlled for in the multivariate and propensity analyses as were age and comorbidities including cardiac disease and severity of illness. Age was an independent risk factor associated with mortality. HCQ was independently associated with decreased mortality, distinct from the steroid effect. 91% of all patients began treatment within two days of admission. HCQ was used throughout the study period, limiting time bias. Patients assigned to HCQ group had moderate and severe illness at presentation, which would favor worse
outcome with HCQ.
ijidonline.com/article/S1201-9712(20)30604-4/fulltext risk of death, 51.3% lower, RR 0.49, _p_ = 0.009, treatment 162 of 1202 (13.5%), control 108 of 409 (26.4%). Arshad et al., 7/1/2020, retrospective, USA, North America, peer-reviewed, 12 authors.Share Tweet
Submit Corrections or Comments7/1 N/A
Samuel et al., Heart Rhythm, doi:10.1016/j.hrthm.2020.06.033 (Peer Reviewed) (not included in the study count)safety analysis
Incidence of arrhythmias and electrocardiographic abnormalities in symptomatic pediatric patients with PCR positive SARS-CoV-2 infection including drug induced changes in the corrected QT interval (QTc) Details In pediatric patients with PCR positive active COVID-19 infection, significant arrhythmias are infrequent, but occur at an incidence higher than expected in a general pediatric population. Comorbidities are not more common in patients wit.. 7/1 Details SourceN/A
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Samuel et al., Heart Rhythm, doi:10.1016/j.hrthm.2020.06.033 (Peer Reviewed) (not included in the study count) Incidence of arrhythmias and electrocardiographic abnormalities in symptomatic pediatric patients with PCR positive SARS-CoV-2 infection including drug induced changes in the corrected QT interval (QTc) In pediatric patients with PCR positive active COVID-19 infection, significant arrhythmias are infrequent, but occur at an incidence higher than expected in a general pediatric population. Comorbidities are not more common in patients with arrhythmias than in patients without arrhythmias. However, providers still need to be vigilant for comorbidities that may independently place patients at risk for arrhythmias. COVID-19 treatment using HCQ leads to significant QTc prolongation, but was not associated with arrhythmias in pediatric patients. The long term sequelae of arrhythmia development in this population and their impact on outcome needs to be studied. Samuel et al., 7/1/2020, peer-reviewed, 7 authors.Share Tweet
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Martinez-Lopez et al., Blood Cancer Journal, doi:10.1038/s41408-020-00372-5 (Peer Reviewed) death, ↓33.0%, p=0.20 Multiple Myeloma and SARS-CoV-2 Infection: Clinical Characteristics and Prognostic Factors of Inpatient Mortality Details Retrospective 167 multiple myeloma patients in Spain. 6/30 Details SourceLate treatment study Late treatment study Martinez-Lopez et al., Blood Cancer Journal, doi:10.1038/s41408-020-00372-5 (Peer Reviewed) Multiple Myeloma and SARS-CoV-2 Infection: Clinical Characteristics and Prognostic Factors of Inpatient Mortality Retrospective 167 multiple myeloma patients in Spain. risk of death, 33.0% lower, RR 0.67, _p_ = 0.20, treatment 47 of 148 (31.8%), control 9 of 19 (47.4%). Martinez-Lopez et al., 6/30/2020, retrospective, Spain, Europe, peer-reviewed, median age 71.0, 25 authors.
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Mikami et al., J. Gen. Intern. Med., doi:10.1007/s11606-020-05983-z (Peer Reviewed) death, ↓47.0%, p<0.0001 Risk Factors for Mortality in Patients with COVID-19 in New YorkCity
Details HCQ decreases mortality, HR 0.53 (CI 0.41–0.67). IPTW adjustment does not significantly change HR 0.53 (0.41-0.68). Retrospective 6,000 patients in New York City. 6/30 Details SourceLate treatment study Late treatment study Mikami et al., J. Gen. Intern. Med., doi:10.1007/s11606-020-05983-z
(Peer Reviewed)
Risk Factors for Mortality in Patients with COVID-19 in New YorkCity
HCQ decreases mortality, HR 0.53 (CI 0.41–0.67). IPTW adjustment does not significantly change HR 0.53 (0.41-0.68). Retrospective 6,000 patients in New York City. risk of death, 47.0% lower, RR 0.53, _p_ < 0.001, treatment 575 of 2077 (27.7%), control 231 of 743 (31.1%), adjusted. Mikami et al., 6/30/2020, retrospective, USA, North America, peer-reviewed, 7 authors.Share Tweet
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Komissarov et al., medRxiv, doi:10.1101/2020.06.30.20143289(Preprint)
viral load, ↑25.0%, p=0.45 Hydroxychloroquine has no effect on SARS-CoV-2 load in nasopharynx of patients with mild form of COVID-19 Details Small late stage (7-10 days post symptoms) study of nasal swab RNA with 12 control and 33 patients, showing no significant differences (significant reduction in viral load is seen in both groups). The groups are not comparable, withsign..
6/30 Details SourceLate treatment study Late treatment study Komissarov et al., medRxiv, doi:10.1101/2020.06.30.20143289
(Preprint)
Hydroxychloroquine has no effect on SARS-CoV-2 load in nasopharynx of patients with mild form of COVID-19 Small late stage (7-10 days post symptoms) study of nasal swab RNA with 12 control and 33 patients, showing no significant differences (significant reduction in viral load is seen in both groups). The groups are not comparable, with significant differences seen between hospitalized and non-hospitalized patients. 9 of 10 hospitalized patients were in the HCQ group and only one in the control group. 2 additional control patients were added between the first and second version of this preprint (including the only hospitalized control patient). risk of viral load, 25.0% higher, RR 1.25, _p_ = 0.45, treatment 26,control 10.
Komissarov et al., 6/30/2020, retrospective, Russia, Asia, Europe, preprint, 8 authors.Share Tweet
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Sosa-García et al., Cir Cir. 2020, 88:5, 569-575, doi:10.24875/CIRU.20000675 (Peer Reviewed) death, ↑10.5%, p=1.00 Experience in the management of severe COVID-19 patients in anintensive care unit
Details Small retrospective study of 56 ICU patients in Mexico showing HCQ RR 1.1, _p_ = 1.0. 6/29 Details SourceLate treatment study Late treatment study Sosa-García et al., Cir Cir. 2020, 88:5, 569-575, doi:10.24875/CIRU.20000675 (Peer Reviewed) Experience in the management of severe COVID-19 patients in an
intensive care unit
Small retrospective study of 56 ICU patients in Mexico showing HCQ RR1.1, _p_ = 1.0.
risk of death, 10.5% higher, RR 1.11, _p_ = 1.00, treatment 7 of 38 (18.4%), control 3 of 18 (16.7%). Sosa et al., 6/29/2020, retrospective, Mexico, North America, peer-reviewed, baseline oxygen requirements 100.0%, 6 authors.Share Tweet
Submit Corrections or Comments6/29 PrEP
Ferreira et al., J. Medical Virology, July 9, 2020, doi:10.1002/jmv.26286 (preprint 6/29) (Peer Reviewed) cases, ↓47.1%, p<0.0001 Chronic treatment with hydroxychloroquine and SARS-CoV-2 infection Details Chronic treatment with HCQ provides protection against COVID, odds ratio 0.51 (0.37-0.70). The actual benefit is likely to be larger becasue research shows that the risk of COVID-19 for systemic autoimmune disease patients is much highe.. 6/29 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Ferreira et al., J. Medical Virology, July 9, 2020, doi:10.1002/jmv.26286 (preprint 6/29) (Peer Reviewed) Chronic treatment with hydroxychloroquine and SARS-CoV-2 infection Chronic treatment with HCQ provides protection against COVID, odds ratio 0.51 (0.37-0.70). The actual benefit is likely to be larger becasue research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall. Ferri et al. show OR 4.42, _p_<0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. c19study.com/ferri.html risk of COVID-19 case, 47.1% lower, RR 0.53, _p_ < 0.001, adjusted,
OR converted to RR.
Ferreira et al., 6/29/2020, retrospective, population-based cohort, database analysis, Portugal, Europe, peer-reviewed, 3 authors.Share Tweet
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Mfeukeu-Kuate et al. (Preprint) (not included in the study count)safety analysis
Electrocardiographic safety of daily Hydroxychloroquine 400mg plus Azithromycin 250mg as an ambulatory treatment for COVID-19 patients inCameroon
Details No life-threatening modifications of the QT interval was observed in non-severe COVID-19 patients treated ambulatory with HCQ+AZ. 51 relatively young patients 39 +/-11.
6/29 Details SourceN/A
N/A
Mfeukeu-Kuate et al. (Preprint) (not included in the study count) Electrocardiographic safety of daily Hydroxychloroquine 400mg plus Azithromycin 250mg as an ambulatory treatment for COVID-19 patients inCameroon
No life-threatening modifications of the QT interval was observed in non-severe COVID-19 patients treated ambulatory with HCQ+AZ. 51 relatively young patients 39 +/- 11. Mfeukeu-Kuate et al., 6/29/2020, preprint, 29 authors.Share Tweet
Submit Corrections or Comments6/25 PrEP
Gendebien et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-218244 (Letter) cases, ↓3.9%, p=0.93 Systematic analysis of COVID-19 infection and symptoms in a systemic lupus erythematosus population: correlation with disease characteristics, hydroxychloroquine use and immunosuppressivetreatments
Details Small study of 152 SLE patients taking HCQ with a phone survey for COVID-19 suggestive symptoms. There was 2 hospitalizations (group not identified) and no ICU or death cases. A similar percentage of suspected infections were reportedfor..
6/25 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Gendebien et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-218244 (Letter) Systematic analysis of COVID-19 infection and symptoms in a systemic lupus erythematosus population: correlation with disease characteristics, hydroxychloroquine use and immunosuppressive
treatments
Small study of 152 SLE patients taking HCQ with a phone survey for COVID-19 suggestive symptoms. There was 2 hospitalizations (group not identified) and no ICU or death cases. A similar percentage of suspected infections were reported for HCQ users and non-HCQ users, RR0.96, _p_ = 0.93.
There was no mortality and severity was not analyzed to determine if HCQ treated patients fared better. No adjustment for concomitant medications or severity of SLE. Only 5 cases were PCR confirmed. risk of COVID-19 case, 3.9% lower, RR 0.96, _p_ = 0.93, treatment 12 of 152 (7.9%), control 6 of 73 (8.2%). Gendebien et al., 6/25/2020, retrospective, Belgium, Europe, preprint, survey, 9 authors.Share Tweet
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Lagier et al., Travel Med. Infect. Dis. 101791, Jun 25, 2020, doi:10.1016/j.tmaid.2020.101791 (Peer Reviewed) death, ↓59.0%, p=0.05 Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis Details Early treatment leads to significantly better clinical outcome and faster viral load reduction. Matched sample mortality HR 0.41 p-value 0.048. Retrospective 3,737 patients. This study includes both outpatients and hospitalized patients. 6/25 Details SourceLate treatment study Late treatment study Lagier et al., Travel Med. Infect. Dis. 101791, Jun 25, 2020, doi:10.1016/j.tmaid.2020.101791 (Peer Reviewed) Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis Early treatment leads to significantly better clinical outcome and faster viral load reduction. Matched sample mortality HR 0.41 p-value 0.048. Retrospective 3,737 patients. This study includes both outpatients and hospitalized patients. risk of death, 59.0% lower, RR 0.41, _p_ = 0.05, treatment 35 of 3119 (1.1%), control 58 of 618 (9.4%), adjusted. Lagier et al., 6/25/2020, retrospective, France, Europe, peer-reviewed, 22 authors, dosage 200mg tid days 1-10.
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Bousquet et al., Aging, 12:12, 11306-11313, doi:10.18632/aging.103583 (Peer Reviewed) death, ↓42.8%, p=0.15 ADL-dependency, D-Dimers, LDH and absence of anticoagulation are independently associated with one-month mortality in older inpatientswith Covid-19
Details Observational prospective 108 hospitalized patients 65 and older, showing HCQ mortality OR 0.49, _p_= 0.15.
6/23 Details SourceLate treatment study Late treatment study Bousquet et al., Aging, 12:12, 11306-11313, doi:10.18632/aging.103583 (Peer Reviewed) ADL-dependency, D-Dimers, LDH and absence of anticoagulation are independently associated with one-month mortality in older inpatients
with Covid-19
Observational prospective 108 hospitalized patients 65 and older, showing HCQ mortality OR 0.49, _p_ = 0.15. risk of death, 42.8% lower, RR 0.57, _p_ = 0.15, treatment 5 of 27 (18.5%), control 23 of 81 (28.4%), adjusted, OR converted to RR. Bousquet et al., 6/23/2020, prospective, France, Europe, peer-reviewed, 10 authors.Share Tweet
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Isaksen et al., medRxiv, doi:10.1101/2020.06.19.20135475(Preprint)
safety analysis
Chloroquine, but not hydroxychlorquine, prolongs the QT interval in a primary care population Details Safety analysis in patients without COVID-19, finding a small increase in QTc associated with use of CQ, but not HCQ. Authors also study mortality (n=3,368), with HCQ hazardratio 0.67 .
6/22 Details SourceSafety
Safety
Isaksen et al., medRxiv, doi:10.1101/2020.06.19.20135475 (Preprint) Chloroquine, but not hydroxychlorquine, prolongs the QT interval in a primary care population Safety analysis in patients without COVID-19, finding a small increase in QTc associated with use of CQ, but not HCQ. Authors also study mortality (n=3,368), with HCQ hazard ratio 0.67 . Isaksen et al., 6/22/2020, preprint, 5 authors.Share Tweet
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Fontana et al., Clinical Kidney Journal, 13:3, 334–339, doi:10.1093/ckj/sfaa084 (Peer Reviewed) death, ↓50.0%, p=0.53 SARS-CoV-2 infection in dialysis patients in northern Italy: a single-centre experience Details Very small observational study of 15 dialysis patients showing HCQ mortality RR 0.50, _p_ = 0.53. 6/22 Details SourceLate treatment study Late treatment study Fontana et al., Clinical Kidney Journal, 13:3, 334–339, doi:10.1093/ckj/sfaa084 (Peer Reviewed) SARS-CoV-2 infection in dialysis patients in northern Italy: a single-centre experience Very small observational study of 15 dialysis patients showing HCQ mortality RR 0.50, _p_ = 0.53. risk of death, 50.0% lower, RR 0.50, _p_ = 0.53, treatment 4 of 12 (33.3%), control 2 of 3 (66.7%). Fontana et al., 6/22/2020, retrospective, Italy, Europe, peer-reviewed, 8 authors.
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Chen et al., medRxiv, doi:10.1101/2020.06.19.20136093 (Preprint) viral- time, ↓72.0%, p=0.01 Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomizedcontrolled study
Details Significantly faster clinical recovery and shorter time to RNA negative (from 7.0 days to 2.0 days (HCQ), _p_=0.01. 67 patients with mild/moderate cases. 6/22 Details SourceEarly treatment study Early treatment study Chen et al., medRxiv, doi:10.1101/2020.06.19.20136093 (Preprint) Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized
controlled study
Significantly faster clinical recovery and shorter time to RNA negative (from 7.0 days to 2.0 days (HCQ), _p_=0.01. 67 patients with mild/moderate cases. median time to PCR-, 72.0% lower, relative time 0.28, _p_ = 0.01, treatment 18, control 12. Chen et al., 6/22/2020, Randomized Controlled Trial, China, Asia, preprint, 19 authors, dosage 200mg bid days 1-10.Share Tweet
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Faíco-Filho et al., Braz J Microbiol, doi:10.1007/s42770-020-00395-x (preprint 6/21) (Peer Reviewed) viral rate, ↓80.8%, p=0.40 No benefit of hydroxychloroquine on SARS-CoV-2 viral load reduction in non-critical hospitalized patients with COVID-19 Details Viral load comparison for 34 HCQ and 32 control patients hospitalized with moderate COVID-19. All patients recovered limiting the room for beneficial effects. While not achieving statistical significance, results show faster recovery wi.. 6/21 Details SourceLate treatment study Late treatment study Faíco-Filho et al., Braz J Microbiol, doi:10.1007/s42770-020-00395-x (preprint 6/21) (Peer Reviewed) No benefit of hydroxychloroquine on SARS-CoV-2 viral load reduction in non-critical hospitalized patients with COVID-19 Viral load comparison for 34 HCQ and 32 control patients hospitalized with moderate COVID-19. All patients recovered limiting the room for
beneficial effects.
While not achieving statistical significance, results show faster recovery with HCQ. The greatest benefit is seen mid-recovery as expected for an effective treatment: Δt7-12: 81% improvement with HCQ Δt<7: 24% improvement with HCQ For Δt>12, everyone has recovered so there is no room for improvement. Since the HCQ group started slightly higher the improvement is slightly less. Most participants have also dropped out by this test, with only 6 HCQ and 9 control remaining (also suggesting HCQ patients recovered faster). Δt7-12 ΔCt improvement, 80.8% lower, relative rate 0.19, _p_ = 0.40, treatment 34, control 32. Δt<7 ΔCt improvement, 24.0% lower, relative rate 0.76, _p_ = 0.36, treatment 34, control 32. Δt>12 ΔCt improvement, 15.0% higher, relative rate 1.15, _p_ = 0.52, treatment 34, control 32. Faíco-Filho et al., 6/21/2020, prospective, Brazil, South America, peer-reviewed, median age 58.0, 6 authors.Share Tweet
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SMSH Sawai Man Singh Hospital, India (News) (not included in thestudy count)
news
HCQ beneficial as preventive drug: SMS doctors told ICMR Details PrEP with 4,300 very high risk healthcare workers in a hospital with up to 500+ COVID patients at a time, only 1% cases, all recovered. 6/19 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study SMSH Sawai Man Singh Hospital, India (News) (not included in the
study count)
HCQ beneficial as preventive drug: SMS doctors told ICMR PrEP with 4,300 very high risk healthcare workers in a hospital with up to 500+ COVID patients at a time, only 1% cases, all recovered. SMSH et al., 6/19/2020, preprint, 1 author.Share Tweet
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NIH, study not available yet (News) (not included in the studycount)
news
NIH halts clinical trial of hydroxychloroquine Details NIH halts late stage trial reporting no harm and no benefit. 470 patients. 6/19 Details SourceLate treatment study Late treatment study NIH, study not available yet (News) (not included in the study
count)
NIH halts clinical trial of hydroxychloroquine NIH halts late stage trial reporting no harm and no benefit. 470patients.
