https://hcqmeta.com/
•32 of the
33 early
treatment studies report a positive effect.
19 show statistically significant
improvements in isolation (14 for the
most serious outcome).
•46 of the 60 pre-exposure prophylaxis studies report a positive
effect.
18 show statistically significant
improvements in isolation (16 for the most
serious outcome).
12 of
the 14 negative
effects are from studies where all or most patients were autoimmune
disorder patients.
•Late treatment is less successful,
with only 67% of the
203 studies reporting a positive effect. Very
late stage treatment is not effective and may be harmful, especially when
using excessive dosages.
•84% of Randomized Controlled Trials (RCTs) for
early, PrEP, or PEP treatment report positive effects, the probability of results
as good or better for an ineffective treatment is
0.0022.
•Meta analysis using the most serious
outcome reported shows 64% [54‑72%] improvement for the
33 early
treatment studies. Results are similar after exclusion based sensitivity
analysis and after restriction to
peer-reviewed studies. Restricting to the 8 RCTs shows 46% [16‑65%] improvement,
and restricting to the 13
mortality results
shows 75% [60‑84%] lower mortality.
•There is evidence of bias towards publishing negative results.
77% of prospective studies report positive
effects, compared to 71% of retrospective
studies. Studies from North America
are 2.7
times more likely to report negative results than studies from the rest of the
world combined, p = 0.0000000264. The probability that an
ineffective treatment generated results as positive as the 303
studies is estimated to be 1 in 1 quadrillion.
•Negative meta analyses of HCQ generally choose a subset
of trials, focusing on late treatment, especially trials with very late
treatment and excessive dosages.
•While many treatments have some level
of efficacy, they do not replace vaccines and other measures to avoid
infection. Only 5% of HCQ studies
show zero events in the treatment arm.
•Elimination of COVID-19 is a race
against viral evolution. No treatment, vaccine, or intervention is 100%
available and effective for all current and future variants. All practical,
effective, and safe means should be used. Not doing so increases the risk of
COVID-19 becoming endemic; and increases mortality, morbidity, and collateral
damage.
•All data to reproduce this paper and
the sources are in the appendix.
See [Ladapo, Prodromos, Risch, Risch (B)] for other meta analyses
showing efficacy when HCQ is used early.
 |
| Total | 303 studies | 4,815 authors | 415,929 patients |
| Positive effects | 220 studies | 3,411 authors | 293,403 patients |
| Early treatment | 64% improvement | RR 0.36 [0.28-0.46] |
| Late treatment | 19% improvement | RR 0.81 [0.76-0.86] |
Figure 1. A. Random effects
meta-analysis of all early treatment studies. This plot shows pooled effects, analysis for individual outcomes is below, and
more details on pooled effects can be found in the heterogeneity section.
Effect extraction is pre-specified, using the most serious outcome reported.
Simplified dosages are shown for comparison, these are the total dose in the
first four days. Chloroquine is indicated with (c). For details of
effect extraction and full dosage information see the appendix.
B. Scatter plot of the effects reported in early treatment studies and
in all studies. Early treatment is more effective. C and D.
Chronological history of all reported effects, with the probability that the
observed or greater frequency of positive results were generated by an
ineffective treatment.
Introduction
We analyze all significant studies concerning the use of HCQ
(or CQ) for COVID-19. Search methods, inclusion criteria, effect extraction
criteria (more serious outcomes have priority), all individual study data,
PRISMA answers, and statistical methods are detailed in Appendix 1. We
present random-effects meta-analysis results for all studies, for studies
within each treatment stage, for mortality results only, after exclusion of
studies with critical bias, and for Randomized Controlled Trials (RCTs) only.
Typical meta analyses involve subjective selection criteria and bias
evaluation, requiring an understanding of the criteria and the accuracy of the
evaluations. However, the volume of studies presents an opportunity for an
additional simple and transparent analysis aimed at detecting efficacy.
If treatment was not effective, the observed effects would be
randomly distributed (or more likely to be negative if treatment is harmful).
We can compute the probability that the observed percentage of positive
results (or higher) could occur due to chance with an ineffective treatment
(the probability of >= k heads in n coin tosses, or the
one-sided sign test / binomial test). Analysis of publication bias is
important and adjustments may be needed if there is a bias toward publishing
positive results. For HCQ, we find evidence of a bias toward publishing
negative results.
Figure 2 shows stages of possible treatment for
COVID-19. Pre-Exposure Prophylaxis (PrEP) refers to regularly taking
medication before being infected, in order to prevent or minimize infection.
In Post-Exposure Prophylaxis (PEP), medication is taken after exposure
but before symptoms appear. Early Treatment refers to treatment
immediately or soon after symptoms appear, while Late Treatment refers
to more delayed treatment.
Figure 2. Treatment stages.
Results
Figure 3, Figure 4, and
Table 1 show results by treatment stage, and Figure 5
shows a forest plot for a random effects meta-analysis of all studies.
Figure 6 and Figure 7 show forest plots restricted to mortality
and hospitalization results only.
Early treatment.
97% of early treatment studies
report a positive effect, with an estimated reduction of
64% in the effect measured
(death, hospitalization, etc.) from the random effects meta-analysis, RR
0.36
[0.28-0.46].Late treatment.
Late treatment studies are
mixed, with 67% showing positive
effects, and an estimated reduction of
19% in the random effects
meta-analysis. Negative studies mostly fall into the following categories:
they show evidence of significant unadjusted confounding, including
confounding by indication; usage is extremely late; or they use an excessively
high dosage.Pre-Exposure Prophylaxis.
77% of PrEP studies show positive
effects, with an estimated reduction of
32% in the random effects
meta-analysis. Negative studies are all studies of systemic autoimmune disease
patients which either do not adjust for the different baseline risk of these
patients at all, or do not adjust for the highly variable risk within these
patients.Post-Exposure Prophylaxis.
88% of PEP studies report positive
effects, with an estimated reduction of
33% in the random effects
meta-analysis.| Treatment 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 | 32 | 33 | 97.0% | 1 in 253 million |
64% improvement RR 0.36 [0.28‑0.46] p < 0.0001 |
| Late treatment | 137 | 204 | 67.2% | 1 in 2 million |
19% improvement RR 0.81 [0.76‑0.86] p < 0.0001 |
| Pre‑Exposure Prophylaxis | 47 | 61 | 77.0% | 1 in 74 thousand |
32% improvement RR 0.68 [0.56‑0.81] p < 0.0001 |
| Post‑Exposure Prophylaxis | 7 | 8 | 87.5% | 1 in 28 |
33% improvement RR 0.67 [0.53‑0.83] p = 0.00043 |
| All studies | 220 | 303 | 72.6% | 1 in 1 quadrillion |
25% improvement RR 0.75 [0.71‑0.79] p < 0.0001 |
Table 1. Results by treatment stage.
3 studies report results for a subset with early
treatment, these are not included in the overall results.
Figure 3. Results by treatment stage.
Figure 4. Chronological history of results by
treatment stage, with the probability that the observed or greater frequency
of positive results were generated by an ineffective treatment.
Figure 5. Random effects meta-analysis. This plot shows pooled effects, analysis for individual outcomes is below, and
more details on pooled effects can be found in the heterogeneity section.
Effect extraction is pre-specified, using the most serious outcome reported,
see the appendix for details.
(ES) indicates the early treatment subset of a study (these are not included
in the overall results).
Figure 6. Random effects meta-analysis for
mortality results only. (ES) indicates the early treatment subset of a study
(these are not included in the overall results).
Figure 7. Random effects meta-analysis for
hospitalization results only.
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 8, Figure 9, 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
28%
improvement in random effects meta-analysis, RR
0.72
[0.60‑0.87],
p = 0.00062. Early treatment RCTs show
46% improvement,
RR 0.54
[0.35‑0.84],
p = 0.0058.
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].
Figure 8. Randomized Controlled Trials. Effect extraction is pre-specified, using the most serious outcome reported,
see the appendix for details.
A. Scatter plot of all effects comparing RCTs to non-RCTs. B. Chronological history of all reported effects.
| 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 | 33 | 47 | 70.2% | 1 in 252 |
20% improvement RR 0.80 [0.67‑0.94] p = 0.0084 |
| Randomized Controlled Trials (excluding late treatment) | 16 | 19 | 84.2% | 1 in 452 |
28% improvement RR 0.72 [0.60‑0.87] p = 0.00062 |
Table 2. Summary of RCT results.
Analysis with Exclusions
Many 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 10.
[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 stages of the pandemic when overall treatment protocols improved dramatically.
[Alghamdi], unadjusted results with no group details, very late stage, ICU patients.
[Alghamdi (B)], confounding by indication is likely and adjustments do not consider COVID-19 severity.
[Alhamlan], substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
[Annie], confounding by indication is likely and adjustments do not consider COVID-19 severity.
[Aparisi], unadjusted results with no group details.
