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Introduction
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Analysis with Exclusions
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All studies
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With exclusions
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Home   COVID-19 treatment studies for Hydroxychloroquine  COVID-19 treatment studies for HCQ  C19 studies: HCQ  HCQ   Select treatmentSelect treatmentTreatmentsTreatments
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97% of the 32 early treatment studies report a positive effect (13 statistically significant in isolation).
Meta analysis using the most serious outcome reported shows 64% [54‑71%] improvement for the 32 early treatment studies. Results are similar after exclusion based sensitivity analysis and after restriction to peer-reviewed studies. Restricting to the 8 RCTs shows 46% [16‑65%] improvement, and restricting to the 13 mortality results shows 75% [60‑84%] lower mortality.
Late treatment is less successful, with only 68% of the 199 studies reporting a positive effect. Very late stage treatment is not effective and may be harmful, especially when using excessive dosages.
83% of Randomized Controlled Trials (RCTs) for early, PrEP, or PEP treatment report positive effects, the probability of this happening for an ineffective treatment is 0.0038.
There is evidence of bias towards publishing negative results. 76% of prospective studies report positive effects, compared to 71% of retrospective studies. Studies from North America are 2.7 times more likely to report negative results than studies from the rest of the world combined, p = 0.0000000477. The probability that an ineffective treatment generated results as positive as the 294 studies is estimated to be 1 in 263 trillion.
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 treatment arm.
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 collateral damage.
All data to reproduce this paper and the sources are in the appendix. See [Ladapo, Prodromos, Risch, Risch (B)] for other meta analyses showing efficacy when HCQ is used early.
Total294 studies4,723 authors412,766 patients
Positive effects213 studies3,331 authors290,476 patients
Early treatment 64% improvement RR 0.36 [0.29-0.46]
Late treatment 19% improvement RR 0.81 [0.76-0.86]
    
  
A
00.250.50.7511.251.51.752+Gautret66%0.34 [0.17-0.68]2.4gviral+6/2014/16Improvement, RR [CI]Dose (4d)TreatmentControlHuang (RCT)92%0.08 [0.01-1.32]4.0g (c)no recov.0/106/12Esper64%0.36 [0.15-0.87]2.0ghosp.8/41212/224Ashraf68%0.32 [0.10-1.10]1.6gdeath10/772/5Huang (ES)59%0.41 [0.26-0.64]2.0g (c)viral time32 (n)37 (n)Guérin61%0.39 [0.02-9.06]2.4gdeath0/201/34Chen (RCT)72%0.28 [0.11-0.74]1.6gviral time18 (n)12 (n)Derwand79%0.21 [0.03-1.47]1.6gdeath1/14113/377Mitjà (RCT)16%0.84 [0.35-2.03]2.0ghosp.8/13611/157Skipper (RCT)37%0.63 [0.21-1.91]3.2ghosp./death5/2318/234Hong65%0.35 [0.13-0.72]n/aviral+42 (n)48 (n)Bernabeu-Wittel59%0.41 [0.36-0.95]2.0gdeath189 (n)83 (n)Yu (ES)85%0.15 [0.02-1.05]1.6gdeath1/73238/2,604Ly56%0.44 [0.26-0.75]2.4gdeath18/11629/110Ip55%0.45 [0.11-1.85]n/adeath2/9744/970Heras96%0.04 [0.02-0.09]n/adeath8/7016/30Kirenga26%0.74 [0.47-1.17]n/arecov. time29 (n)27 (n)Sulaiman64%0.36 [0.17-0.80]2.0gdeath7/1,81754/3,724Guisado-Vasco (ES)67%0.33 [0.05-1.55]n/adeath2/65139/542Szente Fonseca64%0.36 [0.20-0.67]2.0ghosp.25/17589/542Cadegiani81%0.19 [0.01-3.88]1.6gdeath0/1592/137Simova94%0.06 [0.00-1.13]2.4ghosp.0/332/5Omrani (RCT)12%0.88 [0.26-2.94]2.4ghosp.7/3044/152Agusti68%0.32 [0.06-1.67]2.0gprogression2/874/55Su85%0.15 [0.04-0.57]1.6gprogression261 (n)355 (n)Amaravadi (RCT)60%0.40 [0.13-1.28]3.2gno recov.3/156/12Roy2%0.98 [0.45-2.20]n/arecov. time14 (n)15 (n)Mokhtari70%0.30 [0.20-0.45]2.0gdeath27/7,295287/21,464Million83%0.17 [0.06-0.48]2.4gdeath5/8,31511/2,114Sobngwi (RCT)52%0.48 [0.09-2.58]1.6gno recov.2/954/92Rodrigues (RCT)-200%3.00 [0.13-71.6]3.2ghosp.1/420/42Sawanpanyalert42%0.58 [0.18-1.91]variesprogressionn/an/aEarly treatment64%0.36 [0.29-0.46]148/20,390996/34,23164% improvementAll 32 hydroxychloroquine COVID-19 early treatment studieshcqmeta.com Oct 17, 2021Tau​2 = 0.20; I​2 = 52.9%; Z = 8.20Effect extraction pre-specified, see appendixFavors HCQFavors control
    