NIH et al., 6/19/2020, preprint, 1 author.Share Tweet
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Sbidian et al., medRxiv, doi:10.1101/2020.06.16.20132597(Preprint)
death, ↑5.0%, p=0.74 Hydroxychloroquine with or without azithromycin and in-hospital mortality or discharge in patients hospitalized for COVID-19 infection: a cohort study of 4,642 in-patients in France Details Retrospective of 4,642 hospitalized patients in France showing significantly faster discharge with HCQ and HCQ+AZ. No significant effect is seen on 28-day mortality, however many more control patients are still in hospital at 28 days. Oth.. 6/19 Details SourceLate treatment study Late treatment study Sbidian et al., medRxiv, doi:10.1101/2020.06.16.20132597 (Preprint) Hydroxychloroquine with or without azithromycin and in-hospital mortality or discharge in patients hospitalized for COVID-19 infection: a cohort study of 4,642 in-patients in France Retrospective of 4,642 hospitalized patients in France showing significantly faster discharge with HCQ and HCQ+AZ. No significant effect is seen on 28-day mortality, however many more control patients are still in hospital at 28 days. Other studies show faster resolution for HCQ, suggesting there will be a significant improvement when extending past 28 days. Hopefully authors will extend the analysis. Note that the median age is higher in the group not treated with HCQ
or AZ.
For other issues with the adjustments see . Also see the analysishere .
medrxiv.org/content/10.1101/2020.06.16.20132597v1#disqus_thread twitter.com/Covid19Crusher/status/1274668697408471040 risk of death, 5.0% higher, RR 1.05, _p_ = 0.74, treatment 111 of 623 (17.8%), control 830 of 3792 (21.9%), adjusted. risk of no hospital discharge, 20.0% lower, RR 0.80, _p_ = 0.002,adjusted.
Sbidian et al., 6/19/2020, retrospective, database analysis, France, Europe, preprint, 21 authors, whole population HCQ AIPTW adjusted.Share Tweet
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Kaptein et al., bioRxiv, doi:10.1101/2020.06.19.159053 (Peer Reviewed) (not included in the study count)animal study
Favipiravir at high doses has potent antiviral activity in SARS-CoV-2−infected hamsters, whereas hydroxychloroquine lacksactivity
Details Animal study with Syrian hamsters, showing treatment of SARS-CoV-2-infected hamsters with favipiravir or HCQ (with and without AZ). Treatment with HCQ alone resulted in a very modest reduction of 0.3 log10 viral RNA copies/mg lung, and no.. 6/19 Details SourceN/A
N/A
Kaptein et al., bioRxiv, doi:10.1101/2020.06.19.159053 (Peer Reviewed) (not included in the study count) Favipiravir at high doses has potent antiviral activity in SARS-CoV-2−infected hamsters, whereas hydroxychloroquine lacksactivity
Animal study with Syrian hamsters, showing treatment of SARS-CoV-2-infected hamsters with favipiravir or HCQ (with and without AZ). Treatment with HCQ alone resulted in a very modest reduction of 0.3 log10 viral RNA copies/mg lung, and no reduction in viral RNA load in the ileum or stool. Therapeutic levels of HCQ may not have been reached. Cytosolic concentrations in the lung were far below the EC90 target. A number of issues have reportedly been raised, including the following, for which the authors did not respond: - HCQ was administered with DMSO and Cremophor - why were non-neutral carriers chosen? DMSO has anti-inflammatory properties and Cremophor has a range of side effects : "use has been associated with severe anaphylactoid hypersensitivity reactions, hyperlipidemia, abnormal lipoprotein patterns, aggregation of erythrocytes and peripheral neuropathy". Why weren't the same amounts of solvent applied to the non-treated animals? Shouldn't favipiravir have been dissolved in the same way to avoid bias? - Why is the method of administration different for both products (oral gavage/intraperitoneal injection)? - One of the HCQ protocols used in France (IHU Marseille) prescribes 600mg of HCQ per day to patients. For a body weight of 60kg, this corresponds to a dose of 10mg/kg. How is a dose of 50 mg/kg in this study justified, i.e. 5 times more, with possible systemic effects on the animals and possible influence on the results? - Why were the animals killed after 4/5 days and did the treatment not continue? Unfortunately, this does not allow us to know the real course of the disease or the mortality of the animals beyond day 4. Is it because the animals spontaneously improve without treatment as Professor Neyts seems to say in his webinar for the GVN? And if this is indeed the case, isn't the use of these hamsters exactly an objection as a model for COVID-19 research? sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/cremophor Kaptein et al., 6/19/2020, peer-reviewed, 35 authors.Share Tweet
Submit Corrections or Comments6/18 Late
Paccoud et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa791 (Peer Reviewed) death, ↓11.0%, p=0.88 Compassionate use of hydroxychloroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital Details Retrospective of 89 hospitalized patients, survival HR 0.89 , not statistically significant. Authors note that unmeasured confounders may have persisted and the study may be underpowered. 6/18 Details SourceLate treatment study Late treatment study Paccoud et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa791 (Peer Reviewed) Compassionate use of hydroxychloroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital Retrospective of 89 hospitalized patients, survival HR 0.89 , not statistically significant. Authors note that unmeasured confounders may have persisted and the study may be
underpowered.
risk of death, 11.0% lower, RR 0.89, _p_ = 0.88, treatment 21 of 38 (55.3%), control 26 of 46 (56.5%), adjusted. Paccoud et al., 6/18/2020, retrospective, France, Europe, peer-reviewed, 20 authors.Share Tweet
Submit Corrections or Comments6/17 Early
Capucci et al., J. Cardiovasc. Med. 21, 922–923, doi:10.2459/JCM.0000000000001061 (Peer Reviewed) Low hospitalization rate without severe arrhythmias: a prospective survey on 350 patients early home treated with hydroxychloroquine during COVID-19 pandemic Details Prospective analysis of early treatment of 350 patients in Italy (without waiting for PCR results), showing low hospitalization rates and no serious adverse events. From 274 patients treated with HCQ, 16 required hospitalization (5.8%). .. 6/17 Details SourceEarly treatment study Early treatment study Capucci et al., J. Cardiovasc. Med. 21, 922–923, doi:10.2459/JCM.0000000000001061 (Peer Reviewed) Low hospitalization rate without severe arrhythmias: a prospective survey on 350 patients early home treated with hydroxychloroquine during COVID-19 pandemic Prospective analysis of early treatment of 350 patients in Italy (without waiting for PCR results), showing low hospitalization rates and no serious adverse events. From 274 patients treated with HCQ, 16 required hospitalization (5.8%). Minor complications (mainly gastrointestinal, diarrhoea) were found in eight patients (2.9%), none of whom had to interrupt treatment. No major cardiac complications were found. Of the 76 patients treated with HCQ+AZ, 4 were hospitalized (5.2%). Minor complications occurred in two patients (2.6%). There were no reports of any major arrhythmias, syncope or sudden death. Capucci et al., 6/17/2020, peer-reviewed, 7 authors.
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Xue et al., J. Med. Virology, June 17, 2020, doi:10.1002/jmv.26193(Peer Reviewed)
Hydroxychloroquine treatment in COVID-19: a descriptive observational analysis of 30 cases from a single center in Wuhan,China
Details 30 hospitalized patients. Early use of HCQ is more effective, 43% reduction in progression from moderate to severe. "Early" is relative here, within 7 days of hospitalization. 6/17 Details SourceLate treatment study Late treatment study Xue et al., J. Med. Virology, June 17, 2020, doi:10.1002/jmv.26193
(Peer Reviewed)
Hydroxychloroquine treatment in COVID-19: a descriptive observational analysis of 30 cases from a single center in Wuhan,China
30 hospitalized patients. Early use of HCQ is more effective, 43% reduction in progression from moderate to severe. "Early" is relative here, within 7 days of hospitalization. Xue et al., 6/17/2020, peer-reviewed, 7 authors.Share Tweet
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Luo et al., Annals of Oncology, 31:10, 1386-1396, doi:10.1016/j.annonc.2020.06.007 (Peer Reviewed) death, ↑2.2%, p=0.99 COVID-19 in patients with lung cancer Details Analysis of hospitalized lung cancer patients with 35 of 48 taking HCQ, mortality OR 1.03, _p_ = 0.99. 6/17 Details SourceLate treatment study Late treatment study Luo et al., Annals of Oncology, 31:10, 1386-1396, doi:10.1016/j.annonc.2020.06.007 (Peer Reviewed) COVID-19 in patients with lung cancer Analysis of hospitalized lung cancer patients with 35 of 48 taking HCQ, mortality OR 1.03, _p_ = 0.99. risk of death, 2.2% higher, RR 1.02, _p_ = 0.99, treatment 11 of 35 (31.4%), control 4 of 13 (30.8%), OR converted to RR. Luo et al., 6/17/2020, retrospective, USA, North America, peer-reviewed, 31 authors.
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Kim et al., Korean J Intern Med, doi:10.3904/kjim.2020.224 (PeerReviewed)
Lopinavir-ritonavir versus hydroxychloroquine for viral clearance and clinical improvement in patients with mild to moderate coronavirusdisease 2019
Details Small retrospective study of hospitalized patients with 31 lopinavir-ritonavir and 34 HCQ patients, HCQ 400mg once per day, finding no significant difference in clinical response, but more rapid viral clearance with lopinavir-ritonavir. 6/16 Details SourceLate treatment study Late treatment study Kim et al., Korean J Intern Med, doi:10.3904/kjim.2020.224 (Peer
Reviewed)
Lopinavir-ritonavir versus hydroxychloroquine for viral clearance and clinical improvement in patients with mild to moderate coronavirusdisease 2019
Small retrospective study of hospitalized patients with 31 lopinavir-ritonavir and 34 HCQ patients, HCQ 400mg once per day, finding no significant difference in clinical response, but more rapid viral clearance with lopinavir-ritonavir. Kim et al., 6/16/2020, retrospective, South Korea, Asia, peer-reviewed, 7 authors.Share Tweet
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WHIP COVID-19 (News) (not included in the study count)news
Henry Ford Health System still moving forward with hydroxychloroquine study Details Ongoing WHIP COVID-19 HCQ PrEP study reports analyzing their data and seeing a significantly improved outcome in a group of COVID-19 patients who received HCQ. For more details on the study see . 6/16 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study WHIP COVID-19 (News) (not included in the study count) Henry Ford Health System still moving forward with hydroxychloroquine study Ongoing WHIP COVID-19 HCQ PrEP study reports analyzing their data and seeing a significantly improved outcome in a group of COVID-19 patients who received HCQ. For more details on the study see . henryford.com/whip-covid-19 WHIP et al., 6/16/2020, preprint, 1 author.
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Huang et al., Annals of the Rheumatic Diseases 2020:79, 1163-1169, doi:10.1136/annrheumdis-2020-217425 (Peer Reviewed) hosp., ↓80.0%, p<0.001 Clinical characteristics of 17 patients with COVID-19 and systemic autoimmune diseases: a retrospective study Details Analysis of 1255 COVID-19 patients in Wuhan Tongji Hospital finding 0.61% with systemic autoimmune diseases, much lower than authors expected (3%–10%). Authors hypothesise that protective factors, such as CQ/HCQ use, reduce hospitalization. 6/16 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Huang et al., Annals of the Rheumatic Diseases 2020:79, 1163-1169, doi:10.1136/annrheumdis-2020-217425 (Peer Reviewed) Clinical characteristics of 17 patients with COVID-19 and systemic autoimmune diseases: a retrospective study Analysis of 1255 COVID-19 patients in Wuhan Tongji Hospital finding 0.61% with systemic autoimmune diseases, much lower than authors expected (3%–10%). Authors hypothesise that protective factors, such as CQ/HCQ use, reduce hospitalization. risk of hospitalization, 80.0% lower, RR 0.20, _p_ < 0.001, treatment
8, control 1247.
Huang et al., 6/16/2020, retrospective, China, Asia, peer-reviewed,15 authors.
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Submit Corrections or Comments6/12 Theory
Scherrmann, AAPS J 22, 86 (2020), doi:10.1208/s12248-020-00465-w (Peer Reviewed) (Theory) (not included in the study count)theory
Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxychloroquine-Azithromycin Combination inCOVID-19 Therapy
Details Theory paper, not included in the study count or percentages. Proposes a new mechanism supporting the synergistic interaction between HCQ+AZ. 6/12 Details SourceTheory
Theory
Scherrmann, AAPS J 22, 86 (2020), doi:10.1208/s12248-020-00465-w (Peer Reviewed) (Theory) (not included in the study count) Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxychloroquine-Azithromycin Combination inCOVID-19 Therapy
Theory paper, not included in the study count or percentages. Proposes a new mechanism supporting the synergistic interactionbetween HCQ+AZ.
Scherrmann et al., 6/12/2020, peer-reviewed, 1 author.Share Tweet
Submit Corrections or Comments6/12 Late
Giacomelli et al., Journal of Medical Virology, doi:10.1002/jmv.26407 (preprint 6/12) (Peer Reviewed) Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: a retrospective cohort study Details Late stage study of hospitalized patients comparing treatment starting within 5 days versus later. Note that "early" here is only relative - all patients are hospitalized so this is "late" and "very late". Th.. 6/12 Details SourceLate treatment study Late treatment study Giacomelli et al., Journal of Medical Virology, doi:10.1002/jmv.26407 (preprint 6/12) (Peer Reviewed) Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: a retrospective cohort study Late stage study of hospitalized patients comparing treatment starting within 5 days versus later. Note that "early" here is only relative - all patients are hospitalized so this is "late" and "very late". The "early" treatment group is significantly older. Severe adverse events attributed by authors to concurrent administration of LPV, making it difficult to make conclusions about HCQ. Giacomelli et al., 6/12/2020, peer-reviewed, 20 authors.
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Submit Corrections or Comments6/10 Late
Wang et al., medRxiv, doi:10.1101/2020.06.11.20128926 (PeerReviewed)
death, ↓5.8%, p=0.63 Comorbidity and Sociodemographic determinants in COVID-19 Mortality in an US Urban Healthcare System Details Database analysis of 7,592 patients in NYC, showing adjusted HCQ mortality odds ratio OR 0.96, _p_ = 0.82, and HCQ+AZ OR 0.94, _p_ = 0.63 6/10 Details SourceLate treatment study Late treatment study Wang et al., medRxiv, doi:10.1101/2020.06.11.20128926 (Peer
Reviewed)
Comorbidity and Sociodemographic determinants in COVID-19 Mortality in an US Urban Healthcare System Database analysis of 7,592 patients in NYC, showing adjusted HCQ mortality odds ratio OR 0.96, _p_ = 0.82, and HCQ+AZ OR 0.94, _p_ =0.63
risk of death, 5.8% lower, RR 0.94, _p_ = 0.63, treatment 1866, control 5726, OR converted to RR. Wang et al., 6/10/2020, retrospective, database analysis, USA, North America, peer-reviewed, 3 authors.Share Tweet
Submit Corrections or Comments6/10 Early
Otea et al., medRxiv, doi:10.1101/2020.06.10.20101105 (Preprint) A short therapeutic regimen based on hydroxychloroquine plus azithromycin for the treatment of COVID-19 in patients with non-severe disease. A strategy associated with a reduction in hospital admissionsand complications.
Details 80 moderate cases, HCQ+AZ appears to reduce serious complications and death. Moderate treated cases resulted in hospitalization at the same rate as mild untreated cases suggesting efficacy. 6/10 Details SourceEarly treatment study Early treatment study Otea et al., medRxiv, doi:10.1101/2020.06.10.20101105 (Preprint) A short therapeutic regimen based on hydroxychloroquine plus azithromycin for the treatment of COVID-19 in patients with non-severe disease. A strategy associated with a reduction in hospital admissions
and complications.
80 moderate cases, HCQ+AZ appears to reduce serious complications and death. Moderate treated cases resulted in hospitalization at the same rate as mild untreated cases suggesting efficacy. Otea et al., 6/10/2020, preprint, 6 authors.Share Tweet
Submit Corrections or Comments6/9 Early
Pirnay et al., Hosp. Pharm. and Clinician, doi:10.1016/j.phclin.2020.06.001 (Peer Reviewed) Beneficial effect of Hydroxychloroquine-Azithromycin combination in the treatment of elderly patients with Covid-19: results of anobservational study
Details 68 very high risk nursing home residents, median age 86, HCQ+AZ early treatment within 2.5 days onset, 2 stopped due to QTc. Only 7 died, significantly less than other nursing homes in France and the same as the median death for thesame ..
6/9 Details SourceEarly treatment study Early treatment study Pirnay et al., Hosp. Pharm. and Clinician, doi:10.1016/j.phclin.2020.06.001 (Peer Reviewed) Beneficial effect of Hydroxychloroquine-Azithromycin combination in the treatment of elderly patients with Covid-19: results of an
observational study
68 very high risk nursing home residents, median age 86, HCQ+AZ early treatment within 2.5 days onset, 2 stopped due to QTc. Only 7 died, significantly less than other nursing homes in France and the same as the median death for the same period in 2019/2018. Pirnay et al., 6/9/2020, peer-reviewed, 13 authors.Share Tweet
Submit Corrections or Comments6/9 PrEP
Bhattacharya et al., medRxix, doi:10.1101/2020.06.09.20116806(Preprint)
cases, ↓80.7%, p=0.001 Pre exposure Hydroxychloroquine use is associated with reduced COVID19 risk in healthcare workers Details HCQ reduced cases from 38% to 7%. 106 people. No serious adverse effects. 6/9 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Bhattacharya et al., medRxix, doi:10.1101/2020.06.09.20116806
(Preprint)
Pre exposure Hydroxychloroquine use is associated with reduced COVID19 risk in healthcare workers HCQ reduced cases from 38% to 7%. 106 people. No serious adverseeffects.
risk of COVID-19 case, 80.7% lower, RR 0.19, _p_ = 0.001, treatment 4 of 54 (7.4%), control 20 of 52 (38.5%). Bhattacharya et al., 6/9/2020, retrospective, India, South Asia, preprint, 7 authors.Share Tweet
Submit Corrections or Comments6/6 Review
Roussel et al., New Microbes and New Infections, Volume 38, doi:10.1016/j.nmni.2020.100710 (Review) (Peer Reviewed) (not includedin the study count)
review
Influence of conflicts of interest on public positions in the COVID-19 era, the case of Gilead Sciences Details Shows a correlation (Spearman test, _p_ = 0.017) between the amount received from Gilead Sciences and public opposition to the use of HCQ in France. 6/6 Details SourceReview
Review
Roussel et al., New Microbes and New Infections, Volume 38, doi:10.1016/j.nmni.2020.100710 (Review) (Peer Reviewed) (not includedin the study count)
Influence of conflicts of interest on public positions in the COVID-19 era, the case of Gilead Sciences Shows a correlation (Spearman test, _p_ = 0.017) between the amount received from Gilead Sciences and public opposition to the use of HCQin France.
Roussel et al., 6/6/2020, peer-reviewed, 2 authors.Share Tweet
Submit Corrections or Comments6/6 Early, Late
Million et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100709 (Peer Reviewed) (meta analysis - not included in study count)meta-analysis
Clinical Efficacy of Chloroquine derivatives in COVID-19 Infection: Comparative metaanalysis between the Big data and the real world Details CQ effective and reduces mortality by a factor 3. Meta analysis of 20 studies. 6/6 Details SourceEarly, Late
Early, Late
Million et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100709 (Peer Reviewed) (meta analysis - not included in study count) Clinical Efficacy of Chloroquine derivatives in COVID-19 Infection: Comparative metaanalysis between the Big data and the real world CQ effective and reduces mortality by a factor 3. Meta analysis of20 studies.
