Source: hcqmeta.com
• HCQ is effective for COVID-19. The probability that an ineffective treatment generated results as positive as the 235 studies to date is estimated to be 1 in 6 quadrillion (p = 0.00000000000000018).
• Early treatment is most successful, with 100% of 29 studies reporting a positive effect (13 statistically significant in isolation) and an estimated reduction of 65% in the effect measured (death, hospitalization, etc.) using a random effects meta-analysis, RR 0.35 [0.25-0.50].
• 92% of Randomized Controlled Trials (RCTs) for early, PrEP, or PEP treatment report positive effects, the probability of this happening for an ineffective treatment is 0.0017.
• There is evidence of bias towards publishing negative results. 88% of prospective studies report positive effects, and only 73% of retrospective studies do.
• Studies from North America are 3.8 times more likely to report negative results than studies from the rest of the world combined, p = 0.0000000015.
• All data to reproduce this paper and the sources are in the appendix.
| Total | 235 studies | 3,740 authors | 359,862 patients |
| Positive effects | 179 studies | 2,743 authors | 251,797 patients |
| Early treatment | 65% improvement | RR 0.35 [0.25-0.50] |
| Late treatment | 23% improvement | RR 0.77 [0.71-0.83] |
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.
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 shows a forest plot restricted to mortality results only.Early treatment. 100% of early treatment studies report a positive effect, with an estimated reduction of 65% in the effect measured (death, hospitalization, etc.) from the random effects meta-analysis, RR 0.35 [0.25-0.50].
Late treatment.
Late treatment studies are mixed, with 72% showing positive effects, and an estimated reduction of 23% 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.
77% of PrEP studies show positive effects, with an estimated reduction of 29% 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.
86% of PEP studies report positive effects, with an estimated reduction of 34% in the random effects meta-analysis.
| Treatment time | Number of studies reporting positive results | Total number of studies | Percentage of studies reporting positive results | Probability of an equal or greater percentage of positive results from an ineffective treatment | Random effects meta-analysis results |
| Early treatment | 30 | 30 | 100% | 0.00000000093 1 in 1 billion | 65% improvement RR 0.35 [0.25‑0.50] p < 0.0001 |
| Late treatment | 113 | 158 | 71.5% | 0.000000031 1 in 32 million | 23% improvement RR 0.77 [0.71‑0.83] p < 0.0001 |
| Pre‑Exposure Prophylaxis | 33 | 43 | 76.7% | 0.0003 1 in 3 thousand | 29% improvement RR 0.71 [0.58‑0.87] p = 0.00078 |
| Post‑Exposure Prophylaxis | 6 | 7 | 85.7% | 0.062 1 in 16 | 34% improvement RR 0.66 [0.53‑0.83] p = 0.00043 |
| All studies | 179 | 235 | 76.2% | 0.00000000000000018 1 in 6 quadrillion | 28% improvement RR 0.72 [0.68‑0.77] p < 0.0001 |
Randomized Controlled Trials (RCTs)
Randomized Controlled Trials (RCTs) minimize one source of bias and can provide a higher level of evidence. Results restricted to RCTs are shown in Figure 7, Figure 8, and Table 2. Even with the small number of RCTs to date, they confirm efficacy for early treatment.
While late treatment RCTs are dominated by the very late stage and large RECOVERY/SOLIDARITY trials, prophylaxis and early treatment studies show 32% improvement in random effects meta-analysis, RR 0.68 [0.54‑0.85], p = 0.00068. Early treatment RCTs show 49% improvement, RR 0.51 [0.32‑0.82], p = 0.005.Evidence supports incorporating non-RCT studies. [Concato] find that well-designed observational studies do not systematically overestimate the magnitude of the effects of treatment compared to RCTs.
[Anglemyer] summarized reviews comparing RCTs to observational studies and found little evidence for significant differences in effect estimates.
[Lee] shows that only 14% of the guidelines of the Infectious Diseases Society of America were based on RCTs. Limitations in an RCT can easily outweigh the benefits, for example excessive dosages, excessive treatment delays, or Internet survey bias could easily have a greater effect on results. Ethical issues may prevent running RCTs for known effective treatments. For more on the problems with RCTs see [Deaton, Nichol].
| Treatment time | Number of studies reporting positive results | Total number of studies | Percentage of studies reporting positive results | Probability of an equal or greater percentage of positive results from an ineffective treatment | Random effects meta-analysis results |
| Randomized Controlled Trials | 24 | 30 | 80.0% | 0.00072 1 in 1 thousand | 29% improvement RR 0.71 [0.57‑0.89] p = 0.0029 |
| Randomized Controlled Trials (excluding late treatment) | 12 | 13 | 92.3% | 0.0017 1 in 585 | 32% improvement RR 0.68 [0.54‑0.85] p = 0.00068 |
Analysis with ExclusionsMany meta-analyses for HCQ have been written, most of which have become somewhat obselete due to the continuing stream of more recent studies. Recent analyses with positive conclusions include [IHU Marseille] which considers significant bias from an understanding of each trial, and [Garcia-Albeniz, Ladapo, Prodromos] which focus on early or prophylactic use studies.Meta analyses reporting negative conclusions focus on late treatment studies, tend to disregard treatment delay, tend to follow formulaic evaluations which overlook major issues with various studies, and end up with weighting disproportionate to a reasoned analysis of each study’s contribution. For example, [Axfors] assigns 87% weight to a single trial, the RECOVERY trial [RECOVERY], thereby producing the same result. However, the RECOVERY trial may be the most biased of the studies they included, due to the excessive dosage used, close to the level shown to be very dangerous in [Borba] (OR 2.8), and with extremely sick late stage patients (60% requiring oxygen, 17% ventilation/ECMO, and a very high mortality rate in both arms). There is little reason to suggest that the results from this trial are applicable to more typical dosages or to earlier treatment (10/22: the second version of this study released 10/22 assigns 74% to RECOVERY and 15% to SOLIDARITY [SOLIDARITY], which is the only other trial using a similar excessive dosage).We include all studies in the main analysis, however there are major issues with several studies that could significantly alter the results.
Here, we present an analysis excluding studies with significant issues, including indication of significant unadjusted group differences or confouding by indication, extremely late stage usage >14 days post symptoms or >50% on oxygen at baseline, very minimal detail provided, excessive dosages which have been shown to be dangerous, significant issues with adjustments that could reasonably make substantial differences, and reliance on PCR which may be inaccurate and less indicative of severity than symptoms.
The aim here is not to exclude studies on technicalities, but to exclude studies that clearly have major issues that may significantly change the outcome. We welcome feedback on improvements or corrections to this. The studies excluded are as follows, and the resulting forest plot is shown in Figure 9.
[Ader], very late stage, >50% on oxygen/ventilation at baseline.
[Alamdari], substantial unadjusted confounding by indication likely.
[Albani], substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early period when overall treatment protocols improved dramatically.
[Alghamdi], confounding by indication is likely and adjustments do not consider COVID-19 severity.
[An], results only for PCR status which may be significantly different to symptoms.
[Annie], confounding by indication is likely and adjustments do not consider COVID-19 severity.
[Awad], substantial time varying confounding likely due to declining usage over the early period when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely.
[Barbosa], excessive unadjusted differences between groups.
[Budhiraja], excessive unadjusted differences between groups.
[Cassione], not fully adjusting for the different baseline risk of systemic autoimmune patients.
[Chen], results only for PCR status which may be significantly different to symptoms.
[Chen (B)], results only for PCR status which may be significantly different to symptoms.
[Chen (C)], results only for PCR status which may be significantly different to symptoms.
[Choi], excessive unadjusted differences between groups.
[Cravedi], substantial unadjusted confounding by indication likely.
[de la Iglesia], not fully adjusting for the different baseline risk of systemic autoimmune patients.
[Fitzgerald], not fully adjusting for the baseline risk differences within systemic autoimmune patients.
[Fried], excessive unadjusted differences between groups, substantial unadjusted confounding by indication likely.
[Gautret], excessive unadjusted differences between groups, results only for PCR status which may be significantly different to symptoms.
[Geleris], significant issues found with adjustments.
[Gendebien], not fully adjusting for the baseline risk differences within systemic autoimmune patients.
[Gendelman], not fully adjusting for the different baseline risk of systemic autoimmune patients.
[Gianfrancesco], not fully adjusting for the baseline risk differences within systemic autoimmune patients.
[Gupta], very late stage, >50% on oxygen/ventilation at baseline.
[Hong], results only for PCR status which may be significantly different to symptoms.
[Hraiech], very late stage, ICU patients.
[Huang], significant unadjusted confounding possible.
[Huang (B)], results only for PCR status which may be significantly different to symptoms.
[Huang (C)], results only for PCR status which may be significantly different to symptoms.
[Huh], not fully adjusting for the different baseline risk of systemic autoimmune patients.
[Huh (B)], not fully adjusting for the different baseline risk of systemic autoimmune patients.
[Izoulet], excessive unadjusted differences between groups.
[Kamran], excessive unadjusted differences between groups.
[Kelly], substantial unadjusted confounding by indication likely.
[Konig], not fully adjusting for the baseline risk differences within systemic autoimmune patients.
[Kuderer], substantial unadjusted confounding by indication likely.
[Lamback], substantial time varying confounding likely due to declining usage over the early period when overall treatment protocols improved dramatically.
[Laplana], not fully adjusting for the different baseline risk of systemic autoimmune patients.