[Awad], substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely.
[Barbosa], excessive unadjusted differences between groups.
[Barra], unadjusted results with no group details.
[Bielza], unadjusted results with no group details.
[Boari], unadjusted results with no group details.
[Bosaeed], very late stage, >50% on oxygen/ventilation at baseline.
[Budhiraja], excessive unadjusted differences between groups.
[Cassione], not fully adjusting for the different baseline risk of systemic autoimmune patients.
[Chari], unadjusted results with no group details.
[Chechter], unadjusted results with no group details.
[Choi], excessive unadjusted differences between groups.
[Coll], unadjusted results with no group details.
[Cravedi], substantial unadjusted confounding by indication likely.
[de la Iglesia], not fully adjusting for the different baseline risk of systemic autoimmune patients.
[De Luna], unadjusted results with no group details, substantial unadjusted confounding by indication likely.
[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.
[Fung], not fully adjusting for the different baseline risk of systemic autoimmune patients.
[Gadhiya], substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, 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.
[Goldman], unadjusted results with no group details.
[Gupta], very late stage, >50% on oxygen/ventilation at baseline.
[Hraiech], very late stage, ICU patients.
[Huang], significant unadjusted confounding possible.
[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.
[Jacobs], unadjusted results with no group details, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
[Kamran], excessive unadjusted differences between groups.
[Kamstrup], not fully adjusting for the different baseline risk of systemic autoimmune patients.
[Kelly], substantial unadjusted confounding by indication likely.
[Konig], not fully adjusting for the baseline risk differences within systemic autoimmune patients.
[Krishnan], unadjusted results with no group details.
[Kuderer], substantial unadjusted confounding by indication likely.
[Küçükakkaş], minimal details of groups provided.
[Lamback], substantial time varying confounding likely due to declining usage over the early stages of the pandemic 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 stages of the pandemic when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely.
[Luo], substantial unadjusted confounding by indication likely.
[Macias], not fully adjusting for the baseline risk differences within systemic autoimmune patients.
[Maldonado], treatment or control group size extremely small.
[Martin-Vicente], unadjusted results with no group details, treatment or control group size extremely small.
[McGrail], excessive unadjusted differences between groups.
[Menardi], excessive unadjusted differences between groups, substantial unadjusted confounding by indication likely.
[Mitchell], excessive unadjusted differences between groups.
[Mohandas], substantial unadjusted confounding by indication likely, unadjusted results with no group details, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
[Mulhem], substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
[Pasquini], unadjusted results with no group details.
[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 stages of the pandemic when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely.
[Qin], unadjusted results with no group details.
[Ramírez-García], excessive unadjusted differences between groups, substantial unadjusted confounding by indication likely.
[Rangel], not fully adjusting for the different baseline risk of systemic autoimmune patients.
[Rao], unadjusted results with minimal group details.
[RECOVERY], excessive dosage in late stage patients, 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], unadjusted results with no group details.
[Rodriguez-Nava], substantial unadjusted confounding by indication likely, excessive unadjusted differences between groups, unadjusted results with no group details.
[Roger], substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
[Roig], unadjusted results with no group details.
[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.
[Saib], substantial unadjusted confounding by indication likely.
[Salazar], substantial unadjusted confounding by indication likely, unadjusted results with no group details.
[Saleemi], substantial unadjusted confounding by indication likely.
[Salvarani], not fully adjusting for the different baseline risk of systemic autoimmune patients.
[Samajdar], minimal details provided, unadjusted results with no group details, results may be significantly affected by survey bias.
[Sammartino], substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
[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, unadjusted results with no group details.
[Sarhan], very late stage, >50% on oxygen/ventilation at baseline, significant unadjusted differences between groups.
[Sbidian], significant issues found with adjustments.
[Shoaibi], unadjusted results with no group details.
[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.
[Smith], immortal time bias may significantly affect results.
[Solh], very late stage, >50% on oxygen/ventilation at baseline, substantial unadjusted confounding by indication likely.
[SOLIDARITY], excessive dosage in late stage patients, 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 stages of the pandemic 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 stages of the pandemic 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 stages of the pandemic 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 stages of the pandemic 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 stages of the pandemic 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 stages of the pandemic 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 stages of the pandemic when overall treatment protocols improved dramatically, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons.
[Tehrani], substantial unadjusted confounding by indication likely, unadjusted results with no group details.
[Texeira], unadjusted results with no group details, no treatment details, substantial time varying confounding likely due to declining usage over the early stages of the pandemic 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, unadjusted results with no group details.
[Ulrich], very late stage, >50% on oxygen/ventilation at baseline.
[Vernaz], substantial time varying confounding likely due to declining usage over the early stages of the pandemic 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], minimal details provided.
[Yegerov], unadjusted results with no group details.
[Çivriz Bozdağ], substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
[Çiyiltepe], treatment group only includes patients where treatment failed resulting in ICU admission.
Figure 10. Random effects meta-analysis
excluding studies with significant issues. Effect extraction is pre-specified, using the most serious outcome reported,
see the appendix for details.
(ES) indicates the early treatment
subset of a study (these are not included in the overall results).
Heterogeneity
Heterogeneity in COVID-19 studies arises from many factors including:
Treatment delay.
The time between infection
or the onset of symptoms and treatment may critically affect how well a
treatment works. For example a medication may be very effective when used
early but may not be effective in late stage disease, and may even be harmful.
Figure 11 shows an example where efficacy declines as a
function of treatment delay. Other medications might be beneficial for late
stage complications, while early use may not be effective or may even be
harmful.
Figure 11. Effectiveness may depend critically on treatment delay.
Patient demographics.
Details of the
patient population including age and comorbidities may critically affect how
well a treatment works. For example, many COVID-19 studies with relatively
young low-comorbidity patients show all patients recovering quickly with or
without treatment. In such cases, there is little room for an effective
treatment to improve results.Effect measured.
Efficacy may differ
significantly depending on the effect measured, for example a treatment may be
very effective at reducing mortality, but less effective at minimizing cases
or hospitalization. Or a treatment may have no effect on viral clearance while
still being effective at reducing mortality.Variants.
There are thousands of
different variants of SARS-CoV-2 and efficacy may depend critically on the
distribution of variants encountered by the patients in a study.Regimen.
Effectiveness may depend
strongly on the dosage and treatment regimen.Treatments.
The use of other
treatments may significantly affect outcomes, including anything from other
medications, supplements, or other kinds of treatment such as prone
positioning.The distribution of studies will alter the outcome of a meta
analysis. Consider a simplified example where everything is equal except for
the treatment delay, and effectiveness decreases to zero or below with
increasing delay. If there are many studies using very late treatment, the
outcome may be negative, even though the treatment may be effective when used
earlier.
In general, by combining heterogeneous studies, as all meta
analyses do, we run the risk of obscuring an effect by including studies where
the treatment is less effective, not effective, or harmful.
When including studies where a treatment is less effective we
expect the estimated effect size to be lower than that for the optimal case.
We do not a priori expect that pooling all studies will create a
positive result for an effective treatment. Looking at all studies is valuable
for providing an overview of all research, and important to avoid
cherry-picking, but the resulting estimate does not apply to specific cases
such as early treatment in high-risk populations.
HCQ studies vary widely in all the factors above. We find a
significant effect based on treatment delay. Early treatment shows
consistently positive results, while late treatment results are very mixed.
Closer analysis may identify factors related to efficacy among this group, for
example treatment may be more effective in certain popuations, or more
fine-grained analysis of treatment delay may identify a point after which
treatment is ineffective.
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, 76.9% of prospective
studies report positive effects, compared to
71.1% of retrospective studies, suggesting a
bias toward publishing negative results. The median effect size for
prospective studies is 27% improvement,
compared to 24% for retrospective
studies. Figure 12 shows a scatter plot of results for prospective
and retrospective studies.
Figure 13 shows the results by region of the world, for
all regions that have > 5 studies. Studies from North America are
2.7 times more likely to report negative results
than studies from the rest of the world combined,
53.4% vs. 19.6%,
two-tailed z test -5.56, p =
0.0000000264. [Berry] performed an independent analysis
which also showed bias toward negative results for US-based research.
Figure 12. Prospective vs. retrospective studies.
Figure 14. Results by region.
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, Meeus, Meneguesso].
[Meeus], for example, report that their paper with 4,000 patients
reporting favourable outcomes for HCQ+AZ was rejected without peer review from
the editors of four different journals.
Although 220 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. 97% of early
treatment studies report a positive effect, with an estimated reduction of
64% in the effect measured
(death, hospitalization, etc.) in the random effects meta-analysis, RR
0.36
[0.28-0.46]. Negative Meta Analyses
Generally, it is easy to choose inclusion criteria and assign
biased risk evaluations in order to produce any desired outcome in a meta
analysis.