Million et al., 6/6/2020, peer-reviewed, 14 authors.Share Tweet
Submit Corrections or Comments6/5 Late
RECOVERY Collaborative Group, NEJM, doi:10.1056/NEJMoa2022926 (press release 6/5) (Preprint) death, ↑9.0%, p=0.15 Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized,controlled trial
Details RECOVERY trial finds no significant benefit for very late stage very sick patients. Results may be due to the unusually high dosage used (9.2g total over 10 days) . The overall dosage used is only 23% less than the high dosage tha.. 6/5 Details SourceLate treatment study Late treatment study RECOVERY Collaborative Group, NEJM, doi:10.1056/NEJMoa2022926 (press release 6/5) (Preprint) Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized,
controlled trial
RECOVERY trial finds no significant benefit for very late stage very sick patients. Results may be due to the unusually high dosage used (9.2g total over 10 days) . The overall dosage used is only 23% less than the high dosage that Borba et al. show greatly increases risk (OR 2.8) . Authors do not report results based on weight, BMI, or related conditions such as diabetes, which may provide additional evidence of toxic dosages. Authors do not adjust dosage based on patient weight, so toxicity may be higher in patients of lower weight. KM curves show a spike in HCQ mortality days 5-8, corresponding to ~85% of the total excess seen at day 28 (a similar spike is seen in the SOLIDARITY trial). Authors will not release the data until Jan 8, 2021. Authors note: "we did not observe excess mortality in the first 2 days of treatment ... when early effects of dose-dependent toxicity might be expected", but they are ignoring the very long half-life of HCQ and the dosing regimen - much higher levels of HCQ will be reached later. Increased mortality in Borba et al. occurred after 2 days. Patients were extremely sick (median 9 days post symptoms, 60% requiring oxygen and an additional 17% requiring ventilation/ECMO), and an unusually high death rate was seen in both arms. 1,561 HCQ patients, 3,155 SOC. A secondary analysis has found several inconsistencies in the data: . Hypoxia may inhibit HCQ entering cells , making it less effective for late stage use. For more on the dosing problems see , also noting that concentrations vary substantially in different tissues and lung concentration may be >30x plasma concentration. twitter.com/JamesTodaroMD/status/1272661099985481733 twitter.com/JamesTodaroMD/status/1276245669372723200 c19study.com/borba.html francesoir.fr/politique-monde/oxford-etude-recovery-ou-sont-les-morts twitter.com/JaclynHord/status/1302704076573077507 kristianfranciscomillanielsen.medium.com/analysis-of-the-hydroxychloroquine-dosing-regimen-in-reco.. risk of death, 9.0% higher, RR 1.09, _p_ = 0.15, treatment 421 of 1561 (27.0%), control 790 of 3155 (25.0%). RECOVERY et al., 6/5/2020, Randomized Controlled Trial, United Kingdom, Europe, preprint, 29 authors.Share Tweet
Submit Corrections or Comments6/3 PEP
Boulware et al., NEJM, June 3 2020, doi:10.1056/NEJMoa2016638(Peer Reviewed)
cases, ↓17.0%, p=0.35 A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19 Details COVID-19 cases are reduced by respectively when taken within ~ hours of exposure (including shipping delay). The treatment delay-response relationship is significant at _p_=0.002. PEP delayed treatment RCT.For..
6/3 Details SourcePost Exposure Prophylaxis study Post Exposure Prophylaxis study Boulware et al., NEJM, June 3 2020, doi:10.1056/NEJMoa2016638 (Peer
Reviewed)
A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19 COVID-19 cases are reduced by respectively when taken within ~ hours of exposure (including shipping delay). The treatment delay-response relationship is significant at _p_=0.002. PEP delayed treatment RCT. For more detailed analysis, see . 6 independent analyses of the data in this study confirm efficacy: . Regarding the use of folic acid, see . c19study.com/boulware.html drive.google.com/file/d/1NZOJ57fM0RTaHD1t_9w2iua7lUJhOgWT/view arxiv.org/abs/2007.09477 medrxiv.org/content/10.1101/2020.08.19.20178376v1 researchgate.net/publication/344369617_Hydroxychloroquine_as_Post-Exposure_Prophylaxis_for_Covid-1.. blog.philbirnbaum.com/2020/08/the-nejm-hydroxychloroquine-study-fails.html longdom.org/open-access/hydroxychloroquine-and-interferons-for-the-prophylaxis-and-early-treatment..osf.io/vz8a7/
sciencedirect.com/science/article/abs/pii/S0306987721000578 risk of COVID-19 case, 17.0% lower, RR 0.83, _p_ = 0.35, treatment 49 of 414 (11.8%), control 58 of 407 (14.3%). risk of COVID-19 case, 25.1% lower, RR 0.75, _p_ = 0.22, treatment 32 of 414 (7.7%), control 42 of 407 (10.3%), probable COVID-19 cases. Boulware et al., 6/3/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 24 authors.Share Tweet
Submit Corrections or Comments6/1 N/A
Al-Kofahi et al., Clin. Pharmacol. Ther., Jun 1, 2020, doi:10.1002/cpt.1874 (Peer Reviewed) (not included in the study count)dosing study
Finding the Dose for Hydroxychloroquine Prophylaxis for COVID‐19: The Desperate Search for Effectiveness Details Analysis of HCQ dosing regimens, recommending: PrEP: 800mg loading dose followed by 400mg 2 or 3 times weekly to maintain weekly troughs above EC50 in >50% of patients at steady-state. PEP: 800mg loading dose followed in 6 hours by 600m.. 6/1 Details SourceN/A
N/A
Al-Kofahi et al., Clin. Pharmacol. Ther., Jun 1, 2020, doi:10.1002/cpt.1874 (Peer Reviewed) (not included in the study count) Finding the Dose for Hydroxychloroquine Prophylaxis for COVID‐19: The Desperate Search for Effectiveness Analysis of HCQ dosing regimens, recommending: PrEP: 800mg loading dose followed by 400mg 2 or 3 times weekly to maintain weekly troughs above EC50 in >50% of patients atsteady-state.
PEP: 800mg loading dose followed in 6 hours by 600mg, then 600mg daily for 4 more days to achieve daily troughs above EC50 in >50% subjects. Al-Kofahi et al., 6/1/2020, peer-reviewed, 9 authors.Share Tweet
Submit Corrections or Comments5/31 Early
Guérin et al., Asian J. Medicine and Health, July 15, 2020, doi:10.9734/ajmah/2020/v18i730224 (preprint 5/31) (Peer Reviewed) death, ↓61.4%, p=1.00 Azithromycin and Hydroxychloroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19 Details Mean clinical recovery time reduced from 26 days (SOC) to 9 days, _p_<0.0001 (HCQ+AZ) or 13 days, _p_<0.0001 (AZ). No cardiac toxicity. Small retrospective study of 88 patients with case control analysis with matched patients. 5/31 Details SourceEarly treatment study Early treatment study Guérin et al., Asian J. Medicine and Health, July 15, 2020, doi:10.9734/ajmah/2020/v18i730224 (preprint 5/31) (Peer Reviewed) Azithromycin and Hydroxychloroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19 Mean clinical recovery time reduced from 26 days (SOC) to 9 days, _p_<0.0001 (HCQ+AZ) or 13 days, _p_<0.0001 (AZ). No cardiac toxicity. Small retrospective study of 88 patients with case control analysis with matched patients. risk of death, 61.4% lower, RR 0.39, _p_ = 1.00, treatment 0 of 20 (0.0%), control 1 of 34 (2.9%), continuity correction due to zero
event.
recovery time, 65.0% lower, relative time 0.35, _p_ < 0.001, treatment 20, control 34. Guérin et al., 5/31/2020, retrospective, France, Europe, peer-reviewed, 8 authors, dosage 600mg days 1-10, 7-10 days.Share Tweet
Submit Corrections or Comments5/28 Late
Chamieh et al., medRxiv 2020.05.28.20114835, doi:10.1101/2020.05.28.20114835 (Preprint) Viral Dynamics Matter in COVID-19 Pneumonia: the success of early treatment with hydroxychloroquine and azithromycin in Lebanon Details HCQ+AZ potentially explains 94.7% success in treating a fairly complex cohort. 5/28 Details SourceLate treatment study Late treatment study Chamieh et al., medRxiv 2020.05.28.20114835, doi:10.1101/2020.05.28.20114835 (Preprint) Viral Dynamics Matter in COVID-19 Pneumonia: the success of early treatment with hydroxychloroquine and azithromycin in Lebanon HCQ+AZ potentially explains 94.7% success in treating a fairly
complex cohort.
Chamieh et al., 5/28/2020, preprint, 10 authors.Share Tweet
Submit Corrections or Comments5/28 PrEP
Chatterjee et al., Indian J. Med. Res., June 20, 2020, doi:10.4103/ijmr.IJMR_2234_20 (Peer Reviewed) cases, ↓66.8%, p<0.001 Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19 Details 4+ doses of HCQ associated with a significant decline in the odds of getting infected, dose-response relationship exists. 5/28 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Chatterjee et al., Indian J. Med. Res., June 20, 2020, doi:10.4103/ijmr.IJMR_2234_20 (Peer Reviewed) Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19 4+ doses of HCQ associated with a significant decline in the odds of getting infected, dose-response relationship exists. risk of COVID-19 case, 66.8% lower, RR 0.33, _p_ < 0.001, treatment 12 of 68 (17.6%), control 206 of 387 (53.2%), full course vs. unused. Chatterjee et al., 5/28/2020, retrospective, India, South Asia, peer-reviewed, survey, 11 authors.
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Submit Corrections or Comments5/28 Late
Huang et al., National Science Review, nwaa113, doi:10.1093/nsr/nwaa113 (Peer Reviewed) viral- time, ↓67.0%, p<0.0001 Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment ofCOVID-19
Details 197 CQ patients, 176 control. Mean time to undetectable viral RNA and duration of fever significantly reduced. No serious adverse events. 5/28 Details SourceLate treatment study Late treatment study Huang et al., National Science Review, nwaa113, doi:10.1093/nsr/nwaa113 (Peer Reviewed) Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of
COVID-19
197 CQ patients, 176 control. Mean time to undetectable viral RNA and duration of fever significantly reduced. No serious adverse events. time to viral-, 67.0% lower, relative time 0.33, _p_ < 0.001, treatment 197, control 176. time to viral-, 59.1% lower, relative time 0.41, _p_ < 0.001, treatment 32, control 37, early treatment. Huang et al., 5/28/2020, prospective, China, Asia, peer-reviewed, 36authors.
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Submit Corrections or Comments5/27 Late
Goldman et al., NEJM, doi:10.1056/NEJMoa2015301 (Peer Reviewed) death, ↓22.3%, p=0.46 Remdesivir for 5 or 10 Days in Patients with Severe Covid-19 Details Study focused on remdesivir but with results for HCQ in the supplementary appendix, showing 9% death with HCQ versus 12% control, unadjusted relative risk uRR 0.78, _p_ = 0.46. 5/27 Details SourceLate treatment study Late treatment study Goldman et al., NEJM, doi:10.1056/NEJMoa2015301 (Peer Reviewed) Remdesivir for 5 or 10 Days in Patients with Severe Covid-19 Study focused on remdesivir but with results for HCQ in the supplementary appendix, showing 9% death with HCQ versus 12% control, unadjusted relative risk uRR 0.78, _p_ = 0.46. risk of death, 22.3% lower, RR 0.78, _p_ = 0.46, treatment 10 of 109 (9.2%), control 34 of 288 (11.8%). Goldman et al., 5/27/2020, retrospective, multiple countries, multiple regions, peer-reviewed, 26 authors.
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Submit Corrections or Comments5/28 Late
Kuderer et al., Lancet, June 20, 2020, doi:10.1016/S0140-6736(20)31187-9 (preprint 5/28) (Peer Reviewed) death, ↑134.2%, p<0.0001 Clinical impact of COVID-19 on patients with cancer (CCC19): acohort study
Details Retrospective 928 cancer patients, showing HCQ OR 1.06 . HCQ+AZ OR 2.93 . The relative risks of different therapies suggest that the results are overly affected by confounding by indication. Authors note: HCQ+AZmigh..
5/28 Details SourceLate treatment study Late treatment study Kuderer et al., Lancet, June 20, 2020, doi:10.1016/S0140-6736(20)31187-9 (preprint 5/28) (Peer Reviewed) Clinical impact of COVID-19 on patients with cancer (CCC19): a
cohort study
Retrospective 928 cancer patients, showing HCQ OR 1.06 . HCQ+AZ OR 2.93 . The relative risks of different therapies suggest that the results are overly affected by confounding by indication. Authors note: HCQ+AZ might not be the cause of increased mortality, but instead these were given to patients with more severeCOVID-19.
risk of death, 134.2% higher, RR 2.34, _p_ < 0.001, treatment 45 of 181 (24.9%), control 121 of 928 (13.0%), OR converted to RR, HCQ+AZ. Kuderer et al., 5/28/2020, retrospective, USA, multiple countries, North America, multiple regions, peer-reviewed, 73 authors.Share Tweet
Submit Corrections or Comments5/28 PrEP
Gianfrancesco et al., Annals of the Rheumatic Diseases, 79:7, 859-866, doi:10.1136/annrheumdis-2020-217871 (Peer Reviewed) hosp., ↓3.3%, p=0.82 Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry Details Analysis of rheumatic disease patients showing no significant association between antimalarial therapy and hospitalisation, OR=0.94 , _p_=0.82 afteradjustments.
5/28 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Gianfrancesco et al., Annals of the Rheumatic Diseases, 79:7, 859-866, doi:10.1136/annrheumdis-2020-217871 (Peer Reviewed) Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry Analysis of rheumatic disease patients showing no significant association between antimalarial therapy and hospitalisation, OR=0.94 , _p_=0.82 after adjustments. risk of hospitalization, 3.3% lower, RR 0.97, _p_ = 0.82, treatment 58 of 130 (44.6%), control 219 of 470 (46.6%), OR converted to RR. Gianfrancesco et al., 5/28/2020, retrospective, database analysis, multiple countries, multiple regions, peer-reviewed, 28 authors.
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Submit Corrections or Comments5/27 Early
Risch, American Journal of Epidemiology, kwaa093, 27 May 2020, doi:10.1093/aje/kwaa093 (Peer Reviewed) (meta analysis - not includedin study count)
meta-analysis
Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the PandemicCrisis
Details Five studies, including two controlled clinical trials, have demonstrated significant outpatient treatmentefficacy.
5/27 Details SourceEarly treatment study Early treatment study Risch, American Journal of Epidemiology, kwaa093, 27 May 2020, doi:10.1093/aje/kwaa093 (Peer Reviewed) (meta analysis - not included
in study count)
Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the PandemicCrisis
Five studies, including two controlled clinical trials, have demonstrated significant outpatient treatment efficacy. Risch et al., 5/27/2020, peer-reviewed, 1 author.Share Tweet
Submit Corrections or Comments5/25 Late
Ip et al., PLoS ONE, doi:10.1371/journal.pone.0237693 (PeerReviewed)
death, ↓1.0%, p=0.93 Hydroxychloroquine and Tocilizumab Therapy in COVID-19 Patients - An Observational Study Details Retrospective study of late stage use on 2,512 hospitalized patients showing no significant differences in associated mortality for patients receiving any HCQ during the hospitalization (HR, 0.99 ), HCQ alone (HR, 1.02 .. 5/25 Details SourceLate treatment study Late treatment study Ip et al., PLoS ONE, doi:10.1371/journal.pone.0237693 (Peer
Reviewed)
Hydroxychloroquine and Tocilizumab Therapy in COVID-19 Patients - An Observational Study Retrospective study of late stage use on 2,512 hospitalized patients showing no significant differences in associated mortality for patients receiving any HCQ during the hospitalization (HR, 0.99 ), HCQ alone (HR, 1.02 ), or HCQ+AZ (HR, 0.98 ). Misclassification is possible due to manual abstraction of EHR data. They observed a change in the prescribing patterns of HCQ during the study timeframe. Confounding byindication.
risk of death, 1.0% lower, RR 0.99, _p_ = 0.93, treatment 432 of 1914 (22.6%), control 115 of 598 (19.2%), adjusted. Ip et al., 5/25/2020, retrospective, database analysis, USA, North America, peer-reviewed, 32 authors.Share Tweet
Submit Corrections or Comments5/24 Late
Hraiech et al., Ann. Intensive Care, doi:10.1186/s13613-020-00678-4 (Peer Reviewed) death, ↓64.7%, p=0.21 Lack of viral clearance by the combination of hydroxychloroquine and azithromycin or lopinavir and ritonavir in SARS-CoV-2-related acute respiratory distress syndrome Details Retrospective 45 ICU patients, 17 treated with HCQ+AZ, showing no significant difference in viral clearance after 6 days, or mortality 6 days from ARDS. 5/24 Details SourceLate treatment study Late treatment study Hraiech et al., Ann. Intensive Care, doi:10.1186/s13613-020-00678-4
(Peer Reviewed)
Lack of viral clearance by the combination of hydroxychloroquine and azithromycin or lopinavir and ritonavir in SARS-CoV-2-related acute respiratory distress syndrome Retrospective 45 ICU patients, 17 treated with HCQ+AZ, showing no significant difference in viral clearance after 6 days, or mortality 6days from ARDS.
risk of death, 64.7% lower, RR 0.35, _p_ = 0.21, treatment 2 of 17 (11.8%), control 5 of 15 (33.3%), day 38 +- 7. risk of death, 376.5% higher, RR 4.76, _p_ = 0.49, treatment 2 of 17 (11.8%), control 0 of 15 (0.0%), continuity correction due to zero event, day 6 from ARDS. risk of no virological cure, 2.9% higher, RR 1.03, _p_ = 1.00, treatment 14 of 17 (82.4%), control 8 of 10 (80.0%), day 6 fromtreatment.