  
B
    
  
C
    
  
D
Figure 1. A. Random effects meta-analysis of all early treatment studies. This plot shows pooled effects, analysis for individual outcomes is below, and more details on pooled effects can be found in the heterogeneity section. Effect extraction is pre-specified, using the most serious outcome reported. Simplified dosages are shown for comparison, these are the total dose in the first four days. Chloroquine is indicated with (c). For details of effect extraction and full dosage information see the appendix. B. Scatter plot of the effects reported in early treatment studies and in all studies. Early treatment is more effective. C and D. Chronological history of all reported effects, with the probability that the observed frequency of positive effects occurred due to random chance from an ineffective treatment.
Introduction
We analyze all significant studies concerning the use of HCQ (or CQ) for COVID-19. Search methods, inclusion criteria, effect extraction criteria (more serious outcomes have priority), all individual study data, PRISMA answers, and statistical methods are detailed in Appendix 1. We present random-effects meta-analysis results for all studies, for studies within each treatment stage, for mortality results only, after exclusion of studies with critical bias, and for Randomized Controlled Trials (RCTs) only. Typical meta analyses involve subjective selection criteria and bias evaluation, requiring an understanding of the criteria and the accuracy of the evaluations. However, the volume of studies presents an opportunity for an additional simple and transparent analysis aimed at detecting efficacy.
If treatment was not effective, the observed effects would be randomly distributed (or more likely to be negative if treatment is harmful). We can compute the probability that the observed percentage of positive results (or higher) could occur due to chance with an ineffective treatment (the probability of >= k heads in n coin tosses, or the one-sided sign test / binomial test). Analysis of publication bias is important and adjustments may be needed if there is a bias toward publishing positive results. For HCQ, we find evidence of a bias toward publishing negative results.
Figure 2 shows stages of possible treatment for COVID-19. Pre-Exposure Prophylaxis (PrEP) refers to regularly taking medication before being infected, in order to prevent or minimize infection. In Post-Exposure Prophylaxis (PEP), medication is taken after exposure but before symptoms appear. Early Treatment refers to treatment immediately or soon after symptoms appear, while Late Treatment refers to more delayed treatment.
    