COVID-19 treatment studies have many sources of heterogeneity
which affect the results, including treatment delay (time from infection or
the onset of symptoms), patient population (age, comorbidities), the effect
measured and details of the measurement, distribution of SARS-CoV-2 variants,
dosage/regimen, and other treatments (anything from supplements, other
medications, or other kinds of treatment like prone positioning).
If a treatment is effective early, there is no reason to expect
it will also work late. Antivirals are typically only considered effective
when used within a short timeframe, for example 0-36 or 0-48 hours for
oseltamivir, with longer delays not being effective [McLean, Treanor].
For HCQ, the overwhelming majority of trials involve treatment not only after
48 hours but after 5 days - results from these trials are not relevant to
earlier usage.
Authors desiring to produce a negative outcome for HCQ need
only focus on late treatment studies. For example, [Axfors] assigns
89% weight to the RECOVERY and SOLIDARITY trials, producing the same negative
result. These trials used excessively high non-patient-customized dosage in
very sick late stage patients, dosages comparable to those known to be harmful
in that context [Borba]. The results are not generalizable to typical
dosage or treatment of earlier stage hospitalized patients, and certainly not
applicable to early treatment, i.e., at first glance we can see that this meta
analysis is of no relevance to early treatment.
This paper also does not appear to have been done very
carefully. For example, authors include [Borba] which is assigned 97%
weight for CQ. This study has no control group, comparing two different
dosages of CQ, which is clear from the abstract of the study.
[Axfors] approximate early treatment with outpatient
use, where they list 5 trials. This is misleading because authors ignore all
outcomes other than mortality, and only one of the 5 trials has mortality
events, so in reality only one trial is included. Table 1 shows the 5 trials,
only one with mortality. The text says something different: "among the five
studies on outpatients, there were three deaths, two occurring in the one
trial of 491 relatively young patients with few comorbidities and one
occurring in a small trial with 27 patients". We do not know what the missing
27 patient trial is, none of the 5 outpatient trials in Table 1 show 27
patients. There is an outpatient trial with 27 patients [Amaravadi],
however that trial reports no mortality. It does appear in the meta analysis,
but is reported as being an inpatient trial with zero mortality (in reality it
was a remotely conducted trial of patients quarantined at home). The
supplementary appendix has another different version for outpatient trials,
with only 4 trials in Table S3 and Figure S2B (only one with mortality).
Therefore, of the 33 early
treatment trials, authors have included data from only one, which contains
only 1 death in each of the treatment and control groups. If we read the
actual study [Skipper], we find that the death in the treatment group
was a non-hospitalized patient, suggesting that the death was not caused by
COVID-19, or at a minimum the patient did not receive standard care and the
comparison here is therefore not valid.
Conclusion
HCQ is an effective treatment for COVID-19. Treatment is more
effective when used early. Meta analysis using the most serious outcome reported shows 64% [54‑72%] improvement for the 33 early treatment studies. Results are
similar after exclusion based sensitivity analysis and after restriction to
peer-reviewed studies. Restricting to the 8 RCTs
shows 46% [16‑65%] improvement, and restricting to the 13 mortality
results shows 75% [60‑84%] lower mortality.
Very late stage treatment is not effective and may
be harmful, especially when using excessive dosages.
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 https://hcqmeta.com/.
12/23: We added [McKinnon].
12/14: We noted that the majority of the PrEP studies reporting
negative effects are studies where all or most patients were autoimmune
disorder patients [Crawford].
12/12: We added [Rao].
12/11: We added [Calderón].
12/5: We added [Ferreira].
12/4: We added [Ahmed].
12/4: We updated [Grau-Pujol] to the journal version.
11/18: We added [Samajdar].
11/7: We added [Chechter].
11/3: We added [Guglielmetti (B), Sarhan].
10/19: We added a summary plot for all results.
10/12: We added [Menardi].
10/10: We added [Luo (B)].
10/4: We added [Fung].
10/4: We added [Babalola].
9/29: We corrected a display error causing some points to be missing in Figure 3.
9/19: We added [Alotaibi, Çivriz Bozdağ].
9/17: We added [Çiyiltepe].
9/15: We added [Agarwal].
9/14: We added [Sawanpanyalert].
9/14: We added [Mulhem].
9/12: We added [Küçükakkaş].
9/9: We added [Alhamlan].
9/7: Discussion updates.
8/28: We added [Patil].
8/27: We added [Rodrigues].
8/25: We added [Naggie].
8/21: We added [Gadhiya].
8/20: We corrected the event counts in [Berenguer].
8/17: We added [De Luna].
8/16: We added [Turrini].
8/12: We added [Shabani].
8/10: We added [Rogado].
8/8: We added [Di Castelnuovo].
8/6: We added [Yadav].
8/5: We added [Bhatt].
8/4: We added [Alghamdi].
8/3: We added [Barra].
7/19: We added analysis restricted to hospitalization results.
7/15: We added [Jacobs].
7/14: We added [Roger].
7/13: We added [Barrat-Due].
7/11: We added [Krishnan].
7/8: We updated [Cadegiani] to the journal version.
7/2: We added [Taieb].
6/22: We added [Schwartz].
6/21: We added [Ramírez-García].
6/16: We added [Saib].
6/12: We added [Sivapalan].
6/7: We added [Badyal].
6/6: We added [Lagier].
6/5: We added [Thompson].
6/4: We added [Byakika-Kibwika, Korkmaz].
5/28: We added [Million].
5/17: We added [Syed].
5/16: We added [Rojas-Serrano]. We corrected the group
sizes for [Skipper], and we excluded hospitalizations that were
reported as not being related to COVID-19.
5/15: We added [Sammartino].
5/14: We added more discussion of heterogeneity.
5/12: We added [De Rosa].
5/10: We added additional information in the abstract.
5/8: We added [Réa-Neto].
5/7: We added [Kokturk].
5/3: We added an explanation of how some meta analyses produce
negative results.
5/4: We added [Aghajani].
5/1: We added [Bosaeed].
4/29: We added [Mohandas].
4/23: We added [Reis].
4/14: We added [Seet].
4/9: We updated [Dubee] to the journal version.
4/6: We added [Mokhtari].
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.
4/2: We added [Salvarani].
4/1: We added [Alghamdi (B)].
3/29: We added [Barry].
3/28: We added [Stewart].
3/24: We added [Dev].
3/13: We added [Roy].
3/9: We added [Vivanco-Hidalgo].
3/8: We added [Martin-Vicente].
3/7: We added [Salvador].
3/5: We added [Lotfy].
3/3: We added [Pasquini].
3/2: We added [Pham].
2/28: We added [Rodriguez].
2/26: We added [Amaravadi].
2/23: We added [Gonzalez].
2/25: We added [Bae].
2/20: We added [Lamback].
2/18: We added [Awad].
2/17: We added [Purwati].
2/16: We added [Albani].
2/15: We added [Lora-Tamayo].
2/9: We added [Ouedraogo].
2/7: We added [Johnston].
2/6: We added [Fitzgerald].
2/5: We added [Hernandez-Cardenas].
2/2: We added [Bernabeu-Wittel].
2/1: We added [Trefond].
1/24: We added [Desbois, Psevdos]. We moved the analysis
with exclusions and mortality analysis to the main text.
1/21: We added [Li].
1/16: We added the effect measured for each study in the forest
plots.
1/15: We updated [Ip] to the published version.
1/12: We added [Li (B)].
1/11: We added [Rangel].
1/7: We added direct links to the study details in the
chronological plots.
1/6: We added direct links to the study details in the forest
plots.
1/5: We added [Sarfaraz].
1/4: We added [Vernaz].
1/3: We added dosage information for early treatment
studies.
1/2: We added the number of patients to the forest plots.
1/1/2021: We added [Sands].
12/31: We added additional details about the studies in the
appendix.
12/27: We added the total number of authors and patients.
12/25: We added [Chari].
12/24: We added [Su].
12/23: We added [Cangiano].
12/22: We added [Taccone].
12/21: We added [Matangila].
12/17: We added [Signes-Costa].
12/16: We added [Alqassieh, Naseem, Orioli, Sosa-García, Tan].
12/15: We added [Kalligeros, López].
12/14: We added [Rivera-Izquierdo, Rodriguez-Nava].
12/13: We added [Bielza].
12/11: We added [Jung].
12/9: We added [Agusti, Guglielmetti (B)].
12/8: We added [Barnabas].
12/7: We added [Maldonado].
12/2: We added [Rodriguez-Gonzalez].
12/1: We added [Capsoni].
11/30: We added [Abdulrahman].
11/28: We added [Lambermont].
11/27: We added [van Halem].
11/25: We added [Qin], and we added analysis
restricted to mortality results.
11/24: We added [Boari].
11/23: We added [Revollo].
11/20: We added [Omrani].
11/19: We added [Falcone].
11/18: We added [Budhiraja].
11/14: We added [Sheshah].
11/13: We added [Núñez-Gil, Águila-Gordo].
11/12: We added [Simova, Simova (B)].