Hraiech et al., 5/24/2020, retrospective, France, Europe, peer-reviewed, 8 authors.Share Tweet
Submit Corrections or Comments5/22 PEP, PrEP
ICMR, Indian Council of Medical Research (Advisory) (not includedin the study count)
advisory
Revised advisory on the use of Hydroxychloroquine (HCQ) as prophylaxis for SARS-CoV-2 infection Details Healthcare workers on HCQ prophylaxis less likely to get COVID. Significant dose-response relationship. Extends recommended HCQ prophylaxis to asymptomatic household contacts of cases and frontline workers. Degree of benefit not quantified. 5/22 Details SourcePEP, PrEP
PEP, PrEP
ICMR, Indian Council of Medical Research (Advisory) (not includedin the study count)
Revised advisory on the use of Hydroxychloroquine (HCQ) as prophylaxis for SARS-CoV-2 infection Healthcare workers on HCQ prophylaxis less likely to get COVID. Significant dose-response relationship. Extends recommended HCQ prophylaxis to asymptomatic household contacts of cases and frontline workers. Degree of benefit not quantified. ICMR et al., 5/22/2020, preprint, 1 author.Share Tweet
Submit Corrections or Comments5/22 Late
Mehra et al., The Lancet, May 22, 2020, doi: 10.1016/S0140-6736(20)31180-6 (Peer Reviewed) (not included in thestudy count)
retracted
Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis Details Incorrect at first read (implausible death, ventilation, and population numbers). This paper was retracted. 5/22 Details SourceLate treatment study Late treatment study Mehra et al., The Lancet, May 22, 2020, doi: 10.1016/S0140-6736(20)31180-6 (Peer Reviewed) (not included in the
study count)
Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis Incorrect at first read (implausible death, ventilation, and population numbers). This paper was retracted. Mehra et al., 5/22/2020, peer-reviewed, 4 authors.Share Tweet
Submit Corrections or Comments5/19 Late
Singh et al., medRxiv, doi:10.1101/2020.05.12.20099028 (Preprint) death, ↓5.0%, p=0.72 Outcomes of Hydroxychloroquine Treatment Among Hospitalized COVID-19 Patients in the United States- Real-World Evidence From a Federated Electronic Medical Record Network Details EHR analysis of 3,372 hospitalized COVID-19 patients not showing a significant difference for mortality or the risk of mechanical ventilation. Subject to the limitations of EHR analysis. Misclassification is possible. Confounding by indic.. 5/19 Details SourceLate treatment study Late treatment study Singh et al., medRxiv, doi:10.1101/2020.05.12.20099028 (Preprint) Outcomes of Hydroxychloroquine Treatment Among Hospitalized COVID-19 Patients in the United States- Real-World Evidence From a Federated Electronic Medical Record Network EHR analysis of 3,372 hospitalized COVID-19 patients not showing a significant difference for mortality or the risk of mechanical ventilation. Subject to the limitations of EHR analysis. Misclassification is possible. Confounding by indication. risk of death, 5.0% lower, RR 0.95, _p_ = 0.72, treatment 104 of 910 (11.4%), control 109 of 910 (12.0%). risk of mechanical ventilation, 19.0% lower, RR 0.81, _p_ = 0.26, treatment 46 of 910 (5.1%), control 57 of 910 (6.3%). Singh et al., 5/19/2020, retrospective, database analysis, USA, North America, preprint, 4 authors.
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Kim et al., medRxiv, doi:10.1101/2020.05.13.20094193 (Preprint) hosp. time, ↓51.0%, p=0.01 Treatment Response to Hydroxychloroquine, Lopinavir/Ritonavir, and Antibiotics for Moderate COVID 19: A First Report on the Pharmacological Outcomes from South Korea Details Retrospective of 97 moderate cases. Time to viral clearance significantly shorter for HCQ+antibiotic. Preprint withdrawn pending peer review. 5/18 Details SourceLate treatment study Late treatment study Kim et al., medRxiv, doi:10.1101/2020.05.13.20094193 (Preprint) Treatment Response to Hydroxychloroquine, Lopinavir/Ritonavir, and Antibiotics for Moderate COVID 19: A First Report on the Pharmacological Outcomes from South Korea Retrospective of 97 moderate cases. Time to viral clearance significantly shorter for HCQ+antibiotic. Preprint withdrawn pending
peer review.
hospitalization time, 51.0% lower, relative time 0.49, _p_ = 0.01, treatment 22, control 40. time to viral-, 56.0% lower, relative time 0.44, _p_ = 0.005, treatment 22, control 40. Kim et al., 5/18/2020, retrospective, South Korea, Asia, preprint, 11authors.
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Ahmad et al., doi:10.1101/2020.05.18.20066902 (Preprint) Doxycycline and Hydroxychloroquine as Treatment for High-Risk COVID-19 Patients: Experience from Case Series of 54 Patients in Long-Term Care Facilities Details 54 patients in long term care facilities. 6% death with HCQ+AZ compared to 22% using a naive indirectcomparison.
5/18 Details SourceEarly treatment study Early treatment study Ahmad et al., doi:10.1101/2020.05.18.20066902 (Preprint) Doxycycline and Hydroxychloroquine as Treatment for High-Risk COVID-19 Patients: Experience from Case Series of 54 Patients in Long-Term Care Facilities 54 patients in long term care facilities. 6% death with HCQ+AZ compared to 22% using a naive indirect comparison. Ahmad et al., 5/18/2020, preprint, 5 authors.
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Macias et al., medRxiv, 10.1101/2020.05.16.20104141 (Preprint) hosp., ↓25.5%, p=1.00 Similar incidence of Coronavirus Disease 2019 (COVID-19) in patients with rheumatic diseases with and without hydroxychloroquinetherapy
Details Very small retrospective study of rheumatic disease patients, sample size is too small for statistical significance (HCQ 0.5-4.0%, no-HCQ 0.4-2.7%). Confirmed cases were 1 HCQ and 2 no-HCQ, confirmed+likely cases were 1 HCQ and 3 no-HCQ. .. 5/16 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Macias et al., medRxiv, 10.1101/2020.05.16.20104141 (Preprint) Similar incidence of Coronavirus Disease 2019 (COVID-19) in patients with rheumatic diseases with and without hydroxychloroquine
therapy
Very small retrospective study of rheumatic disease patients, sample size is too small for statistical significance (HCQ 0.5-4.0%, no-HCQ 0.4-2.7%). Confirmed cases were 1 HCQ and 2 no-HCQ, confirmed+likely cases were 1 HCQ and 3 no-HCQ. 1 HCQ and 2 no-HCQ patients were admitted to hospital. We do not think a conclusion can be drawn based on these sample sizes. There are very significant differences between the groups, for example 30% of the HCQ group have SLE vs. 2.5% of the no-HCQ group. SLE patients have a 5.7 times relative risk of pneumonia according to , whereas the relative risk with glucocorticoids and TNF-α inhibitors is significantly lower . Two more recent studies with rheumatic disease/autoimmune condition patients provide higher confidence. ncbi.nlm.nih.gov/pmc/articles/PMC4516647/ academic.oup.com/rheumatology/article/52/1/53/1830871 risk of hospitalization, 25.5% lower, RR 0.74, _p_ = 1.00, treatment 1 of 290 (0.3%), control 2 of 432 (0.5%). risk of COVID-19 case, 49.0% higher, RR 1.49, _p_ = 0.53, treatment 5 of 290 (1.7%), control 5 of 432 (1.2%). Macias et al., 5/16/2020, retrospective, database analysis, Spain, Europe, preprint, 12 authors.Share Tweet
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Yu et al., Science China Life Sciences, 2020 May 15, 1-7, doi:10.1007/s11427-020-1732-2 (Peer Reviewed) death, ↓60.5%, p=0.002 Low Dose of Hydroxychloroquine Reduces Fatality of Critically Ill Patients With COVID-19 Details Retrospective, 550 critically ill patients. 19% fatality for HCQ versus 47% for non-HCQ, RR 0.395, _p_=0.002. The levels of inflammatory cytokine IL-6 were significantly reduced from 22.2 pg/mL to 5.2 pg/mL (_p_<0.05) at the end of the treat.. 5/15 Details SourceLate treatment study Late treatment study Yu et al., Science China Life Sciences, 2020 May 15, 1-7, doi:10.1007/s11427-020-1732-2 (Peer Reviewed) Low Dose of Hydroxychloroquine Reduces Fatality of Critically Ill Patients With COVID-19 Retrospective, 550 critically ill patients. 19% fatality for HCQ versus 47% for non-HCQ, RR 0.395, _p_=0.002. The levels of inflammatory cytokine IL-6 were significantly reduced from 22.2 pg/mL to 5.2 pg/mL (_p_<0.05) at the end of the treatment in the HCQ group but there was no change in the control group. risk of death, 60.5% lower, RR 0.40, _p_ = 0.002, treatment 9 of 48 (18.8%), control 238 of 502 (47.4%). Yu et al., 5/15/2020, retrospective, China, Asia, peer-reviewed, 8
authors.
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Mahévas et al., BMJ 2020, 369, doi: https://doi.org/10.1136/bmj.m1844 (Peer Reviewed) death, ↑20.0%, p=0.75 Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study usingroutine care data
Details Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HCQ. Power of study appears too low to support conclusions . None of the 15 patients receiving HCQ+AZ were transferred to intensive care.. 5/14 Details SourceLate treatment study Late treatment study Mahévas et al., BMJ 2020, 369, doi: https://doi.org/10.1136/bmj.m1844 (Peer Reviewed) Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using
routine care data
Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HCQ. Power of study appears too low to support conclusions . None of the 15 patients receiving HCQ+AZ were transferred to intensive care or died compared to 23% overall. bmj.com/content/369/bmj.m1844/rapid-responses risk of death, 20.0% higher, RR 1.20, _p_ = 0.75, treatment 9 of 84 (10.7%), control 8 of 89 (9.0%), adjusted. Mahévas et al., 5/14/2020, retrospective, France, Europe, peer-reviewed, 34 authors.Share Tweet
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Okour et al., Journal of Pharmacokinetics and Pharmacodynamics, May 13, 2020, doi:10.1007/s10928-020-09689-x (Peer Reviewed) Hydroxychloroquine and azithromycin as potential treatments for COVID-19; clinical status impacts the outcome Details Odds of PCR-positive decrease by 53% for each unit increase in HCQ log-concentration. Similarly, the odds decrease by 61%, and by 12% for each day increase, and for azithromycin co-treatment, respectively. Computes the minimum HCQconcent..
5/13 Details SourceLate treatment study Late treatment study Okour et al., Journal of Pharmacokinetics and Pharmacodynamics, May 13, 2020, doi:10.1007/s10928-020-09689-x (Peer Reviewed) Hydroxychloroquine and azithromycin as potential treatments for COVID-19; clinical status impacts the outcome Odds of PCR-positive decrease by 53% for each unit increase in HCQ log-concentration. Similarly, the odds decrease by 61%, and by 12% for each day increase, and for azithromycin co-treatment, respectively. Computes the minimum HCQ concentration needed based on severity, and corresponding dosage regimens. A loading dose is found to be important. For LRTI and URTI patients the addition of AZ is needed. Extended analysis of Gautret et al. using the observed HCQ concentrations and pharmacokinetic analysis to compute concentrations
for all days.
Okour et al., 5/13/2020, peer-reviewed, 3 authors.Share Tweet
Submit Corrections or Comments5/12 PrEP
Cassione et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-217717 (Letter) cases, ↑49.6%, p=0.59 COVID-19 infection in a northern-Italian cohort of systemic lupus erythematosus assessed by telemedicine Details Survey of 165 SLE patients, 127 on HCQ. 8 patients with suspected COVID-19 and 4 confirmed cases. No mortality, one ICU case. 7 patients had no symptoms despite contact with a COVID-19 patient. No adjustment for concomitant medications o.. 5/12 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Cassione et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-217717 (Letter) COVID-19 infection in a northern-Italian cohort of systemic lupus erythematosus assessed by telemedicine Survey of 165 SLE patients, 127 on HCQ. 8 patients with suspected COVID-19 and 4 confirmed cases. No mortality, one ICU case. 7 patients had no symptoms despite contact with a COVID-19 patient. No adjustment for concomitant medications or severity of SLE. Confounding by indication. risk of COVID-19 case, 49.6% higher, RR 1.50, _p_ = 0.59, treatment 10 of 127 (7.9%), control 2 of 38 (5.3%). Cassione et al., 5/12/2020, retrospective, Italy, Europe, preprint, survey, median age 52.5, 6 authors.
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Shabrawishi et al., medRxix, doi:10.1101/2020.05.08.20095679(Preprint)
viral+, ↓14.7%, p=0.66 Negative nasopharyngeal SARS-CoV-2 PCR conversion in response to different therapeutic interventions Details Retrospective 93 hospitalized patients in Saudi Arabia showing a non-statistically significant 15% reduction in PCR positive results at day 5, RR 0.85, _p_ = 0.65. The treatment group had significantly more severe illness andsignificantly ..
5/11 Details SourceLate treatment study Late treatment study Shabrawishi et al., medRxix, doi:10.1101/2020.05.08.20095679
(Preprint)
Negative nasopharyngeal SARS-CoV-2 PCR conversion in response to different therapeutic interventions Retrospective 93 hospitalized patients in Saudi Arabia showing a non-statistically significant 15% reduction in PCR positive results at day 5, RR 0.85, _p_ = 0.65. The treatment group had significantly more severe illness and significantly more male patients. risk of no virological cure at day 5, 14.7% lower, RR 0.85, _p_ = 0.66, treatment 12 of 45 (26.7%), control 15 of 48 (31.2%). Shabrawishi et al., 5/11/2020, retrospective, Saudi Arabia, Middle East, preprint, mean age 43.9, 5 authors.Share Tweet
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Rosenberg et al., JAMA, May 11, 2020, doi:10.1001/jama.2020.8630(Peer Reviewed)
death, ↑35.0%, p=0.31 Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State Details Restrospective observational late stage study showing no significant differences but calling for clinical trials. Zervos et al. point out serious limitations that they say should be corrected on the record: patients receiving HCQwit..
5/11 Details SourceLate treatment study Late treatment study Rosenberg et al., JAMA, May 11, 2020, doi:10.1001/jama.2020.8630
(Peer Reviewed)
Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State Restrospective observational late stage study showing no significant differences but calling for clinical trials. Zervos et al. point out serious limitations that they say should be corrected on the record: patients receiving HCQ with or without AZ were overall sicker on presentation and had multiple other risk factors including much higher risk based on ethnicity; patients receiving HCQ were more likely to be obese, diabetic, have chronic lung disease, and cardiovascular conditions; yet these sicker patients had approximately the same mortality rates compared to patients with a milder course of the disease and less risk factors. However, the authors conclude that "there are no significant benefits." It is noteworthy that HCQ was associated with a significant survival benefit in a larger cohort of patients from New York City as reported byMikami et al .
See also .
ijidonline.com/article/S1201-9712(20)30604-4/fulltext c19study.com/mikami.html worldtribune.com/effectiveness-of-hydroxychloroquine-was-hiding-in-plain-sight/ risk of death, 35.0% higher, RR 1.35, _p_ = 0.31, treatment 189 of 735 (25.7%), control 28 of 221 (12.7%), adjusted. risk of death, 8.0% higher, RR 1.08, _p_ = 0.79, treatment 54 of 271 (19.9%), control 28 of 221 (12.7%), adjusted. Rosenberg et al., 5/11/2020, retrospective, USA, North America, peer-reviewed, 14 authors.Share Tweet
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Alberici et al., Kidney Int., 98:1, 20-26, July 1, 2020, doi:10.1016/j.kint.2020.04.030 (preprint 5/10) (Peer Reviewed) death, ↓42.9%, p=0.12 A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection Details Analysis of 94 hemodialysis COVID-19 positive patients. Reduction in death seen with HCQ but _p_=0.12, OR0.44 .
5/10 Details SourceLate treatment study Late treatment study Alberici et al., Kidney Int., 98:1, 20-26, July 1, 2020, doi:10.1016/j.kint.2020.04.030 (preprint 5/10) (Peer Reviewed) A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection Analysis of 94 hemodialysis COVID-19 positive patients. Reduction in death seen with HCQ but _p_=0.12, OR 0.44 . risk of death, 42.9% lower, RR 0.57, _p_ = 0.12, treatment 17 of 72 (23.6%), control 9 of 22 (40.9%), OR converted to RR. Alberici et al., 5/10/2020, retrospective, Italy, Europe, peer-reviewed, 31 authors.
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Grassin-Delyle et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa546 (Peer Reviewed) (Ex Vivo) (not included in thestudy count)
_ex vivo_
Chloroquine Inhibits the Release of Inflammatory Cytokines by HumanLung Explants
Details On human lung parenchymal explants, CQ concentration clinically achievable in the lung (100 µM) inhibited the lipopolysaccharide-induced release of TNF-ɑ (by 76%), IL-6 (by 68%), CCL2 (by 72%), and CCL3 (by 67%). In addition toantiviral ..
5/8 Details SourceEx Vivo
Ex Vivo
Grassin-Delyle et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa546 (Peer Reviewed) (Ex Vivo) (not included in thestudy count)
Chloroquine Inhibits the Release of Inflammatory Cytokines by HumanLung Explants
On human lung parenchymal explants, CQ concentration clinically achievable in the lung (100 µM) inhibited the lipopolysaccharide-induced release of TNF-ɑ (by 76%), IL-6 (by 68%), CCL2 (by 72%), and CCL3 (by 67%). In addition to antiviral activity, CQ may also mitigate the cytokine storm associated with severe pneumonia caused by coronaviruses. Grassin-Delyle et al., 5/8/2020, peer-reviewed, 8 authors.Share Tweet
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Carlucci et al., J. Med. Microbiol., Sep 15, 2020, doi: 10.1099/jmm.0.001250 (preprint 5/8) (Peer Reviewed) Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients Details Retrospective 932 patients. Addition of Zinc to HCQ+AZ reduces mortality / transfer to hospice, ICU admission, and the need for ventilation. Reduction in mortality or transfer to hospice adjusted odds ratio OR 0.56, _p_ = 0.002; increasei..
5/8 Details SourceLate treatment study Late treatment study Carlucci et al., J. Med. Microbiol., Sep 15, 2020, doi: 10.1099/jmm.0.001250 (preprint 5/8) (Peer Reviewed) Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients Retrospective 932 patients. Addition of Zinc to HCQ+AZ reduces mortality / transfer to hospice, ICU admission, and the need for
ventilation.
Reduction in mortality or transfer to hospice adjusted odds ratio OR 0.56, _p_ = 0.002; increase in being discharged home, adjusted OR1.53, _p_ = 0.008.
Carlucci et al., 5/8/2020, peer-reviewed, 6 authors.Share Tweet
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Konig et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-217690 (Letter) hosp., ↓3.0%, p=0.88 Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19 Details Analysis of 80 SLE patients diagnosed with COVID-19, showing the frequency of hospitalisation did not differ between individuals using an antimalarial versus non-users (55% (16/29) vs 57% (29/51), _p_=ns. Authors suggest that the dosage use.. 5/7 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Konig et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-217690 (Letter) Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19 Analysis of 80 SLE patients diagnosed with COVID-19, showing the frequency of hospitalisation did not differ between individuals using an antimalarial versus non-users (55% (16/29) vs 57% (29/51), _p_=ns. Authors suggest that the dosage used may be too low to reach
therapeutic levels.
risk of hospitalization, 3.0% lower, RR 0.97, _p_ = 0.88, treatment 16 of 29 (55.2%), control 29 of 51 (56.9%). Konig et al., 5/7/2020, retrospective, database analysis, multiple countries, multiple regions, preprint, 11 authors.Share Tweet
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Derendorf, H., Int. J. Antimicrobial Agents, 7 May 2020, doi:10.1016/j.ijantimicag.2020.106007 (Peer Reviewed) (Theory) (not included in the study count)theory
Excessive lysosomal ion-trapping of hydroxychloroquine andazithromycin
Details Discusses pharmacokinetic properties of HCQ+AZ as a potential underlying mechanism of the observedantiviral effects.