[Lecronier], very late stage, >50% on oxygen/ventilation at baseline.
[Lotfy], substantial time varying confounding likely due to declining usage over the early period when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely.
[Luo], substantial unadjusted confounding by indication likely.
[Lyngbakken], results only for PCR status which may be significantly different to symptoms.
[Macias], not fully adjusting for the baseline risk differences within systemic autoimmune patients.
[McGrail], excessive unadjusted differences between groups.
[Mitchell], excessive unadjusted differences between groups.
[Peters], excessive unadjusted differences between groups.
[Psevdos], unadjusted results with no group details, no treatment details, substantial time varying confounding likely due to declining usage over the early period when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely.
[Rangel], not fully adjusting for the different baseline risk of systemic autoimmune patients.
[RECOVERY], excessive dosage, results do not apply to typical dosages.
[Rentsch], not fully adjusting for the baseline risk differences within systemic autoimmune patients, medication adherence unknown and may significantly change results.
[Rodriguez-Nava], substantial unadjusted confounding by indication likely, excessive unadjusted differences between groups.[Roomi], substantial unadjusted confounding by indication likely.
[Roy], no serious outcomes reported and fast recovery in treatment and control groups, there is little room for a treatment to improve results.
[Salazar], substantial unadjusted confounding by indication likely.
[Saleemi], results only for PCR status which may be significantly different to symptoms, substantial unadjusted confounding by indication likely.
[Salvarani], not fully adjusting for the different baseline risk of systemic autoimmune patients.
[Sands], includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons, substantial unadjusted confounding by indication likely.
[Sarfaraz], substantial unadjusted confounding by indication likely, significant unadjusted confounding possible.
[Sbidian], significant issues found with adjustments.
[Shabrawishi], results only for PCR status which may be significantly different to symptoms.
[Singer], not fully adjusting for the baseline risk differences within systemic autoimmune patients.
[Singh], confounding by indication is likely and adjustments do not consider COVID-19 severity.
[Solh], very late stage, >50% on oxygen/ventilation at baseline, substantial unadjusted confounding by indication likely.
[SOLIDARITY], excessive dosage, results do not apply to typical dosages, very late stage, >50% on oxygen/ventilation at baseline.
[Sosa-García], very late stage, >50% on oxygen/ventilation at baseline, substantial unadjusted confounding by indication likely.
[Soto-Becerra], substantial unadjusted confounding by indication likely, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons.
[Stewart], substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early period when overall treatment protocols improved dramatically, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons.
[Stewart (B)], substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early period when overall treatment protocols improved dramatically, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons.
[Stewart (C)], substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early period when overall treatment protocols improved dramatically, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons.
[Stewart (D)], substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early period when overall treatment protocols improved dramatically, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons.
[Stewart (E)], substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early period when overall treatment protocols improved dramatically, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons.
[Stewart (F)], substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early period when overall treatment protocols improved dramatically, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons.
[Stewart (G)], substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early period when overall treatment protocols improved dramatically, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons.
[Tang], results only for PCR status which may be significantly different to symptoms.
[Tehrani], substantial unadjusted confounding by indication likely.
[Texeira], unadjusted results with no group details, no treatment details, substantial time varying confounding likely due to declining usage over the early period when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely.
[Trefond], not fully adjusting for the different baseline risk of systemic autoimmune patients, significant unadjusted confounding possible, excessive unadjusted differences between groups.
[Ubaldo], substantial unadjusted confounding by indication likely, very late stage, ICU patients.
[Ulrich], very late stage, >50% on oxygen/ventilation at baseline.
[Vernaz], substantial time varying confounding likely due to declining usage over the early period when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely.
[Vivanco-Hidalgo], not fully adjusting for the different baseline risk of systemic autoimmune patients.
[Wang], confounding by indication is likely and adjustments do not consider COVID-19 severity.
[Xia], detail too minimal.
[Yegerov], unadjusted results with no group details.
[Zhong], results only for PCR status which may be significantly different to symptoms.
Discussion
Publication bias.
Publishing is often biased towards positive results, which we would need to adjust for when analyzing the percentage of positive results. Studies that require less effort are considered to be more susceptible to publication bias. Prospective trials that involve significant effort are likely to be published regardless of the result, while retrospective studies are more likely to exhibit bias.
For example, researchers may perform preliminary analysis with minimal effort and the results may influence their decision to continue. Retrospective studies also provide more opportunities for the specifics of data extraction and adjustments to influence results.
For HCQ, 87.8% of prospective studies report positive effects, compared to 73.1% of retrospective studies, indicating a bias toward publishing negative results.
Figure 10 shows a scatter plot of results for prospective and retrospective studies.
Figure 11 shows the results by region of the world, for all regions that have > 5 studies. Studies from North America are 3.8 times more likely to report negative results than studies from the rest of the world combined, 53.4% vs. 14.1%, two-tailed z test -6.05, p = 0.0000000015.
[Berry] performed an independent analysis which also showed bias toward negative results for US-based research.
The lack of bias towards positive results is not very surprising. Both negative and positive results are very important given the current use of HCQ for COVID-19 around the world, evidence of which can be found in the studies analyzed here, government protocols, and news reports, for example [AFP, AfricaFeeds, Africanews, Afrik.com, Al Arabia, Al-bab, Anadolu Agency, Anadolu Agency (B), Archyde, Barron’s, Barron’s (B), BBC, Belayneh, A., Bianet, CBS News, Challenge, Dr. Goldin, Efecto Cocuyo, Expats.cz, Face 2 Face Africa, Filipova, France 24, France 24 (B), Franceinfo, Global Times, Government of China, Government of India, Government of Venezuela, GulfInsider, Le Nouvel Afrik, LifeSiteNews, Medical World Nigeria, Medical Xpress, Medical Xpress (B), Middle East Eye, Ministerstva Zdravotnictví, Ministry of Health of Ukraine, Ministry of Health of Ukraine (B), Morocco World News, Mosaique Guinee, Nigeria News World, NPR News, Oneindia, Pan African Medical Journal, Parola, Pilot News, PledgeTimes, Pleno.News, Q Costa Rica, Rathi, Russian Government, Russian Government (B), Teller Report, The Africa Report, The Australian, The BL, The East African, The Guardian, The Indian Express, The Moscow Times, The North Africa Post, The Tico Times, Ukrinform, Vanguard, Voice of America].We also note a bias towards publishing negative results by certain journals and press organizations, with scientists reporting difficulty publishing positive results [Boulware, Meneguesso].
Although 179 studies show positive results, The New York Times, for example, has only written articles for studies that claim HCQ is not effective [The New York Times, The New York Times (B), The New York Times (C)]. As of September 10, 2020, The New York Times still claims that there is clear evidence that HCQ is not effective for COVID-19 [The New York Times (D)]. As of October 9, 2020, the United States National Institutes of Health recommends against HCQ for both hospitalized and non-hospitalized patients [United States National Institutes of Health].
Treatment details.
We focus here on the question of whether HCQ is effective or not for COVID-19. Studies vary significantly in terms of treatment delay, treatment regimen, patients characteristics, and (for the pooled effects analysis) outcomes, as reflected in the high degree of heterogeneity. However, early treatment consistently shows benefits. 100% of early treatment studies report a positive effect, with an estimated reduction of 65% in the effect measured (death, hospitalization, etc.) in the random effects meta-analysis, RR 0.35 [0.25-0.50].
Conclusion
HCQ is an effective treatment for COVID-19. The probability that an ineffective treatment generated results as positive as the 235 studies to date is estimated to be 1 in 6 quadrillion (p = 0.00000000000000018).
100% of early treatment studies report a positive effect, with an estimated reduction of 65% in the effect measured (death, hospitalization, etc.) using a random effects meta-analysis, RR 0.35 [0.25-0.50].
Revisions
This paper is data driven, all graphs and numbers are dynamically generated. We will update the paper as new studies are released or with any corrections. Please submit updates and corrections at the bottom of this page.
10/21: We added studies [Dubee, Martinez-Lopez, Solh]. We received a report that the United States National Institutes of Health is recommending against HCQ for hospitalized and non-hospitalized patients as of October 9, and we added a reference.
10/22: We added [Anglemyer, Ñamendys-Silva]. We updated the discussion of [Axfors] for the second version of this study. We added a table summarizing RCT results.
10/23: We added [Komissarov, Lano]. The second version of the preprint for [Komissarov] includes a comparison with the control group (not reported in the first version). We updated [Lyngbakken] to use the mortality result in the recent journal version of the paper (not reported in the preprint).
10/26: We added [Coll, Goenka, Synolaki].
10/28: We added [Arleo, Choi].10/30: We added [Berenguer, Faíco-Filho].
10/31: We added [Fonseca, Frontera, Tehrani].
11/1: We added [Trullàs].
11/4: We added [Behera, Cadegiani].11/8: We added [Dhibar].
11/9: We added [Self].
11/10: We added [Mathai].
11/12: We added [Simova, Simova (B)].
11/13: We added [Núñez-Gil, Águila-Gordo].
11/14: We added [Sheshah].
11/18: We added [Budhiraja].
11/19: We added [Falcone].
11/20: We added [Omrani].
11/23: We added [Revollo].
11/24: We added [Boari].
11/25: We added [Qin], and we added analysis restricted to mortality results.
11/27: We added [van Halem].
11/28: We added [Lambermont].