11/10: We added [Mathai].
11/9: We added [Self].
11/8: We added [Dhibar].
11/1: We added [Trullàs].
10/31: We added [Frontera, Szente Fonseca, Tehrani].
10/30: We added [Berenguer, Faíco-Filho].
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).
10/22: 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.
10/21: 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.
10/20/2020: Initial revision.
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 a result 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 (the next most serious
outcome is used — no studies were excluded). For example, in low-risk
populations with no mortality, a reduction in mortality with treatment is not
possible, however a reduction in hospitalization, for example, is still
valuable.
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 (3.9.9)
with
scipy (1.7.3), pythonmeta (1.26), numpy (1.21.4), statsmodels (0.14.0), and plotly (5.4.0).
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 https://hcqmeta.com/.
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 pooled analysis, which may differ from the effect a paper
focuses on. Other outcomes are used in outcome specific analyses.
| [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 progression, 68.4% lower, RR 0.32, p = 0.21, treatment 2 of 87 (2.3%), control 4 of 55 (7.3%), NNT 20, pneumonia. |
| [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%), NNT 3.3. |
| 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%), NNT 3.7. |
| [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, peer-reviewed, 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%), NNT 68, relative risk is not 0 because of continuity correction due to zero events (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%), NNT 15, relative risk is not 0 because of continuity correction due to zero events (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%), NNT 5.1, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), control group 1. | |
| [Chechter], 11/5/2021, prospective, Brazil, South America, preprint, 13 authors, dosage 800mg day 1, 400mg days 2-5, excluded in exclusion analyses: unadjusted results with no group details. | risk of hospitalization, 94.7% lower, RR 0.05, p = 0.004, treatment 0 of 60 (0.0%), control 3 of 12 (25.0%), NNT 4.0, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm). |
| [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], 7/3/2020, retrospective, USA, North America, peer-reviewed, 3 authors, dosage 200mg bid days 1-5, this trial uses multiple treatments in the treatment arm (combined with zinc and azithromycin) - results of individual treatments may vary. | risk of death, 79.4% lower, RR 0.21, p = 0.12, treatment 1 of 141 (0.7%), control 13 of 377 (3.4%), NNT 37, 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%), NNT 8.0, 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%), NNT 29. |
| [Gautret], 3/17/2020, prospective, France, Europe, peer-reviewed, 18 authors, dosage 200mg tid days 1-10, excluded in exclusion analyses: excessive unadjusted differences between groups, results only for PCR status which may be significantly different to symptoms. | 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%), NNT 1.7. |
| [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%), NNT 4.4, 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%), NNT 34, relative risk is not 0 because of continuity correction due to zero events (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%), NNT 2.4, adjusted per study. |
| [Hong], 7/16/2020, retrospective, South Korea, Asia, peer-reviewed, 7 authors, dosage not specified. | risk of prolonged viral shedding, early vs. late HCQ, 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 (C)], 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%), NNT 2.0, relative risk is not 0 because of continuity correction due to zero events (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%), NNT 40. |
| 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%), NNT 81. | |
| risk of hospitalization, 37.3% lower, RR 0.63, p = 0.04, treatment 21 of 97 (21.6%), control 305 of 970 (31.4%), NNT 10, adjusted per study, odds ratio converted to relative risk. | |
| [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. |
| [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%), NNT 9.2, adjusted per study, odds ratio converted to relative risk. |
| [Million], 5/27/2021, retrospective, France, Europe, peer-reviewed, 28 authors, dosage 200mg tid days 1-10. | risk of death, 83.0% lower, RR 0.17, p < 0.001, treatment 5 of 8,315 (0.1%), control 11 of 2,114 (0.5%), NNT 217, adjusted per study. |
| risk of ICU admission, 44.0% lower, RR 0.56, p = 0.18, treatment 17 of 8,315 (0.2%), control 7 of 2,114 (0.3%), NNT 789, adjusted per study. | |
| risk of hospitalization, 4.0% lower, RR 0.96, p = 0.77, treatment 214 of 8,315 (2.6%), control 64 of 2,114 (3.0%), NNT 220, adjusted per study. | |
| [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%), NNT 89. |
| 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%), NNT 33. | |
| [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 7,295 (0.4%), control 287 of 21,464 (1.3%), NNT 103, adjusted per study, odds ratio converted to relative risk. |
| risk of hospitalization, 35.3% lower, RR 0.65, p < 0.001, treatment 523 of 7,295 (7.2%), control 2,382 of 21,464 (11.1%), NNT 25, 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%), NNT 304, 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%), NNT 94, 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. | |
| [Rodrigues], 8/25/2021, Double Blind Randomized Controlled Trial, Brazil, South America, peer-reviewed, 8 authors, dosage 400mg bid days 1-7. | risk of hospitalization, 200.0% higher, RR 3.00, p = 1.00, treatment 1 of 42 (2.4%), control 0 of 42 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm). |
| risk of no virological cure, 14.4% lower, RR 0.86, p = 0.15, treatment 29 of 36 (80.6%), control 32 of 34 (94.1%), NNT 7.4, PP, day 3. | |
| risk of no virological cure, 13.1% lower, RR 0.87, p = 0.45, treatment 23 of 36 (63.9%), control 25 of 34 (73.5%), NNT 10, PP, day 6. | |
| risk of no virological cure, 23.3% lower, RR 0.77, p = 0.47, treatment 13 of 36 (36.1%), control 16 of 34 (47.1%), NNT 9.1, PP, day 9. | |
| risk of no virological cure, 3.1% lower, RR 0.97, p = 1.00, treatment 31 of 42 (73.8%), control 32 of 42 (76.2%), NNT 42, ITT, day 3. | |
| risk of no virological cure, no change, RR 1.00, p = 1.00, treatment 25 of 42 (59.5%), control 25 of 42 (59.5%), ITT, day 6. | |
| risk of no virological cure, 6.2% lower, RR 0.94, p = 1.00, treatment 15 of 42 (35.7%), control 16 of 42 (38.1%), NNT 42, ITT, day 9. | |
| time to viral-, 8.8% lower, relative time 0.91, p = 0.26, treatment 36, control 34, PP. | |
| time to viral-, 1.4% lower, relative time 0.99, p = 0.85, treatment 42, control 42, ITT. | |
| [Roy], 3/12/2021, retrospective, database analysis, India, South Asia, preprint, 5 authors, dosage not specified, excluded in exclusion analyses: no serious outcomes reported and fast recovery in treatment and control groups, there is little room for a treatment to improve results. | relative time to clinical response of wellbeing, 2.4% lower, relative time 0.98, p = 0.96, treatment 14, control 15. |
| [Sawanpanyalert], 9/9/2021, retrospective, Thailand, South Asia, peer-reviewed, 11 authors, dosage varies, this trial uses multiple treatments in the treatment arm (combined with lopinavir/ritonavir or darunavir/ritonavir) - results of individual treatments may vary. | risk of death, ICU, intubation, or high-flow oxygen, 42.0% lower, RR 0.58, p = 0.37, within 4 days of symptom onset, RR approximated with OR. |
| [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%), NNT 2.5, relative risk is not 0 because of continuity correction due to zero events (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%), NNT 1.7, relative risk is not 0 because of continuity correction due to zero events (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 death/hospitalization, 36.7% lower, RR 0.63, p = 0.58, treatment 5 of 231 (2.2%), control 8 of 234 (3.4%), NNT 80, COVID-19 adjudicated hospitalization/death. |
| risk of hospitalization, 49.4% lower, RR 0.51, p = 0.38, treatment 4 of 231 (1.7%), control 8 of 234 (3.4%), NNT 59, COVID-19 adjudicated hospitalization. | |
| risk of death/hospitalization, 49.4% lower, RR 0.51, p = 0.29, treatment 5 of 231 (2.2%), control 10 of 234 (4.3%), NNT 47, all hospitalization/death. | |
| risk of hospitalization, 59.5% lower, RR 0.41, p = 0.17, treatment 4 of 231 (1.7%), control 10 of 234 (4.3%), NNT 39, all hospitalizations. | |
| risk of no recovery at day 14, 20.0% lower, RR 0.80, p = 0.21, treatment 231, control 234. | |
| [Sobngwi], 7/29/2021, Randomized Controlled Trial, Cameroon, Africa, preprint, 16 authors, dosage 400mg days 1-5, this trial compares with another treatment - results may be better when compared to placebo. | risk of no recovery, 51.6% lower, RR 0.48, p = 0.44, treatment 2 of 95 (2.1%), control 4 of 92 (4.3%), NNT 45, day 10. |
| risk of no recovery, 3.2% lower, RR 0.97, p = 1.00, treatment 18 of 95 (18.9%), control 18 of 92 (19.6%), NNT 162, day 3. | |
| risk of no virological cure, 3.2% lower, RR 0.97, p = 0.88, treatment 32 of 95 (33.7%), control 32 of 92 (34.8%), NNT 91, day 10. | |
| [Su], 12/23/2020, retrospective, China, Asia, peer-reviewed, 9 authors, dosage 400mg days 1-10, 400mg daily for 10-14 days. | risk of 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 1,817 (0.4%), control 54 of 3,724 (1.5%), NNT 94, adjusted per study, odds ratio converted to relative risk. |
| risk of hospitalization, 38.6% lower, RR 0.61, p = 0.001, treatment 171 of 1,817 (9.4%), control 617 of 3,724 (16.6%), NNT 14, adjusted per study, odds ratio converted to relative risk. | |
| [Szente 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%), NNT 47, 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%), NNT 47, adjusted per study, odds ratio converted to relative risk, HCQ vs. anything else. | |
| [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 2,604 (9.1%), NNT 13, HCQ treatment started early vs. non-HCQ. |
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 pooled analysis, which may differ from the effect a paper
focuses on. Other outcomes are used in outcome specific analyses.