5/7 Details SourceTheory
Theory
Derendorf, H., Int. J. Antimicrobial Agents, 7 May 2020, doi:10.1016/j.ijantimicag.2020.106007 (Peer Reviewed) (Theory) (not included in the study count) Excessive lysosomal ion-trapping of hydroxychloroquine andazithromycin
Discusses pharmacokinetic properties of HCQ+AZ as a potential underlying mechanism of the observed antiviral effects. Derendorf et al., 5/7/2020, peer-reviewed, 1 author.Share Tweet
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Geleris et al., NEJM, May 7, 2020, doi:10.1056/NEJMoa2012410 (PeerReviewed)
int./death, ↑4.0%, p=0.76 Observational Study of Hydroxychloroquine in Hospitalized Patientswith Covid-19
Details There appears to be a major error in this paper. Before propensity matching, 38 control patients had hypertension. After propensity matching, 146 patients had hypertension (Table 1). This is not possible. Even if all propensity matched co.. 5/7 Details SourceLate treatment study Late treatment study Geleris et al., NEJM, May 7, 2020, doi:10.1056/NEJMoa2012410 (Peer
Reviewed)
Observational Study of Hydroxychloroquine in Hospitalized Patientswith Covid-19
There appears to be a major error in this paper. Before propensity matching, 38 control patients had hypertension. After propensity matching, 146 patients had hypertension (Table 1). This is not possible. Even if all propensity matched control patients had hypertension, the control prevalence would only be 14% compared to 49% for treatment. Since patients with hypertension are at much greater risk of mortality (HR 2.12, see ), this appears to invalidate theresults.
Observational study of 1,446 hospitalized patients showing no significant effect on a combined intubation/death outcome for latetreatment.
However, secondary analysis shows the success of HCQ was hidden by combining intubation and death - death / (combined death/intubation) for HCQ was 60% vs. control 89%, for details see: . RCT recommended. No AZ or Zinc. HCQ group much sicker - patients already in mild/moderate ARDS, most of the control group not in ARDS. Control cases received other therapeutics. academic.oup.com/eurheartj/article/41/22/2058/5851436 twitter.com/dperetti/status/1259154540630364162 risk of combined intubation/death, 4.0% higher, RR 1.04, _p_ = 0.76, treatment 262 of 811 (32.3%), control 84 of 565 (14.9%), adjusted. Geleris et al., 5/7/2020, retrospective, USA, North America, peer-reviewed, 12 authors.Share Tweet
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Sermo (News) (not included in the study count)news
Sermo reports: COVID-19 treatment trends over 6 weeks and 33,700 interviews: Usage, efficacy and safety perceptions of most-usedtherapies
Details HCQ used by 55% of physicians worldwide for COVID. Survey of 6,150 physicians. 5/7 Details SourceN/A
N/A
Sermo (News) (not included in the study count) Sermo reports: COVID-19 treatment trends over 6 weeks and 33,700 interviews: Usage, efficacy and safety perceptions of most-usedtherapies
HCQ used by 55% of physicians worldwide for COVID. Survey of 6,150physicians.
Sermo et al., 5/7/2020, preprint, 1 author.Share Tweet
Submit Corrections or Comments5/6 N/A
Maisonnasse et al., Nature, 2020, doi:10.1038/s41586-020-2558-4 (preprint 5/6) (Peer Reviewed) (not included in the study count)animal study
Hydroxychloroquine use against SARS-CoV-2 infection in non-humanprimates
Details Monkey study which reports no effect of HCQ or HCQ+AZ. However, there are several signs of effectiveness despite the very small sample sizes and 100% recovery of all treated and control monkeys. 58% reduction in lung lesions: thefinal d..
5/6 Details SourceN/A
N/A
Maisonnasse et al., Nature, 2020, doi:10.1038/s41586-020-2558-4 (preprint 5/6) (Peer Reviewed) (not included in the study count) Hydroxychloroquine use against SARS-CoV-2 infection in non-humanprimates
Monkey study which reports no effect of HCQ or HCQ+AZ. However, there are several signs of effectiveness despite the very small sample sizes and 100% recovery of all treated and control monkeys. 58% reduction in lung lesions: the final day lung lesion data shows 63% of control monkeys have lesions, while 26% of treated monkeys do, _p_=0.095 (the final day data is missing for 7 monkeys, these are predicted based on the day 5 results and the trend of comparablemonkeys).
97% increase in viral load recovery after one week: 3 of 8 control monkeys (38%) have recovered with <= 4 log10 copies/mL viral load, compared to 17 of 23 treated monkeys (74%), _p_=0.095. 3 of 8 (38%) control monkeys also have a higher peak viral load than 100% of the 23 treated monkeys post-treatment. The group with the lowest peak viral load is the PrEP group. All animals were infected with the same initial viral load, whereas real-world infections vary in the initial viral load, and lower inital viral loads allow greater time to mount an immune response. Severity of disease is not analyzed as compared to humans. The steep viral drops observed could also be related to immune system response. Maisonnasse et al., 5/6/2020, peer-reviewed, 24 authors.Share Tweet
Submit Corrections or Comments5/5 Late
Membrillo de Novales et al., Preprints 2020, 2020050057, doi:10.20944/preprints202005.0057.v1 (Preprint) death, ↓55.1%, p=0.002 Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study Details 166 patients hospitalised with COVID-19, HCQ increased survival 1.4 - 1.8 times when patients admitted in early stages. Early is relative to hospital admission here - all patients were in relatively serious condition. 5/5 Details SourceLate treatment study Late treatment study Membrillo de Novales et al., Preprints 2020, 2020050057, doi:10.20944/preprints202005.0057.v1 (Preprint) Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study 166 patients hospitalised with COVID-19, HCQ increased survival 1.4 - 1.8 times when patients admitted in early stages. Early is relative to hospital admission here - all patients were in relatively serious
condition.
risk of death, 55.1% lower, RR 0.45, _p_ = 0.002, treatment 27 of 123 (22.0%), control 21 of 43 (48.8%). Membrillo de Novales et al., 5/5/2020, retrospective, Spain, Europe, preprint, 19 authors.Share Tweet
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Million et al., Travel Med Infect Dis., 2020 May 5, doi:10.1016/j.tmaid.2020.101738 (Peer Reviewed) Early Treatment of COVID-19 Patients With Hydroxychloroquine and Azithromycin: A Retrospective Analysis of 1061 Cases in Marseille,France
Details Retrospective 1061 patients. HCQ+AZ safe and results in a low fatality rate. 5/5 Details SourceEarly, Late
Early, Late
Million et al., Travel Med Infect Dis., 2020 May 5, doi:10.1016/j.tmaid.2020.101738 (Peer Reviewed) Early Treatment of COVID-19 Patients With Hydroxychloroquine and Azithromycin: A Retrospective Analysis of 1061 Cases in Marseille,France
Retrospective 1061 patients. HCQ+AZ safe and results in a lowfatality rate.
Million et al., 5/5/2020, peer-reviewed, 37 authors.Share Tweet
Submit Corrections or Comments5/5 PrEP
Gendelman et al., Autoimmunity Reviews, 19:7, July 2020, doi:10.1016/j.autrev.2020.102566 (Peer Reviewed) cases, ↓8.1%, p=0.88 Continuous Hydroxychloroquine or Colchicine Therapy Does Not Prevent Infection With SARS-CoV-2: Insights From a Large HealthcareDatabase Analysis
Details Very small study of rheumatic disease/autoimmune disorder patients showing no significant difference but with only 3 chronic HCQ patient cases. Only considers people tested at a time when primarily symptomatic cases were tested. Otherr..
5/5 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Gendelman et al., Autoimmunity Reviews, 19:7, July 2020, doi:10.1016/j.autrev.2020.102566 (Peer Reviewed) Continuous Hydroxychloroquine or Colchicine Therapy Does Not Prevent Infection With SARS-CoV-2: Insights From a Large Healthcare
Database Analysis
Very small study of rheumatic disease/autoimmune disorder patients showing no significant difference but with only 3 chronic HCQ patient cases. Only considers people tested at a time when primarily symptomatic cases were tested. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, _p_<0.001 , which is the observed real-world risk, taking into account factors such as these patients potentially being more carefulto avoid exposure.
Adjusting for the difference in baseline risk using the result in Ferri et al. shows substantial benefit for HCQ, RR 0.211, but with only 3 HCQ cases the result is inconclusive. More recent studies with rheumatic disease/autoimmune condition patients provide higherconfidence.
c19study.com/ferri.html risk of COVID-19 case, 8.1% lower, RR 0.92, _p_ = 0.88, treatment 3 of 36 (8.3%), control 1314 of 14484 (9.1%). Gendelman et al., 5/5/2020, retrospective, database analysis, Israel, Middle East, peer-reviewed, 5 authors.Share Tweet
Submit Corrections or Comments5/5 PrEP
Mitchell et al., SSRN, doi:10.2139/ssrn.3586954 (Preprint) death, ↓99.0%, p<0.0001 Markedly Lower Rates of Coronavirus Infection and Fatality in Malaria-Endemic Regions – A Clue As to Treatment? Details Analysis of COVID-19 amongst 2.4B people shows a wide counterintuitive disparity between well-developed and less-developed countries, with more affluent countries about one hundred times more likely to be infected and die due to COVID-19... 5/5 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Mitchell et al., SSRN, doi:10.2139/ssrn.3586954 (Preprint) Markedly Lower Rates of Coronavirus Infection and Fatality in Malaria-Endemic Regions – A Clue As to Treatment? Analysis of COVID-19 amongst 2.4B people shows a wide counterintuitive disparity between well-developed and less-developed countries, with more affluent countries about one hundred times more likely to be infected and die due to COVID-19. They find the effect is most apparent when comparing to countries with the highest rates of endemic malaria. Since travelers to malaria-endemic countries are likely to be taking antimalarial prophylaxis and there is evidence of efficacy with COVID-19, authors find the data highly probative for the hypothesis that prophylactic antimalarial use by incoming visitors markedly attenuates a country’s COVID-19 fatality rate. While authors do not adjust for age differences, those adjustments can only account for a small fraction of the observed difference. risk of death, 99.0% lower, RR 0.01, _p_ < 0.001. Mitchell et al., 5/5/2020, retrospective, multiple countries, multiple regions, preprint, 2 authors.
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Submit Corrections or Comments5/4 PrEP
Huh et al., medRxiv, doi:10.1101/2020.05.04.20089904 (Preprint) cases, ↑47.7%, p=0.09 Association of previous medications with the risk of COVID-19: a nationwide claims-based study from South Korea Details Database analysis of many drugs and COVID-19 cases, with 23 cases taking HCQ, and 251 control patients not taking HCQ, showing OR 1.07, _p_=0.77, and in multivariable analysis OR 1.48, _p_=0.086. Patients taking HCQ are most likely taking it.. 5/4 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study Huh et al., medRxiv, doi:10.1101/2020.05.04.20089904 (Preprint) Association of previous medications with the risk of COVID-19: a nationwide claims-based study from South Korea Database analysis of many drugs and COVID-19 cases, with 23 cases taking HCQ, and 251 control patients not taking HCQ, showing OR 1.07, _p_=0.77, and in multivariable analysis OR 1.48, _p_=0.086. Patients taking HCQ are most likely taking it for systemic autoimmune diseases where the risk of COVID-19 is much higher, for example OR 4.42, _p_<0.001 according to (which includes factors such as systemic autoimmune disease patients potentially being more careful to avoid exposure). The result therefore suggests a substantial benefit for HCQ, as is also shown in Ferri et al. Adjusting for the difference in baseline risk of systemic autoimmune patients results in RR 0.24. Details of the multivarible analysis in the paper are not provided for assessment, but the analysis may be significantly affected by overfitting and/or multicollinearity. We note that many results in this study differ significantly from other research, for example proton pump inhibitors show OR 0.62, _p_<0.001 whereas PPIs are classified as "no expected benefit" and other research suggests they
increase risk.
c19study.com/ferri.html risk of COVID-19 case, 47.7% higher, RR 1.48, _p_ = 0.09, ORconverted to RR.
Huh et al., 5/4/2020, retrospective, case control, database analysis, South Korea, Asia, preprint, 10 authors.Share Tweet
Submit Corrections or Comments5/2 Late
Mallat et al., Medicine (Baltimore), doi:10.1097/MD.0000000000023720 (preprint 5/2) (Peer Reviewed) viral- time, ↑203.0%, p=0.02 Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease: Aretrospective study
Details Very small retrospective analysis of 34 patients finding slower binary PCR viral clearance with HCQ. No information on severity for treatment versus control is provided. No deaths, ICU admission, or mechanical ventilation. Binary PCR does.. 5/2 Details SourceLate treatment study Late treatment study Mallat et al., Medicine (Baltimore), doi:10.1097/MD.0000000000023720 (preprint 5/2) (Peer Reviewed) Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease: A
retrospective study
Very small retrospective analysis of 34 patients finding slower binary PCR viral clearance with HCQ. No information on severity for treatment versus control is provided. No deaths, ICU admission, or mechanical ventilation. Binary PCR does not distinguish replication-competence. HCQ treatment started very late for many patients with >= 9 days for 25%. time to viral-, 203.0% higher, relative time 3.03, _p_ = 0.02, treatment 23, control 11. Mallat et al., 5/2/2020, retrospective, Abu Dhabi, Middle East, peer-reviewed, 8 authors.Share Tweet
Submit Corrections or Comments5/1 N/A
Mercuro et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1834 (Peer Reviewed) (not included in thestudy count)
safety analysis
Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019(COVID-19)
Details Study of 90 hospitalized patients given HCQ, 53 also receiving AZ, 53% hypertension, 29% diabetes mellitus, baseline median QTc 473ms for HCQ, and 442ms for HCQ+AZ. Median change for HCQ+AZ ΔQTc of 23ms vs. 5.5ms for HCQ. Other factors su.. 5/1 Details SourceN/A
N/A
Mercuro et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1834 (Peer Reviewed) (not included in thestudy count)
Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019(COVID-19)
Study of 90 hospitalized patients given HCQ, 53 also receiving AZ, 53% hypertension, 29% diabetes mellitus, baseline median QTc 473ms for HCQ, and 442ms for HCQ+AZ. Median change for HCQ+AZ ΔQTc of 23ms vs. 5.5ms for HCQ. Other factors such as stress cardiomyopathy or myocarditis could not be ruled out. Without a control arm, they could not conclude that HCQ and AZ conferred increased cardiotoxic risk; however, compared with HCQ alone, ΔQTc differences were likely associated with the addition of AZ. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics or had a baseline QTc of 450 milliseconds or more. HCQ was discontinued in 10 patients due to adverse events including nausea, hypoglycemia, and 1 case of torsades de pointes. There were no deaths reported. Appropriate use and careful analysis of contraindications, risks, and benefits are important. More recent and much larger studies have not shown significant safety concerns, including outpatient RCTs showing no serious adverse events, and even the RECOVERY trial which used an unusually high dose of HCQ (including 237 patients also receiving AZ) reports they "did not show any excess in ventricular tachycardia (including torsade de pointes) or ventricular fibrillation in the hydroxychloroquine arm", and "serious cardiovascular toxicity has been reported very rarely despite the high prevalence of cardiovascular disease in hospitalized patients, the common occurrence of myocarditis in COVID-19, and the extensive use of hydroxychloroquine and azithromycin together." Mercuro et al., 5/1/2020, peer-reviewed, 7 authors.Share Tweet
Submit Corrections or Comments5/1 N/A
Bessière et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1787 (Peer Reviewed) (not included in thestudy count)
safety analysis
Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxychloroquine Alone or in Combination With Azithromycin in anIntensive Care Unit
Details Study of 40 very serious condition ICU patients, 75% required invasive mechanical ventilation, 63% received vasoactive drugs, 50% received other treatments favoring QT prolongation. HCQ with or w/o AZ was given to 45% and 55%respectively..
5/1 Details SourceN/A
N/A
Bessière et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1787 (Peer Reviewed) (not included in thestudy count)
Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxychloroquine Alone or in Combination With Azithromycin in anIntensive Care Unit
Study of 40 very serious condition ICU patients, 75% required invasive mechanical ventilation, 63% received vasoactive drugs, 50% received other treatments favoring QT prolongation. HCQ with or w/o AZ was given to 45% and 55% respectively. They showed an increase in QTc, more significant with the combination of HCQ+AZ where prolonged QTc was observed in 36% (10 with ΔQTc >60 milliseconds and 7 with QTc ≥500 milliseconds). No ventricular arrhythmia, including torsades de pointes, was recorded. While these results may not be generalizable outside the ICU, caution is recommended in use, especially with thecombination.
Appropriate use and careful analysis of contraindications, risks, and benefits are important. More recent and much larger studies have not shown significant safety concerns, including outpatient RCTs showing no serious adverse events, and even the RECOVERY trial which used an unusually high dose of HCQ (including 237 patients also receiving AZ) reports they "did not show any excess in ventricular tachycardia (including torsade de pointes) or ventricular fibrillation in the hydroxychloroquine arm", and "serious cardiovascular toxicity has been reported very rarely despite the high prevalence of cardiovascular disease in hospitalized patients, the common occurrence of myocarditis in COVID-19, and the extensive use of hydroxychloroquine and azithromycin together." Bessière et al., 5/1/2020, peer-reviewed, 7 authors.Share Tweet
Submit Corrections or Comments5/2 Late
Seydi (News) (not included in the study count)news
Coronavirus: a study in Senegal confirms the effectiveness ofhydroxychloroquine
Details Preliminary results of Senegal trial with 181 patients showing faster recovery with HCQ, and even faster recovery with HCQ+AZ. 5/2 Details SourceLate treatment study Late treatment study Seydi (News) (not included in the study count) Coronavirus: a study in Senegal confirms the effectiveness of
hydroxychloroquine
Preliminary results of Senegal trial with 181 patients showing faster recovery with HCQ, and even faster recovery with HCQ+AZ. Seydi et al., 5/2/2020, preprint, 1 author.Share Tweet
Submit Corrections or Comments4/30 Early
Meo et al., Eur. Rev. Med. Pharmacol. Sci. 2020, 24 (8), 4539-4547, doi:10.26355/eurrev_202004_21038 (Peer Reviewed) Efficacy of chloroquine and hydroxychloroquine in the treatment ofCOVID-19
Details Analysis of COVID-19 and malaria, finding that COVID-19 is highly pandemic in countries where malaria is least pandemic, and vice versa, suggesting that CQ/HCQ (widely used for malaria) are protective for COVID-19. This paper also include.. 4/30 Details SourceEarly treatment study Early treatment study Meo et al., Eur. Rev. Med. Pharmacol. Sci. 2020, 24 (8), 4539-4547, doi:10.26355/eurrev_202004_21038 (Peer Reviewed) Efficacy of chloroquine and hydroxychloroquine in the treatment of
COVID-19
Analysis of COVID-19 and malaria, finding that COVID-19 is highly pandemic in countries where malaria is least pandemic, and vice versa, suggesting that CQ/HCQ (widely used for malaria) are protective for COVID-19. This paper also includes a review of 9 articles supporting the efficacy of HCQ and CQ. Meo et al., 4/30/2020, peer-reviewed, 3 authors.Share Tweet
Submit Corrections or Comments4/27 Late
Sánchez-Álvarez et al., Nefrología, doi:10.1016/j.nefroe.2020.04.002 (Peer Reviewed) death, ↓45.9%, p=0.005 Status of SARS-CoV-2 infection in patients on renal replacement therapy. Report of the COVID-19 Registry of the Spanish Society ofNephrology (SEN)
Details Analysis of 868 patients on renal replacement therapy. Statistically significant reduction in mortality with HCQ for patients on dialysis (OR 0.47, _p_=0.005). No statistically significant change was found for transplant patients(the resu..