  
Figure 2. Treatment stages.
Results
Figure 3, Figure 4, and Table 1 show results by treatment stage, and Figure 5 shows a forest plot for a random effects meta-analysis of all studies. Figure 6 and Figure 7 show forest plots restricted to mortality and hospitalization results only.
Early treatment.
97% of early treatment studies report a positive effect, with an estimated reduction of 64% in the effect measured (death, hospitalization, etc.) from the random effects meta-analysis, RR 0.36 [0.29-0.46].
Late treatment.
Late treatment studies are mixed, with 68% showing positive effects, and an estimated reduction of 19% in the random effects meta-analysis. Negative studies mostly fall into the following categories: they show evidence of significant unadjusted confounding, including confounding by indication; usage is extremely late; or they use an excessively high dosage.
Pre-Exposure Prophylaxis.
75% of PrEP studies show positive effects, with an estimated reduction of 30% in the random effects meta-analysis. Negative studies are all studies of systemic autoimmune disease patients which either do not adjust for the different baseline risk of these patients at all, or do not adjust for the highly variable risk within these patients.
Post-Exposure Prophylaxis.
88% of PEP studies report positive effects, with an estimated reduction of 33% in the random effects meta-analysis.
Treatment timeNumber of studies reporting positive results Total number of studiesPercentage of studies reporting positive results Probability of an equal or greater percentage of positive results from an ineffective treatmentRandom effects meta-analysis results
Early treatment 31 32 96.9% 1 in 130 million 64% improvement
RR 0.36 [0.29‑0.46]
p < 0.0001
Late treatment 135 200 67.5% 1 in 2 million 19% improvement
RR 0.81 [0.76‑0.86]
p < 0.0001
Pre‑Exposure Prophylaxis 43 57 75.4% 1 in 13 thousand 30% improvement
RR 0.70 [0.58‑0.84]
p = 0.00014
Post‑Exposure Prophylaxis 7 8 87.5% 1 in 28 33% improvement
RR 0.67 [0.53‑0.83]
p = 0.00043
All studies 213 294 72.4% 1 in 263 trillion 25% improvement
RR 0.75 [0.71‑0.79]
p < 0.0001
Table 1. Results by treatment stage. 3 studies report results for a subset with early treatment, these are not included in the overall results.
    
  
Figure 3. Results by treatment stage.
    
  
    
  
    
  
    
  
Figure 4. Chronological history of results by treatment stage, with the probability that the observed frequency of positive results occurred due to random chance from an ineffective treatment.
    