| [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%), NNT 5.1. | |
| [Abdulrahman], 11/30/2020, retrospective, propensity score matching, 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%), NNT 223, PSM. |
| risk of death/intubation, 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, multiple regions, peer-reviewed, baseline oxygen requirements 95.4%, 58 authors, excluded in exclusion analyses: very late stage, >50% on oxygen/ventilation at baseline. | 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%), NNT 192. |
| [Aghajani], 4/29/2021, retrospective, Iran, Middle East, peer-reviewed, 7 authors. | risk of death, 19.5% lower, RR 0.81, p = 0.09, treatment 553, control 438, multivariate Cox proportional regression. |
| [Alamdari], 9/9/2020, retrospective, Iran, Middle East, peer-reviewed, 14 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely. | risk of death, 55.0% lower, RR 0.45, p = 0.03, treatment 54 of 427 (12.6%), control 9 of 32 (28.1%), NNT 6.5. |
| [Albani], 8/30/2020, retrospective, Italy, Europe, peer-reviewed, 11 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically. | risk of death, 18.4% lower, RR 0.82, p = 0.15, 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 = 0.54, 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 = 0.70, 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%), NNT 5.8, odds ratio converted to relative risk. |
| [Alghamdi], 8/4/2021, retrospective, Saudi Arabia, Middle East, peer-reviewed, 1 author, excluded in exclusion analyses: unadjusted results with no group details, very late stage, ICU patients. | risk of death, 39.2% higher, RR 1.39, p = 0.52, treatment 29 of 128 (22.7%), control 7 of 43 (16.3%). |
| [Alghamdi (B)], 3/31/2021, retrospective, Saudi Arabia, Middle East, peer-reviewed, 10 authors, excluded in exclusion analyses: confounding by indication is likely and adjustments do not consider COVID-19 severity. | risk of death, 6.9% higher, RR 1.07, p = 0.88, treatment 44 of 568 (7.7%), control 15 of 207 (7.2%). |
| [Alhamlan], 7/16/2021, retrospective, database analysis, Saudi Arabia, Middle East, preprint, 10 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically. | risk of death, 52.0% higher, RR 1.52, p = 0.57. |
| [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%), NNT 17. |
| 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%), NNT 46. | |
| [Alotaibi], 9/14/2021, retrospective, Saudi Arabia, Middle East, peer-reviewed, 11 authors, this trial compares with another treatment - results may be better when compared to placebo. | risk of death, 133.5% higher, RR 2.33, p = 0.05, treatment 193, control 244, multivariate. |
| [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, excluded in exclusion analyses: confounding by indication is likely and adjustments do not consider COVID-19 severity. | risk of death, 4.3% lower, RR 0.96, p = 0.83, treatment 48 of 367 (13.1%), control 50 of 367 (13.6%), NNT 183, 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, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 63.0% lower, RR 0.37, p = 0.008, treatment 122 of 605 (20.2%), control 27 of 49 (55.1%), NNT 2.9. |
| [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 1,202 (13.5%), control 108 of 409 (26.4%), NNT 7.7. |
| [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, excluded in exclusion analyses: substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely. | 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 1,857 (12.8%), control 49 of 162 (30.2%), NNT 5.7, adjusted per study, odds ratio converted to relative risk. |
| [Babalola], 10/1/2021, Single Blind Randomized Controlled Trial, Nigeria, Africa, preprint, 6 authors, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary. | risk of no hospital discharge, 54.5% higher, RR 1.55, p = 0.20, treatment 17 of 30 (56.7%), control 11 of 30 (36.7%), day 7. |
| risk of no virological cure, 9.5% lower, RR 0.90, p = 0.78, treatment 19 of 30 (63.3%), control 21 of 30 (70.0%), NNT 15, day 5 mid-recovery. | |
| [Barbosa], 4/12/2020, retrospective, USA, North America, preprint, 5 authors, excluded in exclusion analyses: excessive unadjusted differences between groups. | risk of death, 147.0% higher, RR 2.47, p = 0.58, treatment 2 of 17 (11.8%), control 1 of 21 (4.8%). |
| [Barra], 7/31/2021, retrospective, Argentina, South America, preprint, 12 authors, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 10.8% lower, RR 0.89, p = 1.00, treatment 2 of 18 (11.1%), control 81 of 650 (12.5%), NNT 74, unadjusted. |
| [Barrat-Due], 7/13/2021, Double Blind Randomized Controlled Trial, Norway, Europe, peer-reviewed, 41 authors. | risk of death, 120.0% higher, RR 2.20, p = 0.35, treatment 4 of 45 (8.9%), control 2 of 48 (4.2%), adjusted per study. |
| [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%), NNT 6.6, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm). |
| [Berenguer], 8/3/2020, retrospective, Spain, Europe, peer-reviewed, 8 authors. | risk of death, 18.2% lower, RR 0.82, p < 0.001, treatment 681 of 2,618 (26.0%), control 438 of 1,377 (31.8%), NNT 17. |
| [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 1,498 (15.8%), control 28 of 147 (19.0%), NNT 30. |
| [Bielza], 12/11/2020, retrospective, Spain, Europe, peer-reviewed, median age 87.0, 24 authors, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 21.5% lower, RR 0.78, p = 0.09, treatment 33 of 91 (36.3%), control 249 of 539 (46.2%), NNT 10. |
| [Boari], 11/17/2020, retrospective, Italy, Europe, peer-reviewed, 20 authors, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 54.5% lower, RR 0.45, p < 0.001, treatment 41 of 202 (20.3%), control 25 of 56 (44.6%), NNT 4.1. |
| [Bosaeed], 4/30/2021, Randomized Controlled Trial, Saudi Arabia, Middle East, peer-reviewed, 30 authors, excluded in exclusion analyses: very late stage, >50% on oxygen/ventilation at baseline. | risk of death, 3.7% lower, RR 0.96, p = 0.91, treatment 14 of 125 (11.2%), control 15 of 129 (11.6%), NNT 234, 90 days. |
| risk of death, 28.6% lower, RR 0.71, p = 0.45, treatment 9 of 125 (7.2%), control 13 of 129 (10.1%), NNT 35, 28 days. | |
| risk of death, 65.1% higher, RR 1.65, p = 0.68, treatment 8 of 125 (6.4%), control 5 of 129 (3.9%), 14 days. | |
| risk of mechanical ventilation, 8.4% higher, RR 1.08, p = 0.78, treatment 21 of 125 (16.8%), control 20 of 129 (15.5%). | |
| risk of ICU admission, 31.0% higher, RR 1.31, p = 0.24, treatment 33 of 125 (26.4%), control 26 of 129 (20.2%). | |
| recovery time, 28.6% higher, relative time 1.29, p = 0.29, treatment 125, control 129. | |
| hospitalization time, 12.5% higher, relative time 1.12, p = 0.42, treatment 125, control 129. | |
| risk of no virological cure, 2.6% lower, RR 0.97, p = 0.75, treatment 100 of 125 (80.0%), control 106 of 129 (82.2%), NNT 46. | |
| [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%), NNT 10, adjusted per study, odds ratio converted to relative risk. |
| [Budhiraja], 11/18/2020, retrospective, India, South Asia, preprint, 12 authors, excluded in exclusion analyses: excessive unadjusted differences between groups. | risk of death, 65.4% lower, RR 0.35, p < 0.001, treatment 69 of 834 (8.3%), control 34 of 142 (23.9%), NNT 6.4. |
| [Burdick], 11/26/2020, prospective, USA, North America, peer-reviewed, 14 authors. | risk of death, 59.0% higher, RR 1.59, p = 0.12, treatment 142, control 148, adjusted per study, all patients. |
| risk of death, 71.0% lower, RR 0.29, p = 0.01, treatment 26, control 17, adjusted per study, subgroup of patients where treatment is predicted to be beneficial. | |
| [Byakika-Kibwika], 6/4/2021, Randomized Controlled Trial, Uganda, Africa, preprint, 17 authors. | recovery time, no change, relative time 1.00, p = 0.91, treatment 36, control 29. |
| relative improvement in Ct value, 29.3% better, RR 0.71, p = 0.47, treatment 15, control 15. | |
| risk of no virological cure, 2.6% higher, RR 1.03, p = 1.00, treatment 35 of 55 (63.6%), control 31 of 50 (62.0%), day 6. | |
| risk of no virological cure, 6.7% higher, RR 1.07, p = 0.85, treatment 27 of 55 (49.1%), control 23 of 50 (46.0%), day 10. | |
| [Calderón], 11/23/2021, retrospective, Mexico, North America, peer-reviewed, 7 authors, dosage 200mg bid days 1-7. | risk of death, 214.8% higher, RR 3.15, p = 0.38, treatment 5 of 27 (18.5%), control 1 of 17 (5.9%). |
| risk of mechanical ventilation, 651.9% higher, RR 7.52, p = 0.15, treatment 4 of 27 (14.8%), control 0 of 17 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm). | |
| risk of ICU admission, 145.5% higher, RR 2.45, p < 0.001, treatment 16 of 27 (59.3%), control 0 of 17 (0.0%), adjusted per study. | |