4/27 Details SourceLate treatment study Late treatment study Sánchez-Álvarez et al., Nefrología, doi:10.1016/j.nefroe.2020.04.002 (Peer Reviewed) Status of SARS-CoV-2 infection in patients on renal replacement therapy. Report of the COVID-19 Registry of the Spanish Society of
Nephrology (SEN)
Analysis of 868 patients on renal replacement therapy. Statistically significant reduction in mortality with HCQ for patients on dialysis (OR 0.47, _p_=0.005). No statistically significant change was found for transplant patients (the result is not given but likely the sample size is too small - the number of transplant patients was half the number of dialysispatients).
risk of death, 45.9% lower, RR 0.54, _p_ = 0.005, treatment 322, control 53, OR converted to RR. Sánchez-Álvarez et al., 4/27/2020, retrospective, database analysis, Spain, Europe, peer-reviewed, mean age 67.0, 10 authors.Share Tweet
Submit Corrections or Comments4/29 N/A
Saleh et al., Circulation: Arrhythmia and Electrophysiology, doi:10.1161/CIRCEP.120.008662 (Peer Reviewed)safety analysis
The Effect of Chloroquine, Hydroxychloroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection Details 201 hospitalized patients. No serious side effects of HCQ. No instances of Torsade de pointes, or arrhythmogenic death were reported. They report that although use of these medications resulted in QT prolongation, clinicians seldom needt..
4/29 Details SourceN/A
N/A
Saleh et al., Circulation: Arrhythmia and Electrophysiology, doi:10.1161/CIRCEP.120.008662 (Peer Reviewed) The Effect of Chloroquine, Hydroxychloroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection 201 hospitalized patients. No serious side effects of HCQ. No instances of Torsade de pointes, or arrhythmogenic death were reported. They report that although use of these medications resulted in QT prolongation, clinicians seldom need to discontinue therapy. Saleh et al., 4/29/2020, peer-reviewed, 17 authors.Share Tweet
Submit Corrections or Comments4/27 N/A
Klimke et al., Med. Hypotheses, doi:10.1016/j.mehy.2020.109783(Peer Reviewed)
dosing study
Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection Details Proposal to use HCQ as an aerosol in order to reach sufficient therapeutic levels at the alveolar epithelial cells. Authors suggest this will reduce adverse drug reactions compared with oral application, and the increase intolerability e..
4/27 Details SourceN/A
N/A
Klimke et al., Med. Hypotheses, doi:10.1016/j.mehy.2020.109783(Peer Reviewed)
Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection Proposal to use HCQ as an aerosol in order to reach sufficient therapeutic levels at the alveolar epithelial cells. Authors suggest this will reduce adverse drug reactions compared with oral application, and the increase in tolerability enables a broader use for prevention and post-exposure prophylaxis, which would be an advantage especially for high-risk, multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application is presented, showing inhalation was well tolerated. Klimke et al., 4/27/2020, peer-reviewed, 4 authors.Share Tweet
Submit Corrections or Comments4/26 Late
Auld et al., Critical Care Medicine, doi:10.1097/ccm.0000000000004457 (Peer Reviewed) death, ↑2.8%, p=1.00 ICU and ventilator mortality among critically ill adults withCOVID-19
Details Retrospective 217 critically ill patients, 114 receiving HCQ, showing no significant difference in mortality. 4/26 Details SourceLate treatment study Late treatment study Auld et al., Critical Care Medicine, doi:10.1097/ccm.0000000000004457 (Peer Reviewed) ICU and ventilator mortality among critically ill adults with
COVID-19
Retrospective 217 critically ill patients, 114 receiving HCQ, showing no significant difference in mortality. risk of death, 2.8% higher, RR 1.03, _p_ = 1.00, treatment 33 of 114 (28.9%), control 29 of 103 (28.2%). Auld et al., 4/26/2020, retrospective, USA, North America, peer-reviewed, 14 authors.Share Tweet
Submit Corrections or Comments4/25 In Vitro
Andreani et al., Microbial Pathogenesis, doi:/10.1016/j.micpath.2020.104228 (Peer Reviewed) (In Vitro) (not included in the study count)_in vitro_
In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect Details HCQ and AZ has a synergistic effect _in vitro_ on SARS-CoV-2 at concentrations compatible with that obtained in human lung. 4/25 Details SourceIn Vitro
In Vitro
Andreani et al., Microbial Pathogenesis, doi:/10.1016/j.micpath.2020.104228 (Peer Reviewed) (In Vitro) (not included in the study count) In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect HCQ and AZ has a synergistic effect _in vitro_ on SARS-CoV-2 at concentrations compatible with that obtained in human lung. Andreani et al., 4/25/2020, peer-reviewed, 11 authors.Share Tweet
Submit Corrections or Comments4/24 Early
Ashraf et al., medRxiv doi:10.1101/2020.04.20.20072421.t(Preprint)
death, ↓67.5%, p=0.15 COVID-19 in Iran, a comprehensive investigation from exposure totreatment outcomes
Details Small limited trial with 100 patients concluding that HCQ improved clinical outcome, OR 0.016 in regression analysis. 4/24 Details SourceEarly treatment study Early treatment study Ashraf et al., medRxiv doi:10.1101/2020.04.20.20072421.t (Preprint) COVID-19 in Iran, a comprehensive investigation from exposure to
treatment outcomes
Small limited trial with 100 patients concluding that HCQ improved clinical outcome, OR 0.016 in regression analysis. risk of death, 67.5% lower, RR 0.32, _p_ = 0.15, treatment 10 of 77 (13.0%), control 2 of 5 (40.0%). Ashraf et al., 4/24/2020, retrospective, database analysis, Iran, Middle East, preprint, median age 58.0, 16 authors, dosage 200mg bid daily, 400mg qd was used when combined with Lopinavir-Ritonavir.Share Tweet
Submit Corrections or Comments4/21 Late
Izoulet M., SSRN, doi:10.2139/ssrn.3575899 (Preprint) death, ↓85.0%, p<0.001 Countries which Primarily Use Antimalarial Drugs As COVID-19 Treatment See Slower Dynamic of Daily Deaths Details Compares the dynamics of daily deaths in the 10 days following the 3rd death in countries using and not using CQ, showing dramatically lower death in CQ countries. This paper does not attempt to account for population age and other .. 4/21 Details SourceLate treatment study Late treatment study Izoulet M., SSRN, doi:10.2139/ssrn.3575899 (Preprint) Countries which Primarily Use Antimalarial Drugs As COVID-19 Treatment See Slower Dynamic of Daily Deaths Compares the dynamics of daily deaths in the 10 days following the 3rd death in countries using and not using CQ, showing dramatically lower death in CQ countries. This paper does not attempt to account for population age and other differences between the countries and recommends further study. risk of death, 85.0% lower, RR 0.15, _p_ < 0.001. Izoulet et al., 4/21/2020, retrospective, multiple countries, multiple regions, preprint, 1 author, dosage not specified.
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Submit Corrections or Comments4/21 Late
Magagnoli et al., Med (2020), doi:10.1016/j.medj.2020.06.001 (preprint 4/21) (Peer Reviewed) death, ↓11.0%, p=0.74 Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19 Details Retrospective 807 hospitalized patients, no statistically significant reduction in mortality or the need for mechanical ventilation with HCQ or HCQ+AZ, or for death with HCQ+AZ, HR 1.83, _p_=0.009 for HCQ mortality. The preprint notes tha.. 4/21 Details SourceLate treatment study Late treatment study Magagnoli et al., Med (2020), doi:10.1016/j.medj.2020.06.001 (preprint 4/21) (Peer Reviewed) Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19 Retrospective 807 hospitalized patients, no statistically significant reduction in mortality or the need for mechanical ventilation with HCQ or HCQ+AZ, or for death with HCQ+AZ, HR 1.83, _p_=0.009 for HCQ
mortality.
The preprint notes that HCQ was more likely to be prescribed to patients with more severe disease, however this was deleted in thepublished version.
425 patients had dispositions of death or discharge by the end of the study period and thus did not encounter the issue of length-biased sampling and differential rates of right-censored observations amongthe groups.
Also see:
mediterranee-infection.com/wp-content/uploads/2020/04/Response-to-Magagnoli.pdf risk of death, 11.0% lower, RR 0.89, _p_ = 0.74, treatment 39 of 148 (26.4%), control 18 of 163 (11.0%), adjusted, HCQ+AZ w/dispositions. risk of death, 1.0% lower, RR 0.99, _p_ = 0.98, treatment 30 of 114 (26.3%), control 18 of 163 (11.0%), adjusted, HCQ w/dispositions. risk of death, 31.0% higher, RR 1.31, _p_ = 0.28, treatment 49 of 214 (22.9%), control 37 of 395 (9.4%), adjusted, HCQ+AZ. risk of death, 83.0% higher, RR 1.83, _p_ = 0.009, treatment 38 of 198 (19.2%), control 37 of 395 (9.4%), adjusted, HCQ. Magagnoli et al., 4/21/2020, retrospective, database analysis, USA, North America, peer-reviewed, 7 authors.Share Tweet
Submit Corrections or Comments4/17 PEP
Lee at al., Int. J. Antimicrob. Agents, 2020, Apr 17, doi:10.1016/j.ijantimicag.2020.105988 (Peer Reviewed) Can Post-Exposure Prophylaxis for COVID-19 Be Considered as an Outbreak Response Strategy in Long-Term Care Hospitals? Details Post exposure prophylaxis of 211 high-risk people after major exposure event in a long term care hospital, showing no positive cases after 14 days. 4/17 Details SourcePost Exposure Prophylaxis study Post Exposure Prophylaxis study Lee at al., Int. J. Antimicrob. Agents, 2020, Apr 17, doi:10.1016/j.ijantimicag.2020.105988 (Peer Reviewed) Can Post-Exposure Prophylaxis for COVID-19 Be Considered as an Outbreak Response Strategy in Long-Term Care Hospitals? Post exposure prophylaxis of 211 high-risk people after major exposure event in a long term care hospital, showing no positive cases
after 14 days.
Lee et al., 4/17/2020, peer-reviewed, 3 authors.Share Tweet
Submit Corrections or Comments4/16 Late
Borba et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2020.8857 (Peer Reviewed) Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study) Details Comparison of typical CQ dosage with high dosage CQ (600mg CQ twice daily for 10 days), showing higher mortality with high dosage, OR 2.8 when controlled by age in multivariate analysis. Increased incidence of prolonged QT an.. 4/16 Details SourceLate treatment study Late treatment study Borba et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2020.8857 (Peer Reviewed) Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study) Comparison of typical CQ dosage with high dosage CQ (600mg CQ twice daily for 10 days), showing higher mortality with high dosage, OR 2.8 when controlled by age in multivariate analysis. Increased incidence of prolonged QT and death in high dose treatment arm. Patients >75 only enrolled in high dose arm, age of high dose arm significantly higher than low dose arm (_p_=0.02). Very sick at baseline, 46% in ICU, 89% on oxygen therapy (this information can be found in the preprint ). medrxiv.org/content/10.1101/2020.04.07.20056424v2 Borba et al., 4/16/2020, peer-reviewed, mean age 51.1, 28 authors.
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Submit Corrections or Comments4/15 Early, Late
Esper et al., Prevent Senior Institute, São Paulo, Brazil(Preprint)
hosp., ↓64.0%, p=0.02 Empirical treatment with hydroxychloroquine and azithromycin for suspected cases of COVID-19 followed-up by telemedicine Details 636 patients. HCQ+AZ reduced hospitalization 79% when used within 7 days (65% overall).Non-randomized.
4/15 Details SourceEarly, Late
Early, Late
Esper et al., Prevent Senior Institute, São Paulo, Brazil(Preprint)
Empirical treatment with hydroxychloroquine and azithromycin for suspected cases of COVID-19 followed-up by telemedicine 636 patients. HCQ+AZ reduced hospitalization 79% when used within 7 days (65% overall). Non-randomized. risk of hospitalization, 64.0% lower, RR 0.36, _p_ = 0.02, treatment 8 of 412 (1.9%), control 12 of 224 (5.4%). Esper et al., 4/15/2020, prospective, Brazil, South America, preprint, 15 authors, dosage 800mg day 1, 400mg days 2-7.Share Tweet
Submit Corrections or Comments4/15 Theory
Brufsky, A., J. Medical Virology, doi:10.1002/jmv.25887 (Peer Reviewed) (Theory) (not included in the study count)theory
Hyperglycemia, hydroxychloroquine, and the COVID‐19 pandemic Details Theory on the effectiveness of HCQ. HCQ has been shown to block the polarization of macrophages to an M1 inflammatory subtype and is predicted to interfere with glycosylation of a number of proteins involved in the humoral immune response.. 4/15 Details SourceTheory
Theory
Brufsky, A., J. Medical Virology, doi:10.1002/jmv.25887 (Peer Reviewed) (Theory) (not included in the study count) Hyperglycemia, hydroxychloroquine, and the COVID‐19 pandemic Theory on the effectiveness of HCQ. HCQ has been shown to block the polarization of macrophages to an M1 inflammatory subtype and is predicted to interfere with glycosylation of a number of proteins involved in the humoral immune response, possibly including the macrophage FcR gamma IgG receptor and other immunomodulatory proteins, potentially through inhibition of UDP‐N‐acetylglucosamine 2‐epimerase. In combination with potential other immunomodulatory effects, this could possibly blunt the progression of COVID‐19 pneumonia all to way up to ARDS. Brufsky et al., 4/15/2020, peer-reviewed, 1 author.Share Tweet
Submit Corrections or Comments4/14 Late
Tang et al., BMJ 2020, 369, doi:10.1136/bmj.m1849 (Peer Reviewed) viral+, ↓21.4%, p=0.51 Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial Details 150 patients very late stage RCT showing no significant difference. Treatment very late, average 16.6 days after symptom onset. Data favorable to HCQ was deleted in the second version, see analysis . " accelerate the all.. 4/14 Details SourceLate treatment study Late treatment study Tang et al., BMJ 2020, 369, doi:10.1136/bmj.m1849 (Peer Reviewed) Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial 150 patients very late stage RCT showing no significant difference. Treatment very late, average 16.6 days after symptom onset. Data favorable to HCQ was deleted in the second version, see analysis . " accelerate the alleviation of clinical symptoms"; "More rapid alleviation of clinical symptoms with SOC plus HCQ than with SOC alone was observed during the second week since randomization"; "The efficacy of HCQ on the alleviation of symptoms, HR 8.83 , was more evident when the confounding effects of other anti-viral agents were removed" mediterranee-infection.com/tang-et-al-bmj-donnees-favorables-a-lhydroxychloroquine-supprimees/ risk of no virological cure at day 21, 21.4% lower, RR 0.79, _p_ = 0.51, treatment 11 of 75 (14.7%), control 14 of 75 (18.7%). Tang et al., 4/14/2020, Randomized Controlled Trial, China, Asia, peer-reviewed, 24 authors.
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Submit Corrections or Comments4/13 Late
Gao et al., Biosci Trends, May 21, 2020, 14:2, 156-158, doi:10.5582/bst.2020.03072, Epub Apr 13, 2020 (Review) (Peer Reviewed) (not included in the study count)review
Update on Use of Chloroquine/Hydroxychloroquine to Treat Coronavirus Disease 2019 (COVID-19) Details Increasing evidence from completed clinical studies shows CQ and HCQ effective (HCQ more effective). 4/13 Details SourceLate treatment study Late treatment study Gao et al., Biosci Trends, May 21, 2020, 14:2, 156-158, doi:10.5582/bst.2020.03072, Epub Apr 13, 2020 (Review) (Peer Reviewed) (not included in the study count) Update on Use of Chloroquine/Hydroxychloroquine to Treat Coronavirus Disease 2019 (COVID-19) Increasing evidence from completed clinical studies shows CQ and HCQ effective (HCQ more effective). Gao et al., 4/13/2020, peer-reviewed, 2 authors.
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Submit Corrections or Comments4/12 Late
Barbosa et al., Preprint (Preprint) death, ↑147.0%, p=0.58 Clinical outcomes of hydroxychloroquine in hospitalized patients with COVID-19: a quasi-randomized comparative study Details Small retrospective study with 63 patients (32 treated with HCQ), showing no effectiveness, however the baseline state of each arm significantly differs. This preprint was submitted to NEJM but has not been published several months later. 4/12 Details SourceLate treatment study Late treatment study Barbosa et al., Preprint (Preprint) Clinical outcomes of hydroxychloroquine in hospitalized patients with COVID-19: a quasi-randomized comparative study Small retrospective study with 63 patients (32 treated with HCQ), showing no effectiveness, however the baseline state of each arm significantly differs. This preprint was submitted to NEJM but has not been published several
months later.
risk of death, 147.0% higher, RR 2.47, _p_ = 0.58, treatment 2 of 17 (11.8%), control 1 of 21 (4.8%). Barbosa et al., 4/12/2020, retrospective, USA, North America, preprint, 5 authors.Share Tweet
Submit Corrections or Comments4/11 Early
Gautret et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101663 (Peer Reviewed) Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study Details Pilot study suggesting improvement with HCQ+AZ and recommending further study. 80 patients with relatively mild cases, no control group, and no attempt to analyze confounding factors. 4/11 Details SourceEarly treatment study Early treatment study Gautret et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101663 (Peer Reviewed) Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study Pilot study suggesting improvement with HCQ+AZ and recommending further study. 80 patients with relatively mild cases, no control group, and no attempt to analyze confounding factors. Gautret et al., 4/11/2020, peer-reviewed, 29 authors.
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Submit Corrections or Comments4/10 Late
Lover, medRxiv, doi:10.1101/2020.03.22.20040949 (Preprint) (meta analysis - not included in study count)meta-analysis
Quantifying treatment effects of hydroxychloroquine and azithromycin for COVID-19: a secondary analysis of an open label non-randomized clinical trial (Gautret et al, 2020) Details Secondary analysis of Gautret et al. showing "modest to no impact of HCQ treatment, with more significanteffects from ".
4/10 Details SourceLate treatment study Late treatment study Lover, medRxiv, doi:10.1101/2020.03.22.20040949 (Preprint) (meta analysis - not included in study count) Quantifying treatment effects of hydroxychloroquine and azithromycin for COVID-19: a secondary analysis of an open label non-randomized clinical trial (Gautret et al, 2020) Secondary analysis of Gautret et al. showing "modest to no impact of HCQ treatment, with more significant effects from ". Lover et al., 4/10/2020, preprint, 1 author.