11/30: We added [Abdulrahman].
12/1: We added [Capsoni].
12/2: We added [Rodriguez-Gonzalez].
12/4: We added [Modrák, Ozturk, Peng].
12/7: We added [Maldonado].
12/8: We added [Barnabas].
12/9: We added [Agusti, Guglielmetti].
12/11: We added [Jung].
12/13: We added [Bielza].
12/14: We added [Rivera-Izquierdo, Rodriguez-Nava].
12/15: We added [Kalligeros, López].
12/16: We added [Alqassieh, Naseem, Orioli, Sosa-García, Tan].
12/17: We added [Signes-Costa].
12/20: We added [Gönenli, Huh].
12/21: We added [Matangila].
12/22: We added [Taccone].
12/23: We added [Cangiano].
12/24: We added [Su].
12/25: We added [Chari].
12/27: We added the total number of authors and patients.
12/28: We added [Auld, Cordtz].
12/29: We added [Güner, Salazar].
12/31: We added additional details about the studies in the appendix.
1/1: We added [Sands].
1/2: We added the number of patients to the forest plots.
1/3: We added dosage information for early treatment studies.
1/4: We added [Vernaz].
1/5: We added [Sarfaraz].
1/6: We added direct links to the study details in the forest plots.
1/7: We added direct links to the study details in the chronological plots.
1/9: We added [Texeira, Yegerov].
1/11: We added [Rangel].
1/12: We added [Li (B)].
1/15: We updated [Ip] to the published version.
1/16: We added the effect measured for each study in the forest plots.
1/21: We added [Li].
1/24: We added [Desbois, Psevdos]. We moved the analysis with exclusions and mortality analysis to the main text.
2/1: We added [Trefond].
2/2: We added [Bernabeu-Wittel].
2/5: We added [Hernandez-Cardenas].
2/6: We added [Fitzgerald].
2/7: We added [Johnston].
2/9: We added [Ouedraogo].
2/10: We added [Roig, Ubaldo].
2/15: We added [Lora-Tamayo].
2/16: We added [Albani].
2/17: We added [Purwati].
2/18: We added [Awad].
2/20: We added [Lamback].
2/23: We added [Beltran-Gonzalez (B)].
2/25: We added [Bae].
2/26: We added [Amaravadi].
2/28: We added [Rodriguez].
3/2: We added [Pham].
3/3: We added [Pasquini].
3/5: We added [Lotfy].
3/7: We added [Salvador].
3/8: We added [Martin-Vicente].
3/9: We added [Vivanco-Hidalgo].
3/13: We added [Roy].
3/24: We added [Dev].
3/27: We added [Hraiech], and we corrected an error in effect extraction for [Self].
3/28: We added [Stewart].
3/29: We added [Barry].
4/1: We added [Alghamdi].
4/2: We added [Salvarani].
4/4: We updated [Mitjà] for 11 control hospitalizations. There is conflicting data, table S2 lists 12 control hospitalizations, while table 2 shows 11. A previous version of this paper also showed some values corresponding to 12 control hospitalizations in the abstract and table 2.
4/6: We added [Mokhtari].
4/9: We updated [Dubee] to the journal version
.4/14: We added [Seet].
4/20: We added [Alegiani, Alzahrani].
Appendix 1. Methods and Study Results
We performed ongoing searches of PubMed, medRxiv, ClinicalTrials.gov, The Cochrane Library, Google Scholar, Collabovid, Research Square, ScienceDirect, Oxford University Press, the reference lists of other studies and meta-analyses, and submissions to the site c19hcq.com, which regularly receives submissions of both positive and negative studies upon publication.
Search terms were hydroxychloroquine or chloroquine and COVID-19 or SARS-CoV-2, or simply hydroxychloroquine or chloroquine. Automated searches are performed every hour with notifications of new matches.
All studies regarding the use of HCQ or CQ for COVID-19 that report an effect compared to a control group are included in the main analysis. This is a living analysis and is updated regularly.We extracted effect sizes and associated data from all studies. If studies report multiple kinds of effects then the most serious outcome is used in calculations for that study. For example, if effects for mortality and cases are both reported, the effect for mortality is used, this may be different to the effect that a study focused on.
If symptomatic results are reported at multiple times, we used the latest time, for example if mortality results are provided at 14 days and 28 days, the results at 28 days are used. Mortality alone is preferred over combined outcomes. Outcomes with zero events in both arms were not used. Clinical outcome is considered more important than PCR testing status.
When basically all patients recover in both treatment and control groups, preference for viral clearance and recovery is given to results mid-recovery where available (after most or all patients have recovered there is no room for an effective treatment to do better). When results provide an odds ratio, we computed the relative risk when possible, or converted to a relative risk according to [Zhang]. Reported confidence intervals and p-values were used when available, using adjusted values when provided. If multiple types of adjustments are reported including propensity score matching (PSM), the PSM results are used.
When needed, conversion between reported p-values and confidence intervals followed [Altman, Altman (B)], and Fisher’s exact test was used to calculate p-values for event data. If continuity correction for zero values is required, we use the reciprocal of the opposite arm with the sum of the correction factors equal to 1 [Sweeting].
If a study separates HCQ and HCQ+AZ, we use the combined results were possible, or the results for the larger group. Results are all expressed with RR < 1.0 suggesting effectiveness. Most results are the relative risk of something negative. If a study reports relative times, the results are expressed as the ratio of the time for the HCQ group versus the time for the control group.
If a study reports the rate of reduction of viral load, the results are based on the percentage change in the rate. Calculations are done in Python (3.9.1) with scipy (1.5.4), pythonmeta (1.11), numpy (1.19.4), statsmodels (0.12.1), and plotly (4.14.1).The forest plots are computed using PythonMeta [Deng] with the DerSimonian and Laird random effects model (the fixed effect assumption is not plausible in this case).
We received no funding, this research is done in our spare time. We have no affiliations with any pharmaceutical companies or political parties.
We have classified studies as early treatment if most patients are not already at a severe stage at the time of treatment, and treatment started within 5 days after the onset of symptoms, although a shorter time may be preferable. Antivirals are typically only considered effective when used within a shorter timeframe, for example 0-36 or 0-48 hours for oseltamivir, with longer delays not being effective [McLean, Treanor].
A summary of study results is below. Please submit updates and corrections at the bottom of this page.
Early treatment
Effect extraction follows pre-specified rules as detailed above and gives priority to more serious outcomes. Only the first (most serious) outcome is used in calculations, which may differ from the effect a paper focuses on.
| Agusti], 12/9/2020, prospective, Spain, Europe, peer-reviewed, median age 37.0, 13 authors, dosage 400mg bid day 1, 200mg bid days 2-5. | 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. | |
| [Amaravadi], 2/26/2021, Double Blind Randomized Controlled Trial, USA, North America, preprint, 20 authors, dosage 400mg bid days 1-14. | 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 6 of 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. | |
| [Ashraf], 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. | risk of death, 67.5% lower, RR 0.32, p = 0.15, treatment 10 of 77 (13.0%), control 2 of 5 (40.0%). |
| [Bernabeu-Wittel], 8/1/2020, retrospective, Spain, Europe, peer-reviewed, 13 authors, dosage 400mg bid day 1, 200mg bid days 2-7. | risk of death, 59.0% lower, RR 0.41, p = 0.03, treatment 189, control 83. |
| [Cadegiani], 11/4/2020, prospective, Brazil, South America, preprint, 4 authors, dosage 400mg days 1-5. | 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 (with reciprocal of the contrasting arm), 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 (with reciprocal of the contrasting arm), 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 (with reciprocal of the contrasting arm), control group 1. | |
| [Chen], 6/22/2020, Randomized Controlled Trial, China, Asia, preprint, 19 authors, dosage 200mg bid days 1-10. | median time to PCR-, 72.0% lower, relative time 0.28, p = 0.01, treatment 18, control 12. |
| [Derwand], 10/26/2020, retrospective, USA, North America, peer-reviewed, 3 authors, dosage 200mg bid days 1-5. | risk of death, 79.4% lower, RR 0.21, p = 0.12, treatment 1 of 141 (0.7%), control 13 of 377 (3.4%), odds ratio converted to relative risk. |
| risk of hospitalization, 81.6% lower, RR 0.18, p < 0.001, treatment 4 of 141 (2.8%), control 58 of 377 (15.4%), odds ratio converted to relative risk. | |
| [Esper], 4/15/2020, prospective, Brazil, South America, preprint, 15 authors, dosage 800mg day 1, 400mg days 2-7. | risk of hospitalization, 64.0% lower, RR 0.36, p = 0.02, treatment 8 of 412 (1.9%), control 12 of 224 (5.4%). |
| [Fonseca], 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. | 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 per study, odds ratio converted to relative risk, 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 per study, odds ratio converted to relative risk, HCQ vs. anything else. | |
| [Gautret], 3/17/2020, prospective, France, Europe, peer-reviewed, 18 authors, dosage 200mg tid days 1-10. | 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%). |