| hospitalization time, 107.4% higher, relative time 2.07, p = 0.006, treatment 27, control 17. | |
| [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%), NNT 2.4. |
| [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%), NNT 5.0. |
| [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 4,542 (17.7%), control 957 of 3,533 (27.1%), NNT 11. |
| [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%), NNT 211, 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, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 33.1% lower, RR 0.67, p = 0.17, treatment 8 of 29 (27.6%), control 195 of 473 (41.2%), NNT 7.3. |
| [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%), NNT 17, 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%), NNT 3.9. |
| [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%), NNT 7.5. |
| 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, excluded in exclusion analyses: excessive unadjusted differences between groups. | 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, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 45.6% lower, RR 0.54, p < 0.001, treatment 55 of 307 (17.9%), control 108 of 328 (32.9%), NNT 6.7. |
| [Cravedi], 7/10/2020, retrospective, USA, North America, peer-reviewed, mean age 60.0, 25 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely. | 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%), NNT 4.1, adjusted per study. |
| [Davido], 8/2/2020, retrospective, France, Europe, peer-reviewed, 14 authors. | risk of intubation/hospitalization, 55.0% lower, RR 0.45, p = 0.04, treatment 12 of 80 (15.0%), control 13 of 40 (32.5%), NNT 5.7. |
| [De Luna], 12/14/2020, retrospective, Dominican Republic, Caribbean, preprint, 10 authors, excluded in exclusion analyses: unadjusted results with no group details, substantial unadjusted confounding by indication likely. | risk of death, 104.5% higher, RR 2.05, p = 0.69, treatment 15 of 132 (11.4%), control 1 of 18 (5.6%). |
| [De Rosa], 5/1/2021, retrospective, Italy, Europe, peer-reviewed, 20 authors. | risk of death, 35.0% lower, RR 0.65, p = 0.02, treatment 118 of 731 (16.1%), control 80 of 280 (28.6%), NNT 8.0, adjusted per study, odds ratio converted to relative risk, multivariate logistic regression, patients alive at day 7. |
| [Di Castelnuovo], 1/29/2021, retrospective, Italy, Europe, peer-reviewed, 112 authors. | risk of death, 40.0% lower, RR 0.60, p < 0.001, treatment 3,270, control 1,000, odds ratio converted to relative risk, multivariate Cox proportional hazards model 4, control prevalence approximated with overall prevalence. |
| [Di Castelnuovo (B)], 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 2,634 (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%), NNT 24. |
| 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%), NNT 40. | |
| [Dubernet], 8/20/2020, retrospective, France, Europe, 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%), NNT 2.4. |
| [Falcone], 11/19/2020, prospective, propensity score matching, Italy, Europe, peer-reviewed, 19 authors. | risk of death, 65.0% lower, RR 0.35, p = 0.20, treatment 40 of 238 (16.8%), control 30 of 77 (39.0%), NNT 4.5, 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%), NNT 4.5, 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%), NNT 4.5, 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. | |
| [Ferreira], 11/26/2021, retrospective, Brazil, South America, peer-reviewed, 5 authors, 12 March, 2020 - 8 July, 2020, dosage not specified. | risk of death, 151.5% higher, RR 2.51, p = 0.03, treatment 17 of 111 (15.3%), control 11 of 81 (13.6%), odds ratio converted to relative risk, multivariate. |
| risk of death/intubation, 45.9% higher, RR 1.46, p = 0.23, treatment 30 of 111 (27.0%), control 15 of 81 (18.5%). | |
| risk of death/intubation/ICU, 61.3% higher, RR 1.61, p = 0.04, treatment 42 of 111 (37.8%), control 19 of 81 (23.5%). | |
| [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%), NNT 3.0. |
| [Fried], 8/28/2020, retrospective, database analysis, USA, North America, peer-reviewed, 11 authors, excluded in exclusion analyses: excessive unadjusted differences between groups, substantial unadjusted confounding by indication likely. | risk of death, 27.0% higher, RR 1.27, p < 0.001, treatment 1,048 of 4,232 (24.8%), control 1,466 of 7,489 (19.6%). |
| [Frontera], 10/26/2020, retrospective, propensity score matching, USA, North America, preprint, median age 64.0, 14 authors, this trial uses multiple treatments in the treatment arm (combined with zinc) - results of individual treatments may vary. | risk of death, 37.0% lower, RR 0.63, p = 0.01, treatment 121 of 1,006 (12.0%), control 424 of 2,467 (17.2%), NNT 19, adjusted per study, PSM. |
| risk of death, 24.0% lower, RR 0.76, p = 0.02, treatment 121 of 1,006 (12.0%), control 424 of 2,467 (17.2%), NNT 19, adjusted per study, regression. | |
| [Gadhiya], 4/8/2021, retrospective, USA, North America, peer-reviewed, 4 authors, excluded in exclusion analyses: substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely. | risk of death, 4.8% higher, RR 1.05, p = 0.89, treatment 22 of 55 (40.0%), control 33 of 216 (15.3%), adjusted per study, odds ratio converted to relative risk, multivariate logistic regression. |
| [Geleris], 5/7/2020, retrospective, USA, North America, peer-reviewed, 12 authors, excluded in exclusion analyses: significant issues found with adjustments. | risk of death/intubation, 4.0% higher, RR 1.04, p = 0.76, treatment 262 of 811 (32.3%), control 84 of 565 (14.9%), adjusted per study. |
| [Gerlovin], 6/24/2021, retrospective, USA, North America, peer-reviewed, 21 authors. | risk of death, 22.0% higher, RR 1.22, p = 0.18, treatment 90 of 429 (21.0%), control 141 of 770 (18.3%), adjusted per study, HCQ+AZ. |
| risk of death, 21.0% higher, RR 1.21, p = 0.33, treatment 49 of 228 (21.5%), control 141 of 770 (18.3%), adjusted per study, HCQ. | |
| risk of mechanical ventilation, 55.0% higher, RR 1.55, p = 0.02, treatment 64 of 429 (14.9%), control 69 of 770 (9.0%), adjusted per study, HCQ+AZ. | |
| risk of mechanical ventilation, 33.0% higher, RR 1.33, p = 0.25, treatment 32 of 228 (14.0%), control 69 of 770 (9.0%), adjusted per study, HCQ. | |
| [Goldman], 5/27/2020, retrospective, multiple countries, multiple regions, peer-reviewed, 26 authors, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 22.3% lower, RR 0.78, p = 0.46, treatment 10 of 109 (9.2%), control 34 of 288 (11.8%), NNT 38. |
| [Gonzalez], 2/23/2021, Double Blind Randomized Controlled Trial, Mexico, North America, preprint, 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%), NNT 9.8. |
| 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%), NNT 16. | |
| risk of no hospital discharge, 12.1% higher, RR 1.12, p = 1.00, treatment 3 of 33 (9.1%), control 3 of 37 (8.1%). | |
| [Gonzalez (B)], 8/21/2020, retrospective, database analysis, Spain, Europe, preprint, 25 authors. | risk of death, 26.6% lower, RR 0.73, p = 0.06, treatment 1,246 of 8,476 (14.7%), control 341 of 1,168 (29.2%), NNT 6.9, adjusted per study, odds ratio converted to relative risk. |
| [Guglielmetti], 10/25/2021, retrospective, Italy, Europe, peer-reviewed, 19 authors, 21 February, 2020 - 15 May, 2020. | risk of death, 28.0% lower, RR 0.72, p = 0.10, treatment 474, control 126, multivariable Cox proportional hazards. |
| [Guglielmetti (B)], 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%), NNT 17, 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, excluded in exclusion analyses: very late stage, >50% on oxygen/ventilation at baseline. | risk of death, 6.0% higher, RR 1.06, p = 0.41, treatment 631 of 1,761 (35.8%), control 153 of 454 (33.7%). |
| [Güner], 12/29/2020, retrospective, Turkey, Europe, peer-reviewed, 23 authors. | risk of ICU admission, 77.3% lower, RR 0.23, p = 0.16, treatment 604, control 100, IPTW multivariate analysis, HCQ vs. favipiravir. |
| [Heberto], 9/12/2020, prospective, Mexico, North America, peer-reviewed, 8 authors, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary. | risk of death, 53.9% lower, RR 0.46, p = 0.04, treatment 139, control 115, odds ratio converted to relative risk. |
| risk of mechanical ventilation, 65.1% lower, RR 0.35, p = 0.008, treatment 139, control 115, 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, excluded in exclusion analyses: very late stage, ICU patients. | risk of death, 64.7% lower, RR 0.35, p = 0.21, treatment 2 of 17 (11.8%), control 5 of 15 (33.3%), NNT 4.6, 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 (D)], 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 1,914 (22.6%), control 115 of 598 (19.2%), adjusted per study. |