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Submit Corrections or Comments4/3 Theory
Fantini et al., Int J Antimicrob Agents, 55:5, doi:10.1016/j.ijantimicag.2020.105960 (Peer Reviewed) (Theory) (not included in the study count)theory
Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2infection
Details In-silico analysis confirming the antiviral properties of CQ, showing a new mechanism of action of CQ, and showing that HCQ is more potent than CQ. 4/3 Details SourceTheory
Theory
Fantini et al., Int J Antimicrob Agents, 55:5, doi:10.1016/j.ijantimicag.2020.105960 (Peer Reviewed) (Theory) (not included in the study count) Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2infection
In-silico analysis confirming the antiviral properties of CQ, showing a new mechanism of action of CQ, and showing that HCQ is more potentthan CQ.
Fantini et al., 4/3/2020, peer-reviewed, 4 authors.Share Tweet
Submit Corrections or Comments4/1 Early
Huang et al., Journal of Molecular Cell Biology, Volume 12, Issue 4, April 2020, 322–325, doi:10.1093/jmcb/mjaa014 (Peer Reviewed) no recov., ↓91.7%, p=0.02 Treating COVID-19 with Chloroquine Details 22 patients. All CQ patients discharged by day 14 versus 50% of Lopinavir/Rotinavir patients. Symptom onset to treatment 2.5 days for CQ vs. 6.5 days for Lopinavir/Rotinavir. 4/1 Details SourceEarly treatment study Early treatment study Huang et al., Journal of Molecular Cell Biology, Volume 12, Issue 4, April 2020, 322–325, doi:10.1093/jmcb/mjaa014 (Peer Reviewed) Treating COVID-19 with Chloroquine 22 patients. All CQ patients discharged by day 14 versus 50% of Lopinavir/Rotinavir patients. Symptom onset to treatment 2.5 days for CQ vs. 6.5 days for Lopinavir/Rotinavir. risk of no recovery at day 14, 91.7% lower, RR 0.08, _p_ = 0.02, treatment 0 of 10 (0.0%), control 6 of 12 (50.0%), continuity correction due to zero event. risk of no improvement in pneumonia at day 14, 83.0% lower, RR 0.17, _p_ = 0.22, treatment 10, control 12. Huang et al., 4/1/2020, Randomized Controlled Trial, China, Asia, peer-reviewed, 18 authors, dosage chloroquine 500mg bid days 1-10.
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Submit Corrections or Comments3/31 Late
Chen et al., medRxiv doi:10.1101/2020.03.22.20040758 (Preprint) pneumonia, ↓57.0%, p=0.04 Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial Details 62 patients. RCT showing significantly faster recovery with HCQ. 13% progressed to severe cases in the control group, versus 0% for the treatment group. Significant improvement seen in pneumonia on chest CT for 61% of treated patientsand..
3/31 Details SourceLate treatment study Late treatment study Chen et al., medRxiv doi:10.1101/2020.03.22.20040758 (Preprint) Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial 62 patients. RCT showing significantly faster recovery with HCQ. 13% progressed to severe cases in the control group, versus 0% for the treatment group. Significant improvement seen in pneumonia on chest CT for 61% of treated patients and 16% of control patients. risk of no improvement in pneumonia at day 6, 57.0% lower, RR 0.43, _p_ = 0.04, treatment 6 of 31 (19.4%), control 14 of 31 (45.2%). Chen et al., 3/31/2020, Randomized Controlled Trial, China, Asia, preprint, 9 authors.
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Submit Corrections or Comments3/31 In Vitro
Clementi et al., Front. Microbiol., 10 July 2020, doi:10.3389/fmicb.2020.01704 (preprint 3/31) (Peer Reviewed) (In Vitro) (not included in the study count)_in vitro_
Combined Prophylactic and Therapeutic Use Maximizes Hydroxychloroquine Anti-SARS-CoV-2 Effects in vitro Details _In vitro_ study, not included in the study count or percentages, showing greater inhibition for combined pre and post-exposure treatment for Vero E6 and Caco-2 cells. 3/31 Details SourceIn Vitro
In Vitro
Clementi et al., Front. Microbiol., 10 July 2020, doi:10.3389/fmicb.2020.01704 (preprint 3/31) (Peer Reviewed) (In Vitro) (not included in the study count) Combined Prophylactic and Therapeutic Use Maximizes Hydroxychloroquine Anti-SARS-CoV-2 Effects in vitro _In vitro_ study, not included in the study count or percentages, showing greater inhibition for combined pre and post-exposure treatment for Vero E6 and Caco-2 cells. Clementi et al., 3/31/2020, peer-reviewed, 10 authors.Share Tweet
Submit Corrections or Comments3/28 Late
Molina et al., Médecine et Maladies Infectieuses, 50:4, June 2020, 10.1016/j.medmal.2020.03.006 (preprint 3/28) (Letter) No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection Details Report on 11 patients treated with HCQ with no control group. Authors suggest there is no evidence of benefit for HCQ based on PCR+ results for 8/10 patients at day 5-6. Binary PCR evaluation with an unknown Ct. Binary PCR does not distin.. 3/28 Details SourceLate treatment study Late treatment study Molina et al., Médecine et Maladies Infectieuses, 50:4, June 2020, 10.1016/j.medmal.2020.03.006 (preprint 3/28) (Letter) No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection Report on 11 patients treated with HCQ with no control group. Authors suggest there is no evidence of benefit for HCQ based on PCR+ results for 8/10 patients at day 5-6. Binary PCR evaluation with an unknown Ct. Binary PCR does not distinguish replication-competence. Molina et al., 3/28/2020, preprint, 7 authors.
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Submit Corrections or Comments3/26 Late
Zhong Nanshan (钟南山) (Preprint) viral+, ↓80.0%, p<0.0001 Efficacy and safety of chloroquine for treatment of COVID-19. An open-label, multi-center, non-randomized trial Details 197 patients. CQ effective. Day 10 viral RNA negative 91.4% HCQ versus 57.4% control. Median time to negative test 3 days versus 9 days for control. 3/26 Details SourceLate treatment study Late treatment study Zhong Nanshan (钟南山) (Preprint) Efficacy and safety of chloroquine for treatment of COVID-19. An open-label, multi-center, non-randomized trial 197 patients. CQ effective. Day 10 viral RNA negative 91.4% HCQ versus 57.4% control. Median time to negative test 3 days versus 9
days for control.
risk of no virological cure at day 10, 80.0% lower, RR 0.20, _p_ < 0.001, treatment 5 of 115 (4.3%), control 17 of 82 (20.7%), adjusted. Zhong et al., 3/26/2020, retrospective, China, Asia, preprint, 1author.
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Submit Corrections or Comments3/24 Theory
Pagliano et al., Clin. Infect. Dis., 2020 Mar 24, doi:10.1093/cid/ciaa320 (Peer Reviewed) (Theory) (not included in thestudy count)
theory
Is Hydroxychloroquine a Possible Post-Exposure Prophylaxis Drug to Limit the Transmission to Health Care Workers Exposed to COVID19? Details CQ and HCQ inhibit replication at early stages of infection, no similar effect reported for other drugs which are only able to interfere after cell infection. Large volume of existing data on safety. (8/23: we corrected the classification.. 3/24 Details SourceTheory
Theory
Pagliano et al., Clin. Infect. Dis., 2020 Mar 24, doi:10.1093/cid/ciaa320 (Peer Reviewed) (Theory) (not included in thestudy count)
Is Hydroxychloroquine a Possible Post-Exposure Prophylaxis Drug to Limit the Transmission to Health Care Workers Exposed to COVID19? CQ and HCQ inhibit replication at early stages of infection, no similar effect reported for other drugs which are only able to interfere after cell infection. Large volume of existing data on safety. (8/23: we corrected the classification of this study) Pagliano et al., 3/24/2020, peer-reviewed, 5 authors.Share Tweet
Submit Corrections or Comments3/23 Theory
Hu et al., Nature Nanotechnology, 15, 247–249, 2020, doi:10.1038/s41565-020-0674-9 (Peer Reviewed) (Theory) (not includedin the study count)
theory
Insights from nanomedicine into chloroquine efficacy againstCOVID-19
Details CQ is known in nanomedicine research for the investigation of nanoparticle uptake in cells, and may have potential for the treatment of COVID-19. 3/23 Details SourceTheory
Theory
Hu et al., Nature Nanotechnology, 15, 247–249, 2020, doi:10.1038/s41565-020-0674-9 (Peer Reviewed) (Theory) (not includedin the study count)
Insights from nanomedicine into chloroquine efficacy againstCOVID-19
CQ is known in nanomedicine research for the investigation of nanoparticle uptake in cells, and may have potential for the treatmentof COVID-19.
Hu et al., 3/23/2020, peer-reviewed, 3 authors.Share Tweet
Submit Corrections or Comments3/21 PrEP
ICMR, Indian Council of Medical Research (Advisory) (not includedin the study count)
advisory
Advisory on the use of hydroxy-chloroquine as prophylaxis for SARS-CoV-2 infection Details Recommends HCQ for prophylaxis in asymptomatic healthcare workers as found effective in-vitro andin-vivo.
3/21 Details SourcePre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study ICMR, Indian Council of Medical Research (Advisory) (not included
in the study count)
Advisory on the use of hydroxy-chloroquine as prophylaxis for SARS-CoV-2 infection Recommends HCQ for prophylaxis in asymptomatic healthcare workers as found effective in-vitro and in-vivo. ICMR et al., 3/21/2020, preprint, 1 author.Share Tweet
Submit Corrections or Comments3/20 Late
Hu et al., Shanghai Combined Task Force on COVID-19 (News) (not included in the study count)news
Shanghai Experience of COVID-19 Management Details Clinical studies of HCQ with 184 cases and 21 hospitals show HCQ is effective. 3/20 Details SourceLate treatment study Late treatment study Hu et al., Shanghai Combined Task Force on COVID-19 (News) (not included in the study count) Shanghai Experience of COVID-19 Management Clinical studies of HCQ with 184 cases and 21 hospitals show HCQ is
effective.
Hu et al., 3/20/2020, preprint, 1 author.Share Tweet
Submit Corrections or Comments3/18 In Vitro
Liu et al., Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0 (Peer Reviewed) (In Vitro) (not includedin the study count)
_in vitro_
Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro Details HCQ effective _in vitro_ and less toxic than CQ. In addition to direct antiviral activity, HCQ is a safe and successful anti-inflammatory agent that has been used extensively in autoimmune diseases and can significantly decrease the product.. 3/18 Details SourceIn Vitro
In Vitro
Liu et al., Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0 (Peer Reviewed) (In Vitro) (not includedin the study count)
Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro HCQ effective _in vitro_ and less toxic than CQ. In addition to direct antiviral activity, HCQ is a safe and successful anti-inflammatory agent that has been used extensively in autoimmune diseases and can significantly decrease the production of cytokines and, in particular, pro-inflammatory factors. Therefore, in COVID-19 patients, HCQ may also contribute to attenuating the inflammatory response. Careful design of clinical trials is important to achieve efficient and safe control of the infection. Liu et al., 3/18/2020, peer-reviewed, 10 authors.Share Tweet
Submit Corrections or Comments3/17 Early
Gautret et al., Int. J. of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.105949 (preprint 3/17) (Peer Reviewed) viral+, ↓66.0%, p=0.001 Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial Details HCQ was significantly associated with reduction / elimination of viral load, which was enhanced with AZ. Updated 8/13: responses to this paper have raised methodological issues . Despite the limitations, this early observational.. 3/17 Details SourceEarly treatment study Early treatment study Gautret et al., Int. J. of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.105949 (preprint 3/17) (Peer Reviewed) Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial HCQ was significantly associated with reduction / elimination of viral load, which was enhanced with AZ. Updated 8/13: responses to this paper have raised methodological issues . Despite the limitations, this early observational study was a milestone in the discovery process, including detailed daily evolution of PCR positivity. This study should be viewed in the context of the series of studies from this group. An update to this paper, including originally excluded patients, confirms the effectiveness of HCQ+AZ on viral clearance and early
discharge .
Also see
and the response from the authors . sciencedirect.com/science/article/pii/S092485792030251X sciencedirect.com/science/article/pii/S0924857920302338 sciencedirect.com/science/article/pii/S0924857920302260 sciencedirect.com/science/article/abs/pii/S0924857920300996 sciencedirect.com/science/article/pii/S0924857921000224 sciencedirect.com/science/article/pii/S0924857921000364 risk of no virological cure at day 6, 66.0% lower, RR 0.34, _p_ = 0.001, treatment 6 of 20 (30.0%), control 14 of 16 (87.5%). Gautret et al., 3/17/2020, prospective, France, Europe, peer-reviewed, 18 authors, dosage 200mg tid days 1-10.Share Tweet
Submit Corrections or Comments3/17 N/A
Sahraei et al., Int. J. Antimicrobial Agents, April 2020, 55:4, doi:10.1016/j.ijantimicag.2020.105945 (Review) (Peer Reviewed) (not included in the study count)review
Aminoquinolines against coronavirus disease 2019 (COVID-19): chloroquine or hydroxychloroquine Details Discussion of mechanisms of action, CQ vs. HCQ, early studies, safety. 3/17 Details SourceN/A
N/A
Sahraei et al., Int. J. Antimicrobial Agents, April 2020, 55:4, doi:10.1016/j.ijantimicag.2020.105945 (Review) (Peer Reviewed) (not included in the study count) Aminoquinolines against coronavirus disease 2019 (COVID-19): chloroquine or hydroxychloroquine Discussion of mechanisms of action, CQ vs. HCQ, early studies,safety.
Sahraei et al., 3/17/2020, peer-reviewed, 4 authors.Share Tweet
Submit Corrections or Comments3/13 N/A
Todaro and Rigano (Review) (Preprint) (not included in the studycount)
review
An Effective Treatment for Coronavirus (COVID-19) Details Discussion of existing research, treatment guidelines, and mechanisms of action for CQ and HCQ,recommending use.
3/13 Details SourceN/A
N/A
Todaro and Rigano (Review) (Preprint) (not included in the studycount)
An Effective Treatment for Coronavirus (COVID-19) Discussion of existing research, treatment guidelines, and mechanisms of action for CQ and HCQ, recommending use. Todaro et al., 3/13/2020, preprint, 2 authors.Share Tweet
Submit Corrections or Comments3/12 Theory
Devaux et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.105938 (Peer Reviewed) (Theory) (not included in the study count)theory
New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Details Discusses mechanisms of CQ interference with the SARS-CoV-2 replication cycle. 3/12 Details SourceTheory
Theory
Devaux et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.105938 (Peer Reviewed) (Theory) (not included in the study count) New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Discusses mechanisms of CQ interference with the SARS-CoV-2replication cycle.
Devaux et al., 3/12/2020, peer-reviewed, 4 authors.Share Tweet
Submit Corrections or Comments3/10 N/A
Cortegiani et al., J. Crit. Care, June 2020, 57:279-283, doi:10.1016/j.jcrc.2020.03.005, Epub Mar 10, 2020 (Peer Reviewed) (meta analysis - not included in study count)meta-analysis
A Systematic Review on the Efficacy and Safety of Chloroquine for the Treatment of COVID-19 Details Review of six articles and 23 ongoing clinical trials in China recommending research and clinical use adhering to MEURI. 3/10 Details SourceN/A
N/A
Cortegiani et al., J. Crit. Care, June 2020, 57:279-283, doi:10.1016/j.jcrc.2020.03.005, Epub Mar 10, 2020 (Peer Reviewed) (meta analysis - not included in study count) A Systematic Review on the Efficacy and Safety of Chloroquine for the Treatment of COVID-19 Review of six articles and 23 ongoing clinical trials in China recommending research and clinical use adhering to MEURI. Cortegiani et al., 3/10/2020, peer-reviewed, 5 authors.Share Tweet
Submit Corrections or Comments3/9 In Vitro
Yao et al., Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237 (Peer Reviewed) (In Vitro) (not included inthe study count)
_in vitro_
In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Details HCQ is more potent than CQ _in vitro_ for inhibiting SARS-CoV-2. Simulates HCQ concentration in lung fluid and provides dosing recommendations. See also . 3/9 Details SourceIn Vitro
In Vitro
Yao et al., Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237 (Peer Reviewed) (In Vitro) (not included in the study count) In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) HCQ is more potent than CQ _in vitro_ for inhibiting SARS-CoV-2. Simulates HCQ concentration in lung fluid and provides dosingrecommendations.
See also .
academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1325/6007043 sciencedirect.com/science/article/pii/S0924857920304672 Yao et al., 3/9/2020, peer-reviewed, 16 authors.Share Tweet
Submit Corrections or Comments3/6 Late
Chen et al., J. Zhejiang University (Med Sci), doi:10.3785/j.issn.1008-9292.2020.03.03 (Peer Reviewed) progression, ↓29.0%, p=0.57 A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19) Details 30 moderate hospitalized cases, all recovered. Time to RNA negative comparable. Less frequent radiological progression with HCQ but not statistically significant. One HCQ patient developed to a severe case. Treatment group 4 years older a.. 3/6 Details SourceLate treatment study Late treatment study Chen et al., J. Zhejiang University (Med Sci), doi:10.3785/j.issn.1008-9292.2020.03.03 (Peer Reviewed) A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19) 30 moderate hospitalized cases, all recovered. Time to RNA negative comparable. Less frequent radiological progression with HCQ but not statistically significant. One HCQ patient developed to a severe case. Treatment group 4 years older and with higher incidence of
hypertension.
risk of radiological progression, 29.0% lower, RR 0.71, _p_ = 0.57, treatment 5 of 15 (33.3%), control 7 of 15 (46.7%). risk of viral+ at day 7, 100% higher, RR 2.00, _p_ = 1.00, treatment 2 of 15 (13.3%), control 1 of 15 (6.7%). Chen et al., 3/6/2020, Randomized Controlled Trial, China, Asia, peer-reviewed, 14 authors.Share Tweet
Submit Corrections or Comments3/4 Late
Colson et al., Int J. Antimicrob Agents, doi: 10.1016/j.ijantimicag.2020.105932. Epub 2020 Mar 4. (Review) (Peer Reviewed) (not included in the study count)review
Chloroquine and Hydroxychloroquine as Available Weapons to FightCOVID-19
Details Recommending CQ and HCQ for COVID-19 based on 20 clinical studies in China and a strong rationale for use. 3/4 Details SourceLate treatment study Late treatment study Colson et al., Int J. Antimicrob Agents, doi: 10.1016/j.ijantimicag.2020.105932. Epub 2020 Mar 4. (Review) (Peer Reviewed) (not included in the study count) Chloroquine and Hydroxychloroquine as Available Weapons to Fight
COVID-19
Recommending CQ and HCQ for COVID-19 based on 20 clinical studies in China and a strong rationale for use. Colson et al., 3/4/2020, peer-reviewed, 5 authors.Share Tweet
Submit Corrections or Comments2/20 Late
Jiang et al., Chin. J. Tuberc. Respir. Dis., 2020, 43, doi:10.3760/cma.j.issn.1001-0939.2020.0019 (Peer Reviewed) Expert Consensus on Chloroquine Phosphate for the Treatment of Novel Coronavirus Pneumonia Details Early trials in China show CQ results in shorter hospital stays and improved patient outcomes. 2/20 Details SourceLate treatment study Late treatment study Jiang et al., Chin. J. Tuberc. Respir. Dis., 2020, 43, doi:10.3760/cma.j.issn.1001-0939.2020.0019 (Peer Reviewed) Expert Consensus on Chloroquine Phosphate for the Treatment of Novel Coronavirus Pneumonia Early trials in China show CQ results in shorter hospital stays and improved patient outcomes. Jiang et al., 2/20/2020, peer-reviewed, 1 author.