| [Guisado-Vasco], 10/15/2020, retrospective, Spain, Europe, peer-reviewed, median age 69.0, 25 authors, early treatment subset, dosage not specified. | risk of death, 66.9% lower, RR 0.33, p = 0.19, treatment 2 of 65 (3.1%), control 139 of 542 (25.6%), adjusted per study, odds ratio converted to relative risk, multivariate. |
| [Guérin], 5/31/2020, retrospective, France, Europe, peer-reviewed, 8 authors, dosage 600mg days 1-10, 7-10 days. | 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 (with reciprocal of the contrasting arm). |
| recovery time, 65.0% lower, relative time 0.35, p < 0.001, treatment 20, control 34. | |
| [Heras], 9/2/2020, retrospective, Andorra, Europe, peer-reviewed, median age 85.0, 13 authors, dosage not specified. | 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 per study. |
| [Hong], 7/16/2020, retrospective, South Korea, Asia, peer-reviewed, 7 authors, dosage not specified. | risk of prolonged viral shedding, 64.9% lower, RR 0.35, p = 0.001, treatment 42, control 48, odds ratio converted to relative risk. |
| [Huang (B)], 5/28/2020, prospective, China, Asia, peer-reviewed, 36 authors, early treatment subset, dosage chloroquine 500mg days 1-10, two groups, 500mg qd and 500mg bid. | time to viral-, 59.1% lower, relative time 0.41, p < 0.001, treatment 32, control 37. |
| [Huang (D)], 4/1/2020, Randomized Controlled Trial, China, Asia, peer-reviewed, 18 authors, dosage chloroquine 500mg bid days 1-10. | 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 (with reciprocal of the contrasting arm). |
| risk of no improvement in pneumonia at day 14, 83.0% lower, RR 0.17, p = 0.22, treatment 10, control 12. | |
| [Ip], 8/25/2020, retrospective, database analysis, USA, North America, peer-reviewed, 25 authors, dosage not specified. | 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 per study, odds ratio converted to relative risk. | |
| [Izoulet], 4/21/2020, retrospective, multiple countries, multiple regions, preprint, 1 author, dosage not specified. | risk of death, 85.0% lower, RR 0.15, p < 0.001. |
| [Kirenga], 9/9/2020, prospective, Uganda, Africa, peer-reviewed, 29 authors, dosage not specified. | median time to recovery, 25.6% lower, relative time 0.74, p = 0.20, treatment 29, control 27. |
| [Lagier], 6/25/2020, retrospective, France, Europe, peer-reviewed, 22 authors, dosage 200mg tid days 1-10. | 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 per study. |
| [Ly], 8/21/2020, retrospective, France, Europe, peer-reviewed, mean age 83.0, 21 authors, dosage 200mg tid days 1-10. | 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 per study, odds ratio converted to relative risk. |
| [Mitjà], 7/16/2020, Randomized Controlled Trial, Spain, Europe, peer-reviewed, 45 authors, dosage 800mg day 1, 400mg days 2-7. | 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%). | |
| elative change in viral load from baseline, 2.0% lower, relative load 0.98, treatment 136, control 157, day 7. | |
| [Mokhtari], 4/6/2021, retrospective, Iran, Middle East, peer-reviewed, 11 authors, dosage 400mg bid day 1, 200mg bid days 2-5. | 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 per study, odds ratio converted to relative risk. |
| 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 per study, odds ratio converted to relative risk. | |
| [Omrani], 11/20/2020, Randomized Controlled Trial, Qatar, Middle East, peer-reviewed, 19 authors, dosage 600mg days 1-6. | 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 HCQ vs. control. | |
| [Roy], 3/12/2021, retrospective, database analysis, India, South Asia, preprint, 5 authors, dosage not specified. | relative time to clinical response of wellbeing, 2.4% lower, relative time 0.98, p = 0.96, treatment 14, control 15. |
| [Simova], 11/12/2020, retrospective, Bulgaria, Europe, peer-reviewed, 5 authors, dosage 200mg tid days 1-14. | 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 to zero event (with reciprocal of the contrasting arm). |
| 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 (with reciprocal of the contrasting arm). | |
| [Skipper], 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. | risk of hospitalization, 51.7% lower, RR 0.48, p = 0.19, treatment 5 of 201 (2.5%), control 10 of 194 (5.2%). |
| risk of no recovery at day 14, 20.0% lower, RR 0.80, p = 0.21. | |
| [Su], 12/23/2020, retrospective, China, Asia, peer-reviewed, 9 authors, dosage 400mg days 1-10, 400mg daily for 10-14 days. | risk of disease progression, 84.9% lower, RR 0.15, p = 0.006, treatment 261, control 355, adjusted per study, binary logistic regression. |
| improvement time, 24.0% lower, relative time 0.76, p = 0.02, treatment 261, control 355, adjusted per study, Cox proportional hazards regression. | |
| [Sulaiman], 9/13/2020, prospective, Saudi Arabia, Middle East, preprint, 22 authors, dosage 400mg bid day 1, 200mg bid days 2-5. | 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 per study, odds ratio converted to relative risk. |
| 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 per study, odds ratio converted to relative risk. | |
| [Yu], 8/3/2020, retrospective, China, Asia, preprint, median age 62.0, 6 authors, early treatment subset, dosage 200mg bid days 1-10. | 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. |
Late treatment
Effect extraction follows pre-specified rules as detailed above and gives priority to more serious outcomes. Only the first (most serious) outcome is used in calculations, which may differ from the effect a paper focuses on.
| [Abd-Elsalam], 8/14/2020, Randomized Controlled Trial, Egypt, Africa, peer-reviewed, 10 authors. | 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%). | |
| [Abdulrahman], 11/30/2020, retrospective, Bahrain, Middle East, preprint, 9 authors. | 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 per study, PSM. | |
| [Ader], 10/6/2020, Randomized Controlled Trial, multiple countries, Europe, preprint, baseline oxygen requirements 95.4%, 52 authors. | 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%). |
| [Alamdari], 9/9/2020, retrospective, Iran, West Asia, peer-reviewed, 14 authors. | risk of death, 55.0% lower, RR 0.45, p = 0.03, treatment 427, control 32. |
| [Albani], 8/30/2020, retrospective, Italy, Europe, peer-reviewed, 11 authors. | 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 per study, odds ratio converted to relative risk, HCQ vs. 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 per study, odds ratio converted to relative risk, 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 per study, odds ratio converted to relative risk, 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 per study, odds ratio converted to relative risk, HCQ+AZ vs. neither. | |
| [Alberici], 5/10/2020, retrospective, Italy, Europe, peer-reviewed, 31 authors. | risk of death, 42.9% lower, RR 0.57, p = 0.12, treatment 17 of 72 (23.6%), control 9 of 22 (40.9%), odds ratio converted to relative risk. |
| [Alghamdi], 3/31/2021, retrospective, Saudi Arabia, Middle East, peer-reviewed, 10 authors. | risk of death, 6.9% higher, RR 1.07, p = 0.88, treatment 44 of 568 (7.7%), control 15 of 207 (7.2%). |
| [Almazrou], 10/1/2020, retrospective, Saudi Arabia, Middle East, peer-reviewed, 5 authors. | 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%). | |
| [Alqassieh], 12/10/2020, prospective, Jordan, Middle East, preprint, 10 authors. | hospitalization time, 18.2% lower, relative time 0.82, p = 0.11, treatment 63, control 68. |
| [An], 7/7/2020, retrospective, South Korea, Asia, preprint, 12 authors. | time to viral clearance, 3.0% lower, RR 0.97, p = 0.92, treatment 31, control 195. |
| [Annie], 10/12/2020, retrospective, database analysis, USA, North America, peer-reviewed, 5 authors. | risk of death, 4.3% lower, RR 0.96, p = 0.83, treatment 48 of 367 (13.1%), control 50 of 367 (13.6%), odds ratio converted to relative risk. |
| risk of death, 20.5% higher, RR 1.21, p = 0.46, treatment 29 of 199 (14.6%), control 24 of 199 (12.1%), odds ratio converted to relative risk. | |
| [Aparisi], 10/8/2020, prospective, Spain, Europe, preprint, 18 authors. | risk of death, 63.0% lower, RR 0.37, p = 0.008, treatment 122 of 605 (20.2%), control 27 of 49 (55.1%). |
| [Arshad], 7/1/2020, retrospective, USA, North America, peer-reviewed, 12 authors. | risk of death, 51.3% lower, RR 0.49, p = 0.009, treatment 162 of 1202 (13.5%), control 108 of 409 (26.4%). |
| [Ashinyo], 9/15/2020, retrospective, Ghana, Africa, peer-reviewed, 16 authors. | hospitalization time, 33.0% lower, relative time 0.67, p = 0.03, treatment 61, control 61. |
| [Auld], 4/26/2020, retrospective, USA, North America, peer-reviewed, 14 authors. | risk of death, 2.8% higher, RR 1.03, p = 1.00, treatment 33 of 114 (28.9%), control 29 of 103 (28.2%). |
| [Awad], 2/18/2021, retrospective, USA, North America, peer-reviewed, 4 authors | peer-reviewed, 4 authors. Submit Corrections or Updates. 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 per study, odds ratio converted to relative risk. | |
| 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 per study, odds ratio converted to relative risk. | |
| [Ayerbe], 9/30/2020, retrospective, database analysis, Spain, Europe, peer-reviewed, 3 authors. | 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 per study, odds ratio converted to relative risk. |
| [Barbosa], 4/12/2020, retrospective, USA, North America, preprint, 5 authors. | risk of death, 147.0% higher, RR 2.47, p = 0.58, treatment 2 of 17 (11.8%), control 1 of 21 (4.8%). |