| [Izoulet], 4/21/2020, retrospective, multiple countries, multiple regions, preprint, 1 author, dosage not specified, excluded in exclusion analyses: excessive unadjusted differences between groups. | risk of death, 85.0% lower, RR 0.15, p < 0.001. |
| [Jacobs], 7/6/2021, prospective, USA, North America, peer-reviewed, 14 authors, excluded in exclusion analyses: unadjusted results with no group details, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically. | risk of death, 6.6% lower, RR 0.93, p = 0.74, treatment 24 of 46 (52.2%), control 86 of 154 (55.8%), NNT 27. |
| [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%), NNT 69, 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-, 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%), NNT 9.2, 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%), NNT 66, 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, excluded in exclusion analyses: excessive unadjusted differences between groups. | risk of progression, 5.0% lower, RR 0.95, p = 1.00, treatment 11 of 349 (3.2%), control 5 of 151 (3.3%), NNT 627. |
| risk of progression, 54.8% lower, RR 0.45, p = 0.30, treatment 4 of 31 (12.9%), control 2 of 7 (28.6%), NNT 6.4, 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, excluded in exclusion analyses: substantial unadjusted confounding by indication likely. | 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. | |
| [Kokturk], 4/28/2021, retrospective, database analysis, Turkey, Europe, peer-reviewed, 68 authors. | risk of death, 3.8% higher, RR 1.04, p = 0.97, treatment 62 of 1,382 (4.5%), control 5 of 118 (4.2%), adjusted per study, odds ratio converted to relative risk. |
| [Komissarov], 6/30/2020, retrospective, Russia, Europe, preprint, 8 authors. | risk of viral load, 25.0% higher, RR 1.25, p = 0.45, treatment 26, control 10. |
| [Krishnan], 7/20/2020, retrospective, USA, North America, peer-reviewed, 13 authors, dosage not specified, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 20.4% lower, RR 0.80, p = 0.48, treatment 86 of 144 (59.7%), control 6 of 8 (75.0%), NNT 6.5. |
| [Kuderer], 5/28/2020, retrospective, USA, North America, peer-reviewed, 73 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely. | 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. |
| [Lagier], 6/4/2021, retrospective, France, Europe, preprint, 32 authors. | risk of death, 32.0% lower, RR 0.68, p = 0.004, treatment 93 of 1,270 (7.3%), control 146 of 841 (17.4%), NNT 10.0, adjusted per study, weighted multivariate Cox proportional hazards model. |
| [Lagier (B)], 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 3,119 (1.1%), control 58 of 618 (9.4%), NNT 12, adjusted per study. |
| [Lamback], 2/19/2021, retrospective, Brazil, South America, peer-reviewed, 10 authors, excluded in exclusion analyses: substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically. | risk of death, 8.9% lower, RR 0.91, p = 0.83, treatment 11 of 101 (10.9%), control 11 of 92 (12.0%), NNT 94. |
| 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%). | |
| [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%), NNT 4.9, adjusted per study. |
| [Lammers], 9/29/2020, prospective, Netherlands, Europe, peer-reviewed, 18 authors. | risk of death/ICU, 32.0% lower, RR 0.68, p = 0.02, treatment 30 of 189 (15.9%), control 101 of 498 (20.3%), NNT 23, 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 death/ICU, 38.9% lower, RR 0.61, p = 0.23, treatment 17 of 56 (30.4%), control 28 of 66 (42.4%), NNT 8.3, adjusted per study, odds ratio converted to relative risk. | |
| risk of death/ICU, 68.7% lower, RR 0.31, p = 0.11, treatment 4 of 36 (11.1%), control 11 of 31 (35.5%), NNT 4.1, 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%), NNT 4.7, adjusted per study. |
| [Lecronier], 7/11/2020, retrospective, France, Europe, peer-reviewed, baseline oxygen requirements 100.0%, 25 authors, HCQ vs. control, excluded in exclusion analyses: very late stage, >50% on oxygen/ventilation at baseline. | risk of death, 42.0% lower, RR 0.58, p = 0.24, treatment 9 of 38 (23.7%), control 9 of 22 (40.9%), NNT 5.8. |
| 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%), NNT 70. | |
| 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%), NNT 7.9. | |
| [Li], 1/18/2021, retrospective, China, Asia, peer-reviewed, 21 authors. | risk of no hospital discharge, 50.0% lower, RR 0.50, p = 0.09, 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 7,192, control 1,361, odds ratio converted to relative risk, univariate, control prevalence approximated with overall prevalence. |
| [Lotfy], 1/1/2021, retrospective, Saudi Arabia, Middle East, peer-reviewed, mean age 55.0, 3 authors, excluded in exclusion analyses: substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely. | 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, excluded in exclusion analyses: substantial unadjusted confounding by indication likely. | 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. |
| [Luo (B)], 5/21/2020, retrospective, China, Asia, peer-reviewed, 9 authors. | risk of death, 32.4% lower, RR 0.68, p = 0.72, treatment 19, control 264, multivariate, RR approximated with OR. |
| [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%), NNT 702. |
| 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 progression, 64.3% lower, RR 0.36, p = 0.02, treatment 5 of 36 (13.9%), control 14 of 36 (38.9%), NNT 4.0. |
| [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, excluded in exclusion analyses: treatment or control group size extremely small. | risk of death, 90.9% lower, RR 0.09, p = 0.17, treatment 1 of 11 (9.1%), control 1 of 1 (100.0%), NNT 1.1. |
| [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, excluded in exclusion analyses: unadjusted results with no group details, treatment or control group size extremely small. | risk of death, 59.3% lower, RR 0.41, p = 0.41, treatment 37 of 91 (40.7%), control 1 of 1 (100.0%), NNT 1.7. |
| [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%), NNT 6.4. |
| [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%), NNT 2.2, adjusted per study, odds ratio converted to relative risk. |
| [McGrail], 7/19/2020, retrospective, USA, North America, preprint, 2 authors, excluded in exclusion analyses: excessive unadjusted differences between groups. | 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%), NNT 3.7. |
| [Menardi], 9/30/2021, retrospective, Italy, Europe, peer-reviewed, 10 authors, excluded in exclusion analyses: excessive unadjusted differences between groups, substantial unadjusted confounding by indication likely. | risk of death, 35.2% lower, RR 0.65, p = 0.12, treatment 32 of 200 (16.0%), control 19 of 77 (24.7%), NNT 12. |
| [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 2,077 (27.7%), control 231 of 743 (31.1%), NNT 29, 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). |
| [Mohandas], 4/26/2021, retrospective, India, South Asia, peer-reviewed, 6 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, unadjusted results with no group details, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically. | risk of death, 81.0% higher, RR 1.81, p = 0.007, treatment 27 of 384 (7.0%), control 115 of 2,961 (3.9%). |
| [Mulhem], 4/7/2021, retrospective, database analysis, USA, North America, peer-reviewed, 3 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically. | risk of death, 28.3% higher, RR 1.28, p = 0.10, treatment 435 of 2,496 (17.4%), control 81 of 723 (11.2%), adjusted per study, odds ratio converted to relative risk, logistic regression. |
| [Nachega], 10/2/2020, retrospective, database analysis, DR 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%), NNT 5.5, 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 1,137, multivariate Cox. |
| [Núñez-Gil], 11/9/2020, retrospective, database analysis, multiple countries, multiple regions, 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%), NNT 12, 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%), NNT 47. |
| [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, RR approximated with OR. | |
| [Ozturk], 12/4/2020, retrospective, Turkey, Europe, peer-reviewed, 70 authors. | risk of death, 43.9% lower, RR 0.56, p = 0.14, treatment 165 of 1,127 (14.6%), control 6 of 23 (26.1%), NNT 8.7, 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%), NNT 79, adjusted per study. |
| [Pasquini], 8/23/2020, retrospective, Italy, Europe, peer-reviewed, 9 authors, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 16.4% lower, RR 0.84, p = 0.34, treatment 23 of 33 (69.7%), control 15 of 18 (83.3%), NNT 7.3. |
| [Peng], 12/4/2020, retrospective, China, Asia, peer-reviewed, 21 authors. | risk of progression, 10.8% lower, RR 0.89, p = 0.63, treatment 29 of 453 (6.4%), control 256 of 3,567 (7.2%), NNT 129, CQ/HCQ risk of AKI. |
| [Peters], 8/15/2020, retrospective, Netherlands, Europe, peer-reviewed, 21 authors, excluded in exclusion analyses: excessive unadjusted differences between groups. | risk of death, 9.0% higher, RR 1.09, p = 0.57, treatment 419 of 1,596 (26.3%), control 53 of 353 (15.0%), adjusted per study. |
| [Pinato], 8/18/2020, retrospective, multiple countries, multiple regions, 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%), NNT 4.1. |
| [Psevdos], 12/31/2020, retrospective, USA, North America, peer-reviewed, 3 authors, excluded in exclusion analyses: unadjusted results with no group details, no treatment details, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely. | 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, South 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%), NNT 1.6, day 7. |
| [Qin], 11/23/2020, retrospective, China, Asia, peer-reviewed, 17 authors, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 34.3% lower, RR 0.66, p = 0.61, treatment 3 of 43 (7.0%), control 75 of 706 (10.6%), NNT 27. |
| [Ramírez-García], 5/31/2021, retrospective, Spain, Europe, peer-reviewed, 5 authors, excluded in exclusion analyses: excessive unadjusted differences between groups, substantial unadjusted confounding by indication likely. | risk of death, 67.0% lower, RR 0.33, p < 0.001, treatment 48 of 350 (13.7%), control 22 of 53 (41.5%), NNT 3.6. |
| risk of ICU admission, 6.0% higher, RR 1.06, p = 1.00, treatment 35 of 350 (10.0%), control 5 of 53 (9.4%). | |
| [RECOVERY], 6/5/2020, Randomized Controlled Trial, United Kingdom, Europe, preprint, 29 authors, excluded in exclusion analyses: excessive dosage in late stage patients, results do not apply to typical dosages. | risk of death, 9.0% higher, RR 1.09, p = 0.15, treatment 421 of 1,561 (27.0%), control 790 of 3,155 (25.0%). |
| [Reis], 4/22/2021, Double Blind Randomized Controlled Trial, Brazil, South America, peer-reviewed, 18 authors, dosage 800mg day 1, 400mg days 2-10. | risk of death, 66.0% lower, RR 0.34, p = 1.00, treatment 0 of 214 (0.0%), control 1 of 227 (0.4%), NNT 227, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm). |
| risk of hospitalization, 24.0% lower, RR 0.76, p = 0.57, treatment 8 of 214 (3.7%), control 11 of 227 (4.8%), NNT 90, ITT, Cox proportional hazards. | |
| risk of no virological cure, 4.1% lower, RR 0.96, p = 0.10, treatment 97 of 185 (52.4%), control 102 of 179 (57.0%), NNT 22, adjusted per study, odds ratio converted to relative risk, ITT, mixed-effect logistic model. | |
| [Rivera], 7/22/2020, retrospective, USA, North America, peer-reviewed, 45 authors. | risk of death, 2.4% higher, RR 1.02, p = 0.92, 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, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 59.0% lower, RR 0.41, p = 0.23, treatment 8 of 39 (20.5%), control 2 of 4 (50.0%), NNT 3.4. |
| [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 1,148 (21.9%), control 17 of 60 (28.3%), NNT 15. |
| [Rodriguez-Nava], 11/5/2020, retrospective, USA, North America, peer-reviewed, median age 68.0, 8 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, excessive unadjusted differences between groups, unadjusted results with no group details. | 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. |
| [Rogado], 5/29/2020, retrospective, Spain, Europe, peer-reviewed, 9 authors. | risk of death, 91.6% lower, RR 0.08, p = 0.02, treatment 1 of 8 (12.5%), control 7 of 9 (77.8%), NNT 1.5, odds ratio converted to relative risk, multivariate logistic regression. |
| [Roger], 7/10/2021, prospective, France, Europe, peer-reviewed, 34 authors, excluded in exclusion analyses: substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically. | risk of death, no change, RR 1.00, p = 0.94, treatment 53 of 289 (18.3%), control 120 of 677 (17.7%), odds ratio converted to relative risk. |
| [Roig], 1/31/2021, retrospective, Spain, Europe, peer-reviewed, 6 authors, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 15.6% lower, RR 0.84, p = 0.76, treatment 33 of 67 (49.3%), control 7 of 12 (58.3%), NNT 11. |
| [Roomi], 8/13/2020, retrospective, USA, North America, peer-reviewed, 11 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely. | risk of death, 37.7% higher, RR 1.38, p = 0.54, treatment 13 of 144 (9.0%), control 6 of 32 (18.8%), NNT 10, 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. |
| [Réa-Neto], 4/27/2021, Randomized Controlled Trial, Brazil, South America, peer-reviewed, 6 authors. | risk of death, 57.0% higher, RR 1.57, p = 0.20, treatment 16 of 53 (30.2%), control 10 of 52 (19.2%). |
| risk of mechanical ventilation, 115.0% higher, RR 2.15, p = 0.03, treatment 53, control 52. | |
| 9-point scale clinical status, 147.0% higher, RR 2.47, p = 0.02, treatment 53, control 52, RR approximated with OR. | |
| [Saib], 6/9/2021, prospective, propensity score matching, France, Europe, peer-reviewed, 9 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely. | risk of death/intubation, 125.0% higher, RR 2.25, p = 0.23, treatment 9 of 52 (17.3%), control 4 of 52 (7.7%), PSM. |
| [Salazar], 11/4/2020, retrospective, USA, North America, peer-reviewed, 19 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, unadjusted results with no group details. | 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, excluded in exclusion analyses: substantial unadjusted confounding by indication likely. | 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 = 0.10, treatment 28 of 121 (23.1%), control 58 of 124 (46.8%), NNT 4.2, 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 death/intubation, 16.7% lower, RR 0.83, p = 0.21, treatment 51 of 121 (42.1%), control 63 of 124 (50.8%), NNT 12, odds ratio converted to relative risk, univariate. | |
| [Sammartino], 5/10/2021, retrospective, propensity score matching, USA, North America, peer-reviewed, 7 authors, excluded in exclusion analyses: substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically. | risk of death, 240.0% higher, RR 3.40, p = 0.002, treatment 137, control 191, PSM, model 1a, RR approximated with OR. |
| [Sands], 1/1/2021, retrospective, database analysis, USA, North America, peer-reviewed, 10 authors, excluded in exclusion analyses: includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons, substantial unadjusted confounding by indication likely. | 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, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, significant unadjusted confounding possible, unadjusted results with no group details. | risk of death, 45.0% higher, RR 1.45, p = 0.07, treatment 40 of 94 (42.6%), control 27 of 92 (29.3%). |
| [Sarhan], 11/2/2021, Randomized Controlled Trial, Egypt, Africa, peer-reviewed, 8 authors, 1 October, 2020 - 10 March, 2021, this trial compares with another treatment - results may be better when compared to placebo, excluded in exclusion analyses: very late stage, >50% on oxygen/ventilation at baseline, significant unadjusted differences between groups. | risk of death, 25.7% lower, RR 0.74, p = 0.39, treatment 12 of 56 (21.4%), control 15 of 52 (28.8%), NNT 13. |
| risk of no hospital discharge, 25.7% lower, RR 0.74, p = 0.39, treatment 12 of 56 (21.4%), control 15 of 52 (28.8%), NNT 13. | |
| hospitalization time, 25.0% higher, relative time 1.25, p = 0.06, treatment 56, control 52. | |
| [Sbidian], 6/19/2020, retrospective, database analysis, France, Europe, preprint, 21 authors, excluded in exclusion analyses: significant issues found with adjustments. | risk of death, 5.0% higher, RR 1.05, p = 0.74, treatment 111 of 623 (17.8%), control 830 of 3,792 (21.9%), NNT 25, adjusted per study, whole population HCQ AIPTW adjusted. |
| risk of no hospital discharge, 20.0% lower, RR 0.80, p = 0.002, treatment 623, control 3,792, adjusted per study, whole population HCQ AIPTW adjusted. | |
| [Schwartz], 6/18/2021, Double Blind Randomized Controlled Trial, Canada, North America, peer-reviewed, 20 authors, dosage 800mg day 1, 400mg days 2-5. | risk of ICU admission, 133.3% higher, RR 2.33, p = 1.00, treatment 1 of 111 (0.9%), control 0 of 37 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm). |
| risk of hospitalization, 533.3% higher, RR 6.33, p = 0.57, treatment