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Submit Corrections or Comments2/19 Late
Gao et al., BioScience Trends, 2020, doi:10.5582/bst.2020.01047(Peer Reviewed)
Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies Details Results from 15 clinical trials in China showing CQ is effective. 2/19 Details SourceLate treatment study Late treatment study Gao et al., BioScience Trends, 2020, doi:10.5582/bst.2020.01047
(Peer Reviewed)
Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies Results from 15 clinical trials in China showing CQ is effective. Gao et al., 2/19/2020, peer-reviewed, 3 authors.Share Tweet
Submit Corrections or Comments2/17 Late
Sun, Y., deputy head of the China National Center for Biotechnology Development (News) (not included in the study count)news
Antimalarial drug confirmed effective on COVID-19 Details HCQ under clinical trials in >10 hospitals in China and has shown fairly good efficacy. 2/17 Details SourceLate treatment study Late treatment study Sun, Y., deputy head of the China National Center for Biotechnology Development (News) (not included in the study count) Antimalarial drug confirmed effective on COVID-19 HCQ under clinical trials in >10 hospitals in China and has shown fairly good efficacy. Sun et al., 2/17/2020, preprint, 1 author.
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Submit Corrections or Comments2/11 Late
Xia et al., ChiCTR2000029741 (Preprint) viral+, ↓37.5%, p=0.17 Efficacy of Chloroquine and Lopinavir/ Ritonavir in mild/general novel coronavirus (CoVID-19) infections: a prospective, open-label, multicenter randomized controlled clinical study Details Early results from a very small trial, reported within the application for a later trial. Very minimal details are provided, but we include this as the earliest published results. For COVID-19 patients with pneumonia the viral negative co.. 2/11 Details SourceLate treatment study Late treatment study Xia et al., ChiCTR2000029741 (Preprint) Efficacy of Chloroquine and Lopinavir/ Ritonavir in mild/general novel coronavirus (CoVID-19) infections: a prospective, open-label, multicenter randomized controlled clinical study Early results from a very small trial, reported within the application for a later trial. Very minimal details are provided, but we include this as the earliest published results. For COVID-19 patients with pneumonia the viral negative conversion rate was 50% (5/10) with CQ versus 20% (3/15) with lopinavir/ritonavir. risk of no virological cure, 37.5% lower, RR 0.62, _p_ = 0.17, treatment 5 of 10 (50.0%), control 12 of 15 (80.0%). Xia et al., 2/11/2020, retrospective, China, Asia, preprint, 1
author.
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Submit Corrections or Comments2/4 In Vitro
Wang et al., Cell Res. 30, 269–271, doi:L10.1038/s41422-020-0282-0 (Peer Reviewed) (In Vitro) (not included in the study count)_in vitro_
Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro Details _In vitro_ study, not included in the study count or percentages. Remdesivir and CQ potently blocked virus infection _in vitro_. 2/4 Details SourceIn Vitro
In Vitro
Wang et al., Cell Res. 30, 269–271, doi:L10.1038/s41422-020-0282-0 (Peer Reviewed) (In Vitro) (not included in the study count) Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro _In vitro_ study, not included in the study count or percentages. Remdesivir and CQ potently blocked virus infection _in vitro_. Wang et al., 2/4/2020, peer-reviewed, 10 authors.Share Tweet
Submit Corrections or Comments2017 N/A
Chhonker et al., Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Sciences, 22 Nov 2017, 1072:320-327 doi:10.1016/j.jchromb.2017.11.026 (Peer Reviewed) (not included in the study count)dosing study
Simultaneous quantitation of hydroxychloroquine and its metabolites in mouse blood and tissues using LC-ESI-MS/MS: An application for pharmacokinetic studies Details Presents a method for quantification of HCQ in mouse blood and tissues. They show a lung concentration significantly higher than other organs, and about 30 times the bloodconcentration.
2017 Details SourceN/A
N/A
Chhonker et al., Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Sciences, 22 Nov 2017, 1072:320-327 doi:10.1016/j.jchromb.2017.11.026 (Peer Reviewed) (not included in the study count) Simultaneous quantitation of hydroxychloroquine and its metabolites in mouse blood and tissues using LC-ESI-MS/MS: An application for pharmacokinetic studies Presents a method for quantification of HCQ in mouse blood and tissues. They show a lung concentration significantly higher than other organs, and about 30 times the blood concentration. Chhonker et al., 1/1/2017, peer-reviewed, 5 authors.Share Tweet
Submit Corrections or Comments2014 Animal
Browning, D., Pharmacology of Chloroquine and Hydroxychloroquine, 2014, 35-63, doi:10.1007/978-1-4939-0597-3_2 (Peer Reviewed) (not included in the study count)animal study
Pharmacology of Chloroquine and Hydroxychloroquine Details Review of the pharmacology of CQ and HCQ. Some notable points: - HCQ and CQ are equipotent but CQ is more toxic, the therapeutic ratio is higher for HCQ. - Concentrations in different tissues can vary >10x, in particular the concentratio.. 2014 Details SourceAnimal study
Animal study
Browning, D., Pharmacology of Chloroquine and Hydroxychloroquine, 2014, 35-63, doi:10.1007/978-1-4939-0597-3_2 (Peer Reviewed) (not included in the study count) Pharmacology of Chloroquine and Hydroxychloroquine Review of the pharmacology of CQ and HCQ. Some notable points: - HCQ and CQ are equipotent but CQ is more toxic, the therapeutic ratio is higher for HCQ. - Concentrations in different tissues can vary >10x, in particular the concentration in the lung is much higher in animal experiments. - Tissue uptake as a function of dosage is nonlinear. Browning et al., 1/1/2014, peer-reviewed, 1 author.Share Tweet
Submit Corrections or Comments2014 In Vitro
de Wilde et al., Antimicrobial Agents and Chemotherapy, Jul 2014, 58:8, 4875-4884, doi:10.1128/AAC.03011-14 (Peer Reviewed) (In Vitro) (not included in the study count)_in vitro_
Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture Details CQ inhibits SARS-CoV, MERS-CoV, and HCoV-229E-GFP replication in the low-micromolar range. 2014 Details SourceIn Vitro
In Vitro
de Wilde et al., Antimicrobial Agents and Chemotherapy, Jul 2014, 58:8, 4875-4884, doi:10.1128/AAC.03011-14 (Peer Reviewed) (In Vitro) (not included in the study count) Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture CQ inhibits SARS-CoV, MERS-CoV, and HCoV-229E-GFP replication in the low-micromolar range. de Wilde et al., 1/1/2014, peer-reviewed, 9 authors.Share Tweet
Submit Corrections or Comments2012 Animal
Yan et al., Cell Research, 23, 300–302, doi:10.1038/cr.2012.165 (Peer Reviewed) (not included in the study count)animal study
Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model Details CQ, a known autophagy inhibitor that is in clinical use, can efficiently ameliorate acute lung injury and dramatically improve the survival rate in mice infected with live avian influenza A H5N1 virus. 2012 Details SourceAnimal study
Animal study
Yan et al., Cell Research, 23, 300–302, doi:10.1038/cr.2012.165 (Peer Reviewed) (not included in the study count) Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model CQ, a known autophagy inhibitor that is in clinical use, can efficiently ameliorate acute lung injury and dramatically improve the survival rate in mice infected with live avian influenza A H5N1 virus. Yan et al., 1/1/2012, peer-reviewed, 8 authors.Share Tweet
Submit Corrections or Comments2009 Animal
Keyaerts et al., Antimicrob. Agents Chemother, August 2009, 53(8), doi:0.1128/AAC.01509-08 (Peer Reviewed) (not included in the studycount)
animal study
Antiviral Activity of Chloroquine against Human Coronavirus OC43 Infection in Newborn Mice Details CQ inhibits HCoV-OC43 replication in HRT-18 cells. A lethal HCoV-OC43 infection in newborn C57BL/6 mice can be treated with CQ acquired transplacentally or via maternal milk. The highest survival rate (98.6%) was found when mother mice we.. 2009 Details SourceAnimal study
Animal study
Keyaerts et al., Antimicrob. Agents Chemother, August 2009, 53(8), doi:0.1128/AAC.01509-08 (Peer Reviewed) (not included in the studycount)
Antiviral Activity of Chloroquine against Human Coronavirus OC43 Infection in Newborn Mice CQ inhibits HCoV-OC43 replication in HRT-18 cells. A lethal HCoV-OC43 infection in newborn C57BL/6 mice can be treated with CQ acquired transplacentally or via maternal milk. The highest survival rate (98.6%) was found when mother mice were treated daily with a concentration of 15 mg of CQ per kg of body weight. Survival rates declined in a dose-dependent manner, with 88% survival when treated with 5 mg/kg CQ and 13% survival when treated with 1 mg/kg CQ. CQ can be highly effective against HCoV-OC43 infection in newborn mice and may be considered as a future drug against HCoVs. Keyaerts et al., 1/1/2009, peer-reviewed, 7 authors.Share Tweet
Submit Corrections or Comments2008 In Vitro
Kono et al., Antiviral Research, 77:2, February 2008, 150-152, 10.1016/j.antiviral.2007.10.011 (Peer Reviewed) (In Vitro) (not included in the study count)_in vitro_
Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine: Involvement of p38 MAPK and ERK Details CQ significantly decreased viral replication of HCoV-229E at concentrations lower than in clinical usage. CQ affects the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK). p38MAPK i..
2008 Details SourceIn Vitro
In Vitro
Kono et al., Antiviral Research, 77:2, February 2008, 150-152, 10.1016/j.antiviral.2007.10.011 (Peer Reviewed) (In Vitro) (not included in the study count) Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine: Involvement of p38 MAPK and ERK CQ significantly decreased viral replication of HCoV-229E at concentrations lower than in clinical usage. CQ affects the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK). p38 MAPK inhibitor, SB203580, inhibits CPE induced by HCoV-229E infection and viral replication. Kono et al., 1/1/2008, peer-reviewed, 6 authors.Share Tweet
Submit Corrections or Comments2006 In Vitro
Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(06)70361-9 (Peer Reviewed) (In Vitro) (not included in the study count)_in vitro_
New insights into the antiviral effects of chloroquine Details Update to 2003 paper, not included in the study count or percentages. Hypothesis of CQ inhibiting SARS replication has been confirmed in two in-vitro studies. CQ affected an early stage of SARS replication. 2006 Details SourceIn Vitro
In Vitro
Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(06)70361-9 (Peer Reviewed) (In Vitro) (not included in the study count) New insights into the antiviral effects of chloroquine Update to 2003 paper, not included in the study count or percentages. Hypothesis of CQ inhibiting SARS replication has been confirmed in two in-vitro studies. CQ affected an early stage of SARS replication. Savarino et al., 1/1/2006, peer-reviewed, 5 authors.Share Tweet
Submit Corrections or Comments2005 In Vitro
Vincent et al., Virol. J. 2:69, 2005, doi:10.1186/1743-422X-2-69 (Peer Reviewed) (In Vitro) (not included in the study count)_in vitro_
Chloroquine is a potent inhibitor of SARS coronavirus infection andspread
Details _In vitro_ study, SARS-CoV-1, not included in the study count or percentages. CQ has strong antiviral effects on SARS CoV infection when cells treated either before or after exposure, suggesting prophylactic and treatment use. Describesthr..
2005 Details SourceIn Vitro
In Vitro
Vincent et al., Virol. J. 2:69, 2005, doi:10.1186/1743-422X-2-69 (Peer Reviewed) (In Vitro) (not included in the study count) Chloroquine is a potent inhibitor of SARS coronavirus infection andspread
_In vitro_ study, SARS-CoV-1, not included in the study count or percentages. CQ has strong antiviral effects on SARS CoV infection when cells treated either before or after exposure, suggesting prophylactic and treatment use. Describes three mechanisms by which the drug might work and suggests it may have both a prophylactic and therapeutic role in coronavirus infections. Vincent et al., 1/1/2005, peer-reviewed, 8 authors.Share Tweet
Submit Corrections or Comments2004 In Vitro
Keyaerts et al., Biochem. Biophys. Res. Comm., 323:1, 8 October 2004, doi:10.1016/j.bbrc.2004.08.085 (Peer Reviewed) (In Vitro) (not included in the study count)_in vitro_
In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine Details _In vitro_ study, SARS-CoV-1, not included in the study count or percentages. IC50 of CQ for antiviral activity (8.8) is significantly lower than cytostatic activity CC50 (261.3), selectivity index of 30. IC50 for inhibition of SARS-CoV in..
2004 Details SourceIn Vitro
In Vitro
Keyaerts et al., Biochem. Biophys. Res. Comm., 323:1, 8 October 2004, doi:10.1016/j.bbrc.2004.08.085 (Peer Reviewed) (In Vitro) (not included in the study count) In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine _In vitro_ study, SARS-CoV-1, not included in the study count or percentages. IC50 of CQ for antiviral activity (8.8) is significantly lower than cytostatic activity CC50 (261.3), selectivity index of 30. IC50 for inhibition of SARS-CoV _in vitro_ approximates the plasma concentrations of CQ reached during treatment of acute malaria. CQ may be considered for immediate use in the prevention and treatment of SARS-CoV infections. Keyaerts et al., 1/1/2004, peer-reviewed, 5 authors.Share Tweet
Submit Corrections or Comments2003 Theory
Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(03)00806-5 (Peer Reviewed) (Theory) (not included in the study count)theory
Effects of chloroquine on viral infections: an old drug againsttoday's diseases
Details Not included in the study count or percentages. Discussion/review noting that CQ exerts antiviral effects, inhibiting the replication of several viruses including members of the flaviviruses, retroviruses, and coronaviruses. Notesthat CQ..
2003 Details SourceTheory
Theory
Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(03)00806-5 (Peer Reviewed) (Theory) (not included in the study count) Effects of chloroquine on viral infections: an old drug againsttoday's diseases
Not included in the study count or percentages. Discussion/review noting that CQ exerts antiviral effects, inhibiting the replication of several viruses including members of the flaviviruses, retroviruses, and coronaviruses. Notes that CQ has immunomodulatory effects, suppressing the production/release of tumour necrosis factor α and interleukin 6, which mediate the inflammatory complications of severalviral diseases.
Savarino et al., 1/1/2003, peer-reviewed, 5 authors.Share Tweet
Submit Corrections or Comments1918 N/A
Burrows, E., Medical Record, 97:6, 235, Feb 7, 1920 (Peer Reviewed) (not included in the study count) A confirmatory report upon the abortive action of quininedihydrochloride
Details Quinine was found to be effective for the Spanish Flu in 1918. 1918 Details SourceN/A
N/A
Burrows, E., Medical Record, 97:6, 235, Feb 7, 1920 (Peer Reviewed) (not included in the study count) A confirmatory report upon the abortive action of quininedihydrochloride
Quinine was found to be effective for the Spanish Flu in 1918. Burrows et al., 1/1/1918, peer-reviewed, 1 author.Share Tweet
Submit Corrections or Comments1901 N/A
Yeo, B., 1901 (Peer Reviewed) (not included in the study count) A manual of medical treatment or clinical therapeutics Details Quinine is refered to as "the remedy that is most deserving of confidence in the treatment of influenza". 1901 Details SourceN/A
N/A
Yeo, B., 1901 (Peer Reviewed) (not included in the study count) A manual of medical treatment or clinical therapeutics Quinine is refered to as "the remedy that is most deserving of confidence in the treatment of influenza". Yeo et al., 1/1/1901, peer-reviewed, 1 author.Share Tweet
Submit Corrections or Comments1894 Animal
Mossé, Lancet, Nov 3, 1894 (Peer Reviewed) (not included in thestudy count)
animal study
Pathogenesis and Treatment of Influenza Details Lancet study showing quinine protected rabbits from influenza and recommending use for prophylaxis andtreatment.
1894 Details SourceAnimal study
Animal study
Mossé, Lancet, Nov 3, 1894 (Peer Reviewed) (not included in thestudy count)
Pathogenesis and Treatment of Influenza Lancet study showing quinine protected rabbits from influenza and recommending use for prophylaxis and treatment. Mossé et al., 1/1/1894, peer-reviewed, 1 author.Share Tweet
Submit Corrections or Comments1890 N/A
Le Grelot (News) (not included in the study count)news
Quinine use for the Russian influenze pandemic if 1889-1890 Details Quinine and antipyrine, a bitherapy for defying death during the Russian influenza pandemic of 1889-1890 (around 40,000 deaths in France at the beginning of 1890). 1890 Details SourceN/A
N/A
Le Grelot (News) (not included in the study count) Quinine use for the Russian influenze pandemic if 1889-1890 Quinine and antipyrine, a bitherapy for defying death during the Russian influenza pandemic of 1889-1890 (around 40,000 deaths in France at the beginning of 1890). Le Grelot et al., 1/1/1890, preprint, 1 author.Share Tweet
Submit Corrections or Comments1889 N/A
Edwin Wiley Grove (News) (not included in the study count)news
Laxative Bromo Quinine Details Quinine has been used for respiratory infections since 1889. Not included in the study count or percentages, just as an interesting observation. 1889 Details SourceN/A
N/A
Edwin Wiley Grove (News) (not included in the study count) Laxative Bromo Quinine Quinine has been used for respiratory infections since 1889. Not included in the study count or percentages, just as an interestingobservation.
Edwin Wiley Grove et al., 1/1/1889, preprint, 1 author.Share Tweet
Submit Corrections or Comments For search methods, inclusion criteria, effect extraction criteria (more serious outcomes have priority), PRISMA answers, and statistical methods see hcqmeta.com . In Vitro, Ex Vivo, Meta, Theory, Safety, Review, News, and Retracted items are not included in the study count. There is a total of 394 items. Studies with preprints and journal versions are listed under the earlierpreprint date.
Please send us corrections, updates, or comments. _Vaccines and treatments are both extremely valuable and complementary. All practical, effective, and safe means should be used. Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. Denying the efficacy of any method increases the risk of COVID-19 becoming endemic; and increases mortality, morbidity, and collateral damage. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. Treatment protocols for physicians are available fromthe FLCCC ._
Select images to upload or use drag and drop to submit images Thanks for your feedback! Please search before submitting papers and note that studies are listed under the date they were first available, which may be the date of an earlier preprint. SubmitShare
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