| [Barry], 3/23/2021, retrospective, Saudi Arabia, Middle East, peer-reviewed, 14 authors. | 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 zero event (with reciprocal of the contrasting arm). |
| [Beltran-Gonzalez], 2/23/2021, Double Blind Randomized Controlled Trial, Mexico, North America, peer-reviewed, mean age 53.8, 13 authors. | 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%). | |
| [Berenguer], 8/3/2020, retrospective, Spain, Europe, peer-reviewed, 8 authors | risk of death, 61.9% lower, RR 0.38, p < 0.001, treatment 681 of 2618 (26.0%), control 939 of 1377 (68.2%). |
| [Bernaola], 7/21/2020, retrospective, Spain, Europe, preprint, 7 authors. | risk of death, 17.0% lower, RR 0.83, p < 0.001, treatment 236 of 1498 (15.8%), control 28 of 147 (19.0%). |
| [Bielza], 12/11/2020, retrospective, Spain, Europe, peer-reviewed, median age 87.0, 24 authors | risk of death, 21.5% lower, RR 0.78, p = 0.09, treatment 33 of 91 (36.3%), control 249 of 539 (46.2%). |
| [Boari], 11/17/2020, retrospective, Italy, Europe, peer-reviewed, 20 authors. | risk of death, 54.5% lower, RR 0.45, p < 0.001, treatment 41 of 202 (20.3%), control 25 of 56 (44.6%). |
| [Bousquet], 6/23/2020, prospective, France, Europe, peer-reviewed, 10 authors. | 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 per study, odds ratio converted to relative risk. |
| [Budhiraja], 11/18/2020, retrospective, India, South Asia, preprint, 12 authors | risk of death, 65.4% lower, RR 0.35, p < 0.001, treatment 69 of 834 (8.3%), control 34 of 142 (23.9%). |
| [Cangiano], 12/22/2020, retrospective, Italy, Europe, peer-reviewed, 14 authors. | risk of death, 73.4% lower, RR 0.27, p = 0.03, treatment 5 of 33 (15.2%), control 37 of 65 (56.9%). |
| [Capsoni], 12/1/2020, retrospective, Italy, Europe, preprint, 13 authors. | 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%). |
| [Catteau], 8/24/2020, retrospective, database analysis, Belgium, Europe, peer-reviewed, 11 authors | risk of death, 32.0% lower, RR 0.68, p < 0.001, treatment 804 of 4542 (17.7%), control 957 of 3533 (27.1%). |
| [Cavalcanti], 7/23/2020, Randomized Controlled Trial, Brazil, South America, peer-reviewed, baseline oxygen requirements 41.8%, 14 authors. | 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. | |
| Chari], 12/24/2020, retrospective, multiple countries, multiple regions, peer-reviewed, median age 69.0, 25 authors. | risk of death, 33.1% lower, RR 0.67, p = 0.17, treatment 8 of 29 (27.6%), control 195 of 473 (41.2%). |
| [Chen (B)], 7/10/2020, Randomized Controlled Trial, Taiwan, Asia, peer-reviewed, 19 authors. | 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 (C)], 7/10/2020, retrospective, Taiwan, Asia, peer-reviewed, 19 authors. | risk of no virological cure, 29.0% higher, RR 1.29, p = 0.70, treatment 16 of 28 (57.1%), control 4 of 9 (44.4%), day 14. |
| [Chen (D)], 3/31/2020, Randomized Controlled Trial, China, Asia, preprint, 9 authors. | 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 (E)], 3/6/2020, Randomized Controlled Trial, China, Asia, peer-reviewed, 14 authors. | 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%). | |
| [Choi], 10/27/2020, retrospective, database analysis, South Korea, Asia, peer-reviewed, 8 authors. | median time to PCR-, 22.0% higher, relative time 1.22, p < 0.001, treatment 701, control 701. |
| [Coll], 10/23/2020, retrospective, Spain, Europe, peer-reviewed, median age 61.0, 29 authors | risk of death, 45.6% lower, RR 0.54, p < 0.001, treatment 55 of 307 (17.9%), control 108 of 328 (32.9%). |
| [Cravedi], 7/10/2020, retrospective, USA, multiple countries, North America, multiple regions, peer-reviewed, mean age 60.0, 25 authors. | risk of death, 53.0% higher, RR 1.53, p = 0.17, treatment 36 of 101 (35.6%), control 10 of 43 (23.3%). |
| [D’Arminio Monforte], 7/29/2020, retrospective, Italy, Europe, preprint, 5 authors | 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 per study. |
| [Davido], 8/2/2020, retrospective, France, Europe, peer-reviewed, 14 authors. | 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%). |
| [Di Castelnuovo], 8/25/2020, retrospective, Italy, Europe, peer-reviewed, 110 authors | 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 per study. |
| [Dubee], 10/21/2020, Randomized Controlled Trial, France, Europe, peer-reviewed, median age 77.0, 18 authors. | 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%). | |
| [Dubernet], 8/20/2020, retrospective, France, Africa, peer-reviewed, median age 66.0, 20 authors | 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%). |
| [Falcone], 11/19/2020, prospective, Italy, Europe, peer-reviewed, 19 authors. | reviewed, 19 authors. Submit Corrections or Updates. 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 per study, 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 per study, multivariate Cox regression. | |
| 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 per study, univariate Cox regression. | |
| [Faíco-Filho], 6/21/2020, prospective, Brazil, South America, peer-reviewed, median age 58.0, 6 authors. | 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. | |
| [Fontana], 6/22/2020, retrospective, Italy, Europe, peer-reviewed, 8 authors | risk of death, 50.0% lower, RR 0.50, p = 0.53, treatment 4 of 12 (33.3%), control 2 of 3 (66.7%). |
| [Fried], 8/28/2020, retrospective, database analysis, USA, North America, peer-reviewed, 11 authors. | risk of death, 27.0% higher, RR 1.27, p < 0.001, treatment 1048 of 4232 (24.8%), control 1466 of 7489 (19.6%). |
| [Frontera], 10/26/2020, retrospective, USA, North America, preprint, median age 64.0, 14 authors. | 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 per study, 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 per study, regression. | |
| [Geleris], 5/7/2020, retrospective, USA, North America, peer-reviewed, 12 authors. | 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 per study. |
| [Goldman], 5/27/2020, retrospective, multiple countries, multiple regions, peer-reviewed, 26 authors. | risk of death, 22.3% lower, RR 0.78, p = 0.46, treatment 10 of 109 (9.2%), control 34 of 288 (11.8%). |
| [Gonzalez], 8/21/2020, retrospective, database analysis, Spain, Europe, preprint, 25 authors. | 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 per study, odds ratio converted to relative risk. |
| [Guglielmetti], 12/9/2020, retrospective, Italy, Europe, peer-reviewed, 16 authors. | risk of death, 35.0% lower, RR 0.65, p = 0.22, treatment 181, control 37, adjusted per study, multivariable Cox. |
| [Guisado-Vasco (B)], 10/15/2020, retrospective, Spain, Europe, peer-reviewed, median age 69.0, 25 authors. | 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 per study, odds ratio converted to relative risk. |
| [Gupta], 7/15/2020, retrospective, USA, North America, peer-reviewed, baseline oxygen requirements 87.1%, 34 authors | risk of death, 6.0% higher, RR 1.06, p = 0.41, treatment 631 of 1761 (35.8%), control 153 of 454 (33.7%). |
| [Güner], 12/29/2020, retrospective, Turkey, Middle East, peer-reviewed, 23 authors. | risk of ICU admission, 77.3% lower, RR 0.23, p = 0.16, treatment 604, control 100, IPTW multivariate analysis. |
| [Heberto], 9/12/2020, prospective, Mexico, North America, peer-reviewed, 8 authors | risk of death, 53.6% lower, RR 0.46, p = 0.04, treatment 139, control 115, odds ratio converted to relative risk. |
| risk of mechanical ventilation, 65.6% lower, RR 0.34, p = 0.008, odds ratio converted to relative risk. | |
| [Hernandez-Cardenas], 2/5/2021, Randomized Controlled Trial, Mexico, North America, preprint, 6 authors | 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. | |
| [Hraiech], 5/24/2020, retrospective, France, Europe, peer-reviewed, 8 authors. | 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 (with reciprocal of the contrasting arm), 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 from treatment. | |
| [Huang (C)], 5/28/2020, prospective, China, Asia, peer-reviewed, 36 authors. | 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. | |
| [Ip (B)], 5/25/2020, retrospective, database analysis, USA, North America, peer-reviewed, 32 authors. | 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 per study. |
| [Johnston], 12/9/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 30 authors, dosage 400mg bid day 1, 200mg bid days 2-10 | 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 per study, 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 per study, 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 per study, 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 per study, HCQ + AZ vs. vitamin C + folic acid. | |
| [Kalligeros], 8/5/2020, retrospective, USA, North America, peer-reviewed, 13 authors | risk of death, 67.0% higher, RR 1.67, p = 0.57, treatment 36, control 72. |
| [Kamran], 8/4/2020, prospective, Pakistan, South Asia, preprint, 10 authors. | 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 14, 10.0% higher, RR 1.10, p = 0.52, treatment 349, control 151. | |
| [Kelly], 7/22/2020, retrospective, Ireland, Europe, peer-reviewed, 14 authors. | risk of death, 143.0% higher, RR 2.43, p = 0.03, treatment 23 of 82 (28.0%), control 6 of 52 (11.5%). |
| [Kim], 5/18/2020, retrospective, South Korea, Asia, preprint, 11 authors. | 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. | |
| Komissarov], 6/30/2020, retrospective, Russia, Asia, Europe, preprint, 8 authors. | risk of viral load, 25.0% higher, RR 1.25, p = 0.45, treatment 26, control 10. |
| [Kuderer], 5/28/2020, retrospective, USA, multiple countries, North America, multiple regions, peer-reviewed, 73 authors. | risk of death, 134.2% higher, RR 2.34, p < 0.001, treatment 45 of 181 (24.9%), control 121 of 928 (13.0%), odds ratio converted to relative risk, HCQ+AZ. |
| [Lamback], 2/19/2021, retrospective, Brazil, South America, peer-reviewed, 10 authors. | 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. | |
| [Lambermont], 11/28/2020, retrospective, Belgium, Europe, peer-reviewed, 15 authors | 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 per study. |
| [Lammers], 9/29/2020, prospective, Netherlands, Europe, peer-reviewed, 18 authors | 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 per study. |
| [Lano], 10/21/2020, retrospective, France, Europe, peer-reviewed, median age 73.5, 30 authors. | risk of death, 33.1% lower, RR 0.67, p = 0.28, treatment 56, control 66, adjusted per study, odds ratio converted to relative risk. |
| 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 per study, odds ratio converted to relative risk. | |
| 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). | |
| [Lauriola], 9/14/2020, retrospective, Italy, Europe, peer-reviewed, mean age 71.8, 10 authors. | 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 per study. |
| [Lecronier], 7/11/2020, retrospective, France, Europe, peer-reviewed, baseline oxygen requirements 100.0%, 25 authors, HCQ vs. control | 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%). | |
| [Li], 1/18/2021, retrospective, China, Asia, peer-reviewed, 21 authors. | 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 (B)], 1/12/2021, retrospective, database analysis, China, Asia, preprint, 5 authors. | time to viral-, 40.0% higher, relative time 1.40, p = 0.06, treatment 18, control 19. |
| [Lora-Tamayo], 2/11/2021, retrospective, Spain, Europe, peer-reviewed, 10 authors. | risk of death, 50.5% lower, RR 0.50, p < 0.001, treatment 7192, control 1361, odds ratio converted to relative risk, univariate. |
| [Lotfy], 1/1/2021, retrospective, Saudi Arabia, Middle East, peer-reviewed, mean age 55.0, 3 authors. | 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%). | |
| [Luo], 6/17/2020, retrospective, USA, North America, peer-reviewed, 31 authors. | risk of death, 2.2% higher, RR 1.02, p = 0.99, treatment 11 of 35 (31.4%), control 4 of 13 (30.8%), odds ratio converted to relative risk. |
| [Lyngbakken], 7/17/2020, Randomized Controlled Trial, Norway, Europe, peer-reviewed, median age 62.0, 11 authors. | 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. | |
| [López], 11/2/2020, retrospective, Spain, Europe, peer-reviewed, 7 authors. | 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%). |
| [Magagnoli], 4/21/2020, retrospective, database analysis, USA, North America, peer-reviewed, 7 authors. | 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 per study, 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 per study, 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 per study, 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 per study, HCQ. | |
| [Mahévas], 5/14/2020, retrospective, France, Europe, peer-reviewed, 34 authors. | 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 per study. |
| [Maldonado], 11/5/2020, retrospective, Spain, Europe, peer-reviewed, 10 authors. | risk of death, 90.9% lower, RR 0.09, p = 0.17, treatment 1 of 11 (9.1%), control 1 of 1 (100.0%). |
| [Mallat], 5/2/2020, retrospective, Abu Dhabi, Middle East, peer-reviewed, 8 authors. | time to viral-, 203.0% higher, relative time 3.03, p = 0.02, treatment 23, control 11. |
| [Martin-Vicente], 3/8/2021, retrospective, Spain, Europe, preprint, 38 authors. | risk of death, 59.3% lower, RR 0.41, p = 0.41, treatment 37 of 91 (40.7%), control 1 of 1 (100.0%). |
| [Martinez-Lopez], 6/30/2020, retrospective, Spain, Europe, peer-reviewed, median age 71.0, 25 authors. | risk of death, 33.0% lower, RR 0.67, p = 0.20, treatment 47 of 148 (31.8%), control 9 of 19 (47.4%). |
| [Matangila], 12/18/2020, retrospective, DR Congo, Africa, peer-reviewed, median age 54.0, 12 authors. | 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 per study, odds ratio converted to relative risk. |
| [McGrail], 7/19/2020, retrospective, USA, North America, preprint, 2 authors. | risk of death, 70.0% higher, RR 1.70, p = 0.69, treatment 4 of 33 (12.1%), control 3 of 42 (7.1%). |
| [Membrillo de Novales], 5/5/2020, retrospective, Spain, Europe, preprint, 19 authors. | risk of death, 55.1% lower, RR 0.45, p = 0.002, treatment 27 of 123 (22.0%), control 21 of 43 (48.8%). |
| [Mikami], 6/30/2020, retrospective, USA, North America, peer-reviewed, 7 authors. | 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 per study. |
| [Modrák], 12/4/2020, retrospective, Czech Republic, Europe, preprint, 26 authors. | risk of death, 59.0% lower, RR 0.41, p = 0.04, treatment 108, control 105, Cox (single). |
| [Nachega], 10/2/2020, retrospective, database analysis, Democratic Republic of Congo, Africa, peer-reviewed, median age 46.0, 25 authors. | 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 per study, odds ratio converted to relative risk. |
| risk of no improvement, 25.8% lower, RR 0.74, p = 0.13, adjusted per study, odds ratio converted to relative risk. | |
| [Naseem], 12/14/2020, retrospective, Pakistan, South Asia, preprint, 5 authors. | risk of death, 33.3% lower, RR 0.67, p = 0.34, treatment 77, control 1137, multivariate Cox. |
| [Núñez-Gil], 11/9/2020, retrospective, database analysis, multiple countries, Europe, peer-reviewed, median age 68.0, 49 authors. | 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 per study, odds ratio converted to relative risk. |
| [Orioli], 12/14/2020, retrospective, Belgium, Europe, peer-reviewed, 9 authors. | risk of death, 12.7% lower, RR 0.87, p = 1.00, treatment 8 of 55 (14.5%), control 3 of 18 (16.7%). |
| [Ouedraogo], 2/5/2021, retrospective, Burkina Faso, Africa, peer-reviewed, 14 authors. | 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. | |
| [Ozturk], 12/4/2020, retrospective, Turkey, Middle East, peer-reviewed, 70 authors. | 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. |
| [Paccoud], 6/18/2020, retrospective, France, Europe, peer-reviewed, 20 authors. | 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 per study. |
| [Pasquini], 8/23/2020, retrospective, Italy, Europe, peer-reviewed, 9 authors | risk of death, 16.4% lower, RR 0.84, p = 0.34, treatment 23 of 33 (69.7%), control 15 of 18 (83.3%). |
| [Peng], 12/4/2020, retrospective, China, Asia, peer-reviewed, 21 authors. | 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 of AKI. |
| [Peters], 8/15/2020, retrospective, Netherlands, Europe, peer-reviewed, 21 authors | 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 per study. |
| [Pinato], 8/18/2020, retrospective, multiple countries, Europe, peer-reviewed, 64 authors. | risk of death, 59.0% lower, RR 0.41, p < 0.001, treatment 30 of 182 (16.5%), control 181 of 446 (40.6%). |
| [Psevdos], 12/31/2020, retrospective, USA, North America, peer-reviewed, 3 authors. | America, peer-reviewed, 3 authors. Submit Corrections or Updates. risk of death, 63.5% higher, RR 1.63, p = 0.52, treatment 17 of 52 (32.7%), control 3 of 15 (20.0%). |
| [Purwati], 2/9/2021, Double Blind Randomized Controlled Trial, Indonesia, Asia, peer-reviewed, 12 authors. | 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%). |
| [Qin], 11/23/2020, retrospective, China, Asia, peer-reviewed, 17 authors. | risk of death, 34.3% lower, RR 0.66, p = 0.61, treatment 3 of 43 (7.0%), control 75 of 706 (10.6%). |
| [RECOVERY], 6/5/2020, Randomized Controlled Trial, United Kingdom, Europe, preprint, 29 authors | risk of death, 9.0% higher, RR 1.09, p = 0.15, treatment 421 of 1561 (27.0%), control 790 of 3155 (25.0%). |
| [Rivera], 7/22/2020, retrospective, USA, North America, peer-reviewed, 45 authors. | 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 per study, odds ratio converted to relative risk. |
| [Rivera-Izquierdo], 7/9/2020, retrospective, Spain, Europe, peer-reviewed, 21 authors | risk of death, 19.0% lower, RR 0.81, p = 0.75, treatment 215, control 23. |
| [Rodriguez], 11/9/2020, prospective, Spain, Europe, peer-reviewed, 13 authors. | 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-Gonzalez], 11/28/2020, retrospective, Spain, Europe, peer-reviewed, 20 authors | 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-Nava], 11/5/2020, retrospective, USA, North America, peer-reviewed, median age 68.0, 8 authors. | 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. |
| [Roig], 1/31/2021, retrospective, Spain, Europe, peer-reviewed, 6 authors. | risk of death, 15.6% lower, RR 0.84, p = 0.76, treatment 33 of 67 (49.3%), control 7 of 12 (58.3%). |
| [Roomi], 8/13/2020, retrospective, USA, North America, peer-reviewed, 11 authors. | 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 per study, odds ratio converted to relative risk. |
| [Rosenberg], 5/11/2020, retrospective, USA, North America, peer-reviewed, 14 authors. | 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 per study. |
| [Salazar], 11/4/2020, retrospective, USA, North America, peer-reviewed, 19 authors. | risk of death, 37.0% higher, RR 1.37, p = 0.28, treatment 12 of 92 (13.0%), control 80 of 811 (9.9%). |
| [Saleemi], 8/11/2020, retrospective, Saudi Arabia, Middle East, preprint, 5 authors | Middle East, preprint, 5 authors. Submit Corrections or Updates. median time to PCR-, 21.0% higher, relative time 1.21, p < 0.05, treatment 65, control 20. |
| [Salvador], 3/4/2021, prospective, Portugal, Europe, peer-reviewed, 10 authors. | risk of death, 32.9% lower, RR 0.67, p = 0.007, treatment 28 of 121 (23.1%), control 58 of 124 (46.8%), odds ratio converted to relative risk, 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%), odds ratio converted to relative risk, 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%), odds ratio converted to relative risk, univariate. | |
| [Sands], 1/1/2021, retrospective, database analysis, USA, North America, peer-reviewed, 10 authors. | risk of death, 69.9% higher, RR 1.70, p = 0.01, treatment 101 of 973 (10.4%), control 56 of 696 (8.0%), odds ratio converted to relative risk. |
| [Sarfaraz], 1/2/2021, retrospective, Pakistan, South Asia, preprint, 7 authors. | risk of death, 45.0% higher, RR 1.45, p = 0.07, treatment 40 of 94 (42.6%), control 27 of 92 (29.3%). |
| [Sbidian], 6/19/2020, retrospective, database analysis, France, Europe, preprint, 21 authors, whole population HCQ AIPTW adjusted. | 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 per study. |
| risk of no hospital discharge, 20.0% lower, RR 0.80, p = 0.002, adjusted per study. | |
| [Self], 11/9/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 33 authors | 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 per study, odds ratio converted to relative risk. |
| [Serrano], 9/22/2020, retrospective, Spain, Europe, peer-reviewed, 8 authors. | risk of death, 43.0% lower, RR 0.57, p = 0.14, treatment 6 of 14 (42.9%), control 6 of 8 (75.0%). |
| Shabrawishi], 5/11/2020, retrospective, Saudi Arabia, Middle East, preprint, mean age 43.9, 5 authors. | 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%). |
| [Sheshah], 11/13/2020, retrospective, Saudi Arabia, Middle East, peer-reviewed, 8 authors. | risk of death, 80.0% lower, RR 0.20, p < 0.001, treatment 267, control 33, odds ratio converted to relative risk. |
| [Shoaibi], 9/24/2020, retrospective, database analysis, USA, North America, preprint, 5 authors. | risk of death, 15.4% lower, RR 0.85, p < 0.001, treatment 686 of 5047 (13.6%), control 3923 of 24404 (16.1%). |
| [Signes-Costa], 12/16/2020, retrospective, Spain, Canada, China, Cuba, Ecuador, Germany, Italy, Europe, Asia, Caribbean, North America, South America, peer-reviewed, 28 authors. | risk of death, 47.0% lower, RR 0.53, p < 0.001, treatment 4854, control 993, adjusted per study. |
| [Singh], 5/19/2020, retrospective, database analysis, USA, North America, preprint, 4 author | 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%). | |
| [Solh], 10/20/2020, retrospective, database analysis, USA, North America, preprint, 5 authors. | 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 per study. |
| [SOLIDARITY], 10/15/2020, Randomized Controlled Trial, multiple countries, multiple regions, peer-reviewed, baseline oxygen requirements 64.0%, 15 authors. | risk of death, 19.0% higher, RR 1.19, p = 0.23, treatment 104 of 947 (11.0%), control 84 of 906 (9.3%). |
| [Sosa-García], 6/29/2020, retrospective, Mexico, North America, peer-reviewed, baseline oxygen requirements 100.0%, 6 authors. | risk of death, 10.5% higher, RR 1.11, p = 1.00, treatment 7 of 38 (18.4%), control 3 of 18 (16.7%). |
| [Soto-Becerra], 10/8/2020, retrospective, database analysis, Peru, South America, preprint, median age 59.4, 4 authors. | 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 per study, day 30. | |
| [Stewart], 3/17/2021, retrospective, USA, North America, peer-reviewed, 37 authors. | 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 per study, 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 per study, 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 per study, 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 per study, 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 per study, 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 per study, Aetion, HCQ. | |
| [Stewart (B)], 3/17/2021, retrospective, USA, North America, peer-reviewed, 37 authors. | 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 per study, Aetion, HCQ. |
| [Stewart (C)], 3/17/2021, retrospective, USA, North America, peer-reviewed, 37 authors | 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 per study, 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 per study, Aetion, HCQ. | |
| [Stewart (D)], 3/17/2021, retrospective, USA, North America, peer-reviewed, 37 authors. | 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 per study, 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 per study, 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 per study, Aetion, HCQ. | |
| [Stewart (E)], 3/17/2021, retrospective, USA, North America, peer-reviewed, 37 authors. | 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 per study, 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 per study, 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 per study, 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 per study, Aetion, HCQ. | |
| [Stewart (F)], 3/17/2021, retrospective, USA, North America, peer-reviewed, 37 authors | 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 per study, 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 per study, 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 per study, 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 per study, Aetion, HCQ. | |
| [Stewart (G)], 3/17/2021, retrospective, USA, North America, peer-reviewed, 37 authors. | 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 per study, 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 per study, 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 per study, 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 per study, 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 per study, Aetion, HCQ. | |
| [Synolaki], 9/5/2020, retrospective, Greece, Europe, preprint, 20 authors. | risk of death, 23.6% lower, RR 0.76, p = 0.27, treatment 21 of 98 (21.4%), control 60 of 214 (28.0%). |
| [Sánchez-Álvarez], 4/27/2020, retrospective, database analysis, Spain, Europe, peer-reviewed, mean age 67.0, 10 authors | risk of death, 45.9% lower, RR 0.54, p = 0.005, treatment 322, control 53, odds ratio converted to relative risk. |
| [Taccone], 12/23/2020, retrospective, Belgium, Europe, peer-reviewed, 10 authors | risk of death, 24.7% lower, RR 0.75, p < 0.001, treatment 449 of 1308 (34.3%), control 183 of 439 (41.7%), odds ratio converted to relative risk. |
| [Tan], 12/14/2020, retrospective, China, Asia, peer-reviewed, 7 authors. | hospitalization time, 35.2% lower, relative time 0.65, p = 0.04, treatment 8, control 277. |
| [Tang], 4/14/2020, Randomized Controlled Trial, China, Asia, peer-reviewed, 24 authors. | 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%). |
| [Tehrani], 10/30/2020, retrospective, Sweden, Europe, peer-reviewed, 5 authors. | risk of death, 13.4% lower, RR 0.87, p = 0.63, treatment 16 of 65 (24.6%), control 54 of 190 (28.4%). |
| [Texeira], 12/31/2020, retrospective, USA, North America, peer-reviewed, 6 authors. | risk of death, 79.3% higher, RR 1.79, p = 0.10, treatment 17 of 65 (26.2%), control 14 of 96 (14.6%). |
| [Trullàs], 7/14/2020, retrospective, Spain, Europe, preprint, median age 75.0, 8 authors. | risk of death, 35.6% lower, RR 0.64, p = 0.12, treatment 20 of 66 (30.3%), control 16 of 34 (47.1%). |
| [Ubaldo], 2/1/2021, retrospective, Philippines, Asia, peer-reviewed, 3 authors. | 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. |
| [Ulrich], 9/23/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, baseline oxygen requirements 63.3%, mean age 66.2, 18 authors. | risk of death, 6.0% higher, RR 1.06, p = 1.00, treatment 7 of 67 (10.4%), control 6 of 61 (9.8%). |
| [van Halem], 11/27/2020, retrospective, Belgium, Europe, peer-reviewed, 10 authors. | risk of death, 31.6% lower, RR 0.68, p = 0.05, treatment 34 of 164 (20.7%), control 47 of 155 (30.3%). |
| [Vernaz], 12/31/2020, retrospective, Switzerland, Europe, peer-reviewed, 15 authors. | 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. | |
| Wang], 6/10/2020, retrospective, database analysis, USA, North America, peer-reviewed, 3 authors. | risk of death, 5.8% lower, RR 0.94, p = 0.63, treatment 1866, control 5726, odds ratio converted to relative risk. |
| [Xia], 2/11/2020, retrospective, China, Asia, preprint, 1 author. | 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%). |
| [Yegerov], 1/8/2021, retrospective, Kazakhstan, Asia, peer-reviewed, 8 authors. | 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 zero event (with reciprocal of the contrasting arm). |
| [Yu (B)], 8/3/2020, retrospective, China, Asia, preprint, median age 62.0, 6 authors | 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 (C)], 5/15/2020, retrospective, China, Asia, peer-reviewed, 8 authors. | risk of death, 60.5% lower, RR 0.40, p = 0.002, treatment 9 of 48 (18.8%), control 238 of 502 (47.4%). |
| [Zhong], 3/26/2020, retrospective, China, Asia, preprint, 1 author. | 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 per study. |
| [Águila-Gordo], 11/11/2020, retrospective, Spain, Europe, peer-reviewed, mean age 84.4, 6 authors. | 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 per study. |
| [Ñamendys-Silva], 10/21/2020, retrospective, database analysis, Mexico, North America, peer-reviewed, mean age 57.3, 18 authors. | 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. |
Pre‑Exposure Prophylaxis
Effect extraction follows pre-specified rules as detailed above and gives priority to more serious outcomes. Only the first (most serious) outcome is used in calculations, which may differ from the effect a paper focuses on.
| [Abella], 9/30/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 18 authors. | 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%). |
| [Alegiani], 4/15/2021, retrospective, database analysis, Italy, Europe, peer-reviewed, 16 authors. | 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. | |
| [Alzahrani], 4/15/2021, retrospective, Saudi Arabia, Middle East, peer-reviewed, 3 authors. | 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 zero event (with reciprocal of the contrasting arm). |
| 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 (with reciprocal of the contrasting arm). | |
| 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%). | |
| [Arleo], 10/27/2020, retrospective, USA, North America, preprint, 5 authors. | 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. | |
| [Bae], 2/20/2021, retrospective, South Korea, Asia, peer-reviewed, 8 authors. | 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%), odds ratio converted to relative risk, 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%), odds ratio converted to relative risk, 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%), odds ratio converted to relative risk, PSM, adjusted for immunosuppresant use. | |
| risk of COVID-19 case, 40.2% lower, RR 0.60, p = 0.08, odds ratio converted to relative risk, PSM, HCQ >= 6 months. | |
| [Behera], 11/3/2020, retrospective, India, South Asia, peer-reviewed, 13 authors. | 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 per study, odds ratio converted to relative risk, 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%), odds ratio converted to relative risk, matched pair analysis. | |
| [Bhattacharya], 6/9/2020, retrospective, India, South Asia, preprint, 7 authors. | 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%). |
| [Cassione], 5/12/2020, retrospective, Italy, Europe, preprint, survey, median age 52.5, 6 authors. | 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%). |
| [Chatterjee], 5/28/2020, retrospective, India, South Asia, peer-reviewed, survey, 11 authors. | 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 |
| [Cordtz], 12/28/2020, retrospective, Denmark, Europe, peer-reviewed, 10 authors. | 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 per study, time-dependent exposure 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 per study, time-fixed exposure model. | |
| [de la Iglesia], 9/2/2020, retrospective, database analysis, Spain, Europe, preprint, 17 authors. | 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. | |
| [Desbois], 7/20/2020, retrospective, France, Europe, preprint, mean age 58.8, 13 authors. | 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%). |
| [Dev], 3/24/2021, retrospective, India, South Asia, peer-reviewed, 5 authors. | 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. |
| [Ferreira], 6/29/2020, retrospective, database analysis, Portugal, Europe, peer-reviewed, 3 authors. | risk of COVID-19 case, 47.1% lower, RR 0.53, p < 0.001, adjusted per study, odds ratio converted to relative risk. |
| [Ferri], 8/27/2020, retrospective, Italy, Europe, peer-reviewed, survey, 29 authors. | 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%). |
| [Fitzgerald], 2/5/2021, retrospective, USA, North America, preprint, 34 authors. | 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 per study, odds ratio converted to relative risk |
| [Gendebien], 6/25/2020, retrospective, Belgium, Europe, preprint, survey, 9 authors. | 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%). |
| Gendelman], 5/5/2020, retrospective, database analysis, Israel, Middle East, peer-reviewed, 5 authors. | 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%). |
| [Gentry], 9/21/2020, retrospective, database analysis, USA, North America, peer-reviewed, 6 authors. | 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 (with reciprocal of the contrasting arm), 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 (with reciprocal of the contrasting arm), 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%), odds ratio converted to relative risk. | |
| [Gianfrancesco], 5/28/2020, retrospective, database analysis, multiple countries, multiple regions, peer-reviewed, 28 authors. | risk of hospitalization, 3.3% lower, RR 0.97, p = 0.82, treatment 58 of 130 (44.6%), control 219 of 470 (46.6%), odds ratio converted to relative risk. |
| [Goenka], 10/24/2020, retrospective, India, South Asia, preprint, 11 authors. | 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 per study, odds ratio converted to relative risk. |
| [Grau-Pujol], 9/21/2020, Randomized Controlled Trial, Spain, Europe, preprint, 22 authors. | 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 to zero event (with reciprocal of the contrasting arm). |
| [Gönenli], 12/16/2020, retrospective, Turkey, Middle East, preprint, survey, 4 authors. | 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%), odds ratio converted to relative risk. | |
| [Huang], 6/16/2020, retrospective, China, Asia, peer-reviewed, 15 authors. | risk of hospitalization, 80.0% lower, RR 0.20, p < 0.001, treatment 8, control 1247. |
| [Huh], 12/19/2020, retrospective, database analysis, South Korea, Asia, peer-reviewed, 8 authors. | 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 per study. |
| 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 per study. | |
| [Huh (B)], 5/4/2020, retrospective, database analysis, South Korea, Asia, preprint, 10 authors. | risk of COVID-19 case, 47.7% higher, RR 1.48, p = 0.09, odds ratio converted to relative risk. |
| [Jung], 12/11/2020, retrospective, South Korea, Asia, peer-reviewed, 6 authors. | 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 zero event (with reciprocal of the contrasting arm). |
| 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 per study. | |
| [Khurana], 7/24/2020, retrospective, India, South Asia, preprint, survey, 5 authors. | 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%), odds ratio converted to relative risk. |
| [Konig], 5/7/2020, retrospective, database analysis, multiple countries, multiple regions, preprint, 11 authors. | risk of hospitalization, 3.0% lower, RR 0.97, p = 0.88, treatment 16 of 29 (55.2%), control 29 of 51 (56.9%). |
| [Laplana], 9/9/2020, retrospective, Spain, Europe, peer-reviewed, survey, 3 authors. | 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%). |
| [Macias], 5/16/2020, retrospective, database analysis, Spain, Europe, preprint, 12 authors. | 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%). | |
| [Mathai], 11/6/2020, retrospective, India, South Asia, peer-reviewed, 3 authors. | 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. | |
| [Mitchell], 5/5/2020, retrospective, multiple countries, multiple regions, preprint, 2 authors. | risk of death, 99.0% lower, RR 0.01, p < 0.001. |
| [Pham], 3/2/2021, retrospective, USA, North America, peer-reviewed, 5 authors. | risk of death, 19.7% lower, RR 0.80, p = 0.77, treatment 2 of 14 (14.3%), control 5 of 28 (17.9%), odds ratio converted to relative risk, 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%), odds ratio converted to relative risk, univariate. | |
| [Rajasingham], 9/21/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 22 authors. | 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%). | |
| [Rangel], 1/10/2021, retrospective, USA, North America, peer-reviewed, 5 authors. | 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. | |
| [Rentsch], 9/9/2020, retrospective, database analysis, United Kingdom, Europe, peer-reviewed, 34 authors. | risk of death, 3.0% higher, RR 1.03, p = 0.83, adjusted per study. |
| [Revollo], 11/21/2020, retrospective, Spain, Europe, peer-reviewed, 16 authors. | 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 per study, 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 per study, PSM risk of IgG+. | |
| [Salvarani], 8/6/2020, retrospective, Italy, Europe, peer-reviewed, 18 authors. | reviewed, 18 authors. Submit Corrections or Updates. risk of COVID-19 case, 6.0% lower, RR 0.94, p = 0.75. |
| [Singer], 8/5/2020, retrospective, database analysis, USA, North America, preprint, 3 authors. | 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%). |
| [Trefond], 1/27/2021, retrospective, France, Europe, preprint, 21 authors. | 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 per study, odds ratio converted to relative risk. |
| 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 per study, odds ratio converted to relative risk. | |
| 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 per study, odds ratio converted to relative risk. | |
| [Vivanco-Hidalgo], 3/9/2021, retrospective, Spain, Europe, peer-reviewed, 8 authors. | 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 per study. |
| 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 per study. | |
| [Zhong (B)], 7/3/2020, retrospective, database analysis, China, Asia, peer-reviewed, 20 authors. | 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 per study. |
Post‑Exposure Prophylaxis
Effect extraction follows pre-specified rules as detailed above and gives priority to more serious outcomes. Only the first (most serious) outcome is used in calculations, which may differ from the effect a paper focuses on.
| [Barnabas], 12/7/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 30 authors. | 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 per study, 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 per study, 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 per study, 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 per study, day 14 PCR+ mITT IDWeek. | |
| 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 per study, day 14 PCR+ ITT AIM. | |
| [Boulware (B)], 6/3/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 24 authors. | 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. | |
| [Dhibar], 11/6/2020, prospective, India, South Asia, peer-reviewed, 13 authors. | 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 per study. |
| 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 per study, 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 per study. | |
| [Mitjà (B)], 7/26/2020, Randomized Controlled Trial, Spain, Europe, peer-reviewed, 12 authors | 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 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%). | |
| [Polat], 9/30/2020, prospective, Turkey, Middle East, peer-reviewed, 3 authors. | 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%). |
| [Seet], 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. | 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 per study, odds ratio converted to relative risk, model 6. | |
| [Simova (B)], 11/12/2020, retrospective, Bulgaria, Europe, peer-reviewed, 5 authors. | 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 to zero event (with reciprocal of the contrasting arm). |
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