  
00.250.50.7511.251.51.752+Gautret66%0.34 [0.17-0.68]viral+6/2014/16Improvement, RR [CI]TreatmentControlHuang (RCT)92%0.08 [0.01-1.32]no recov.0/106/12Esper64%0.36 [0.15-0.87]hosp.8/41212/224Ashraf68%0.32 [0.10-1.10]death10/772/5Huang (ES)59%0.41 [0.26-0.64]viral time32 (n)37 (n)Guérin61%0.39 [0.02-9.06]death0/201/34Chen (RCT)72%0.28 [0.11-0.74]viral time18 (n)12 (n)Derwand79%0.21 [0.03-1.47]death1/14113/377Mitjà (RCT)16%0.84 [0.35-2.03]hosp.8/13611/157Skipper (RCT)37%0.63 [0.21-1.91]hosp./death5/2318/234Hong65%0.35 [0.13-0.72]viral+42 (n)48 (n)Bernabeu-Wittel59%0.41 [0.36-0.95]death189 (n)83 (n)Yu (ES)85%0.15 [0.02-1.05]death1/73238/2,604Ly56%0.44 [0.26-0.75]death18/11629/110Ip55%0.45 [0.11-1.85]death2/9744/970Heras96%0.04 [0.02-0.09]death8/7016/30Kirenga26%0.74 [0.47-1.17]recov. time29 (n)27 (n)Sulaiman64%0.36 [0.17-0.80]death7/1,81754/3,724Guisado-Vasco (ES)67%0.33 [0.05-1.55]death2/65139/542Szente Fonseca64%0.36 [0.20-0.67]hosp.25/17589/542Cadegiani81%0.19 [0.01-3.88]death0/1592/137Simova94%0.06 [0.00-1.13]hosp.0/332/5Omrani (RCT)12%0.88 [0.26-2.94]hosp.7/3044/152Agusti68%0.32 [0.06-1.67]progression2/874/55Su85%0.15 [0.04-0.57]progression261 (n)355 (n)Amaravadi (RCT)60%0.40 [0.13-1.28]no recov.3/156/12Roy2%0.98 [0.45-2.20]recov. time14 (n)15 (n)Mokhtari70%0.30 [0.20-0.45]death27/7,295287/21,464Million83%0.17 [0.06-0.48]death5/8,31511/2,114Sobngwi (RCT)52%0.48 [0.09-2.58]no recov.2/954/92Rodrigues (RCT)-200%3.00 [0.13-71.6]hosp.1/420/42Sawanpanyalert42%0.58 [0.18-1.91]progressionn/an/aTau​2 = 0.20; I​2 = 52.9%Early treatment64%0.36 [0.29-0.46]148/20,390996/34,23164% improvementXia38%0.62 [0.32-1.22]viral+5/1012/15Improvement, RR [CI]TreatmentControlChen (RCT)29%0.71 [0.29-1.74]progression5/157/15Zhong80%0.20 [0.08-0.52]viral+5/11517/82Chen (RCT)57%0.43 [0.19-0.97]pneumonia6/3114/31Barbosa-147%2.47 [0.24-25.0]death2/171/21Tang (RCT)21%0.79 [0.38-1.62]viral+11/7514/75Magagnoli11%0.89 [0.45-1.77]death39/14818/163Auld-3%1.03 [0.67-1.57]death33/11429/103Sánchez-Álvarez46%0.54 [0.34-0.84]death322 (n)53 (n)Mallat-203%3.03 [1.11-7.69]viral time23 (n)11 (n)Membrillo de Nov..55%0.45 [0.29-0.71]death27/12321/43Geleris-4%1.04 [0.82-1.32]int./death262/81184/565Alberici43%0.57 [0.24-1.13]death17/729/22Rosenberg-35%1.35 [0.76-2.40]death189/73528/221Shabrawishi15%0.85 [0.45-1.62]viral+12/4515/48Mahévas-20%1.20 [0.40-3.30]death9/848/89Yu60%0.40 [0.22-0.72]death9/48238/502Kim51%0.49 [0.28-0.87]hosp. time22/2240/40Singh5%0.95 [0.74-1.22]death104/910109/910Luo32%0.68 [0.08-5.88]death19 (n)264 (n)Hraiech65%0.35 [0.08-1.56]death2/175/15Ip1%0.99 [0.80-1.22]death432/1,914115/598Goldman22%0.78 [0.40-1.52]death10/10934/288Huang67%0.33 [0.19-0.57]viral time197 (n)176 (n)Kuderer-134%2.34 [1.62-3.21]death45/181121/928Rogado92%0.08 [0.00-0.87]death1/87/9RECOVERY (RCT)-9%1.09 [0.97-1.23]death421/1,561790/3,155Wang6%0.94 [0.75-1.19]death1,866 (n)5,726 (n)Luo-2%1.02 [0.39-2.65]death11/354/13Paccoud11%0.89 [0.23-3.47]death21/3826/46Sbidian-5%1.05 [0.77-1.33]death111/623830/3,792Faíco-Filho81%0.19 [0.00-8.66]viral rate34 (n)32 (n)Fontana50%0.50 [0.16-1.55]death4/122/3Bousquet43%0.57 [0.24-1.36]death5/2723/81Lagier59%0.41 [0.27-0.62]death35/3,11958/618Sosa-García-11%1.11 [0.32-3.78]death7/383/18Komissarov-25%1.25 [0.71-2.21]viral load26/2610/10Mikami47%0.53 [0.41-0.68]death575/2,077231/743Martinez-Lopez33%0.67 [0.39-1.14]death47/1489/19Arshad51%0.49 [0.39-0.60]death162/1,202108/409An3%0.97 [0.57-1.67]viral+31/31195/195Rivera-Izquierdo19%0.81 [0.24-2.76]death215 (n)23 (n)Chen-29%1.29 [0.58-2.86]viral+16/284/9Chen (RCT)24%0.76 [0.20-2.84]viral+4/213/12Cravedi-53%1.53 [0.84-2.80]death36/10110/43Lecronier42%0.58 [0.27-1.24]death9/389/22Trullàs36%0.64 [0.39-1.07]death20/6616/34Gupta-6%1.06 [0.92-1.22]death631/1,761153/454Lyngbakken (RCT)4%0.96 [0.06-14.6]death1/271/26McGrail-70%1.70 [0.41-7.07]death4/333/42Krishnan20%0.80 [0.52-1.21]death86/1446/8Bernaola17%0.83 [0.77-0.89]death236/1,49828/147Kelly-143%2.43 [1.06-5.56]death23/826/52Rivera-2%1.02 [0.67-1.53]death44/17959/327Cavalcanti (RCT)16%0.84 [0.28-2.53]death8/3315/173D'Arminio Monforte34%0.66 [0.39-1.11]death53/19747/92Davido55%0.45 [0.23-0.89]int./hosp.12/8013/40Yu83%0.17 [0.02-1.27]progression1/23132/1,291Berenguer18%0.82 [0.74-0.90]death681/2,618438/1,377Kamran5%0.95 [0.34-2.69]progression11/3495/151Kalligeros-67%1.67 [0.29-9.36]death36 (n)72 (n)Saleemi-21%1.21 [1.00-1.46]viral time65/6520/20Roomi-38%1.38 [0.40-2.76]death13/1446/32Abd-Elsalam (RCT)-20%1.20 [0.38-3.80]death6/975/97Peters-9%1.09 [0.81-1.47]death419/1,59653/353Pinato59%0.41 [0.29-0.58]death30/182181/446Dubernet88%0.12 [0.02-0.88]ICU1/179/19Gonzalez27%0.73 [0.66-0.81]death1,246/8,476341/1,168Pasquini16%0.84 [0.62-1.14]death23/3315/18Catteau32%0.68 [0.62-0.76]death804/4,542957/3,533Di Castelnuovo30%0.70 [0.59-0.84]death386/2,63490/817Fried-27%1.27 [1.18-1.36]death1,048/4,2321,466/7,489Albani18%0.82 [0.61-1.06]death60/211172/605Synolaki24%0.76 [0.49-1.18]death21/9860/214Alamdari55%0.45 [0.22-0.92]death427 (n)32 (n)Heberto54%0.46 [0.22-0.97]death139 (n)115 (n)Lauriola74%0.27 [0.17-0.41]death102/29735/63Ashinyo33%0.67 [0.47-0.96]hosp. time61/6161/61Serrano43%0.57 [0.28-1.18]death6/146/8Ulrich (RCT)-6%1.06 [0.38-2.98]death7/676/61Shoaibi15%0.85 [0.79-0.91]death686/5,0473,923/24,404Lammers32%0.68 [0.47-0.99]death/ICU30/189101/498Ayerbe52%0.48 [0.37-0.62]death237/1,85749/162Almazrou65%0.35 [0.09-1.35]ventilation3/956/66Nachega28%0.72 [0.49-1.06]death69/63028/96Ader (RCT)6%0.94 [0.43-2.05]death11/14512/148Soto-Becerra18%0.82 [0.76-0.89]death346/6921,606/2,630Aparisi63%0.37 [0.27-0.50]death122/60527/49Annie4%0.96 [0.65-1.37]death48/36750/367SOLIDARITY (RCT)-19%1.19 [0.89-1.59]death104/94784/906Guisado-Vasco20%0.80 [0.47-1.26]death127/55814/49Solh-18%1.18 [0.93-1.51]death131/265134/378Ñamendys-Silva32%0.68 [0.48-0.96]death24/5442/64Dubee (RCT)46%0.54 [0.21-1.42]death6/12411/123Lano33%0.67 [0.28-1.31]death56 (n)66 (n)Coll46%0.54 [0.41-0.72]death55/307108/328Frontera (PSM)37%0.63 [0.44-0.91]death121/1,006424/2,467Choi-22%1.22 [1.10-1.35]viral time701/701701/701Tehrani13%0.87 [0.54-1.40]death16/6554/190López64%0.36 [0.14-0.89]progression5/3614/36Salazar-37%1.37 [0.77-2.42]death12/9280/811Rodriguez-Nava-6%1.06 [0.72-1.56]death22/6579/248Maldonado91%0.09 [0.02-0.50]death1/111/1Núñez-Gil8%0.92 [0.87-0.94]death200/686100/268Self (RCT)-6%1.06 [0.57-1.87]death25/24125/236Rodriguez59%0.41 [0.13-1.31]death8/392/4Águila-Gordo67%0.33 [0.09-1.24]death151/34647/70Sheshah80%0.20 [0.09-0.45]death267 (n)33 (n)Boari55%0.45 [0.30-0.68]death41/20225/56Budhiraja65%0.35 [0.24-0.50]death69/83434/142Falcone (PSM)65%0.35 [0.07-1.73]death40/23830/77Qin34%0.66 [0.22-2.00]death3/4375/706Burdick-59%1.59 [0.89-2.83]death142 (n)148 (n)van Halem32%0.68 [0.47-1.00]death34/16447/155Rodriguez-Gonzalez23%0.77 [0.51-1.17]death251/1,14817/60Lambermont32%0.68 [0.48-0.96]death97/22514/22Abdulrahman (PSM)17%0.83 [0.26-2.69]death5/2236/223Capsoni40%0.60 [0.29-1.25]ventilation12/406/12Peng11%0.89 [0.62-1.29]progression29/453256/3,567Modrák59%0.41 [0.19-1.03]death108 (n)105 (n)Ozturk44%0.56 [0.28-1.13]death165/1,1276/23Guglielmetti35%0.65 [0.33-1.30]death181 (n)37 (n)Johnston (RCT)30%0.70 [0.19-2.54]hosp.5/1484/83Alqassieh18%0.82 [0.64-1.05]hosp. time63 (n)68 (n)Bielza22%0.78 [0.59-1.05]death33/91249/539Tan35%0.65 [0.43-0.98]hosp. time8 (n)277 (n)Naseem33%0.67 [0.30-1.53]death77 (n)1,137 (n)Orioli13%0.87 [0.26-2.94]death8/553/18De Luna-105%2.05 [0.29-14.6]death15/1321/18Signes-Costa47%0.53 [0.37-0.75]death4,854 (n)993 (n)Matangila55%0.45 [0.07-1.27]death25/1478/13Cangiano73%0.27 [0.12-0.61]death5/3337/65Taccone25%0.75 [0.58-0.95]death449/1,308183/439Chari33%0.67 [0.37-1.22]death8/29195/473Güner77%0.23 [0.03-1.76]ICU604 (n)100 (n)Vernaz (PSM)15%0.85 [0.42-1.70]death12/9316/105Texeira-79%1.79 [0.95-3.38]death17/6514/96Psevdos-63%1.63 [0.55-4.84]death17/523/15Sands-70%1.70 [1.18-2.42]death101/97356/696Lotfy-25%1.25 [0.39-3.96]death6/995/103Sarfaraz-45%1.45 [0.98-2.15]death40/9427/92Yegerov95%0.05 [0.00-0.75]death0/2320/1,049Li-40%1.40 [0.99-1.98]viral time18 (n)19 (n)Li50%0.50 [0.23-1.10]no disch.14 (n)14 (n)Di Castelnuovo40%0.60 [0.50-0.70]death3,270 (n)1,000 (n)Roig16%0.84 [0.49-1.44]death33/677/12Ubaldo18%0.82 [0.52-1.28]death17/255/6Ouedraogo33%0.67 [0.28-1.62]death397 (n)59 (n)Hernandez-C.. (RCT)12%0.88 [0.51-1.53]death106 (n)108 (n)Purwati (RCT)66%0.34 [0.26-0.44]viral+38/121111/119Thompson (RCT)-6%1.06 [0.57-1.87]death25/24125/236Lora-Tamayo50%0.50 [0.44-0.56]death7,192 (n)1,361 (n)Awad-19%1.19 [0.84-1.70]death56/18837/148Lamback9%0.91 [0.41-2.00]death11/10111/92Gonzalez (RCT)63%0.37 [0.08-1.73]death2/336/37Salvador33%0.67 [0.40-1.03]death28/12158/124Martin-Vicente59%0.41 [0.18-0.94]death37/911/1Stewart1%0.99 [0.73-1.35]death66/578188/1,243Stewart-130%2.30 [1.49-3.54]death32/10833/256Stewart-9%1.09 [0.76-1.56]death212/1,157203/1,101Stewart-90%1.90 [0.91-4.10]death46/20847/1,334Stewart-16%1.16 [0.90-1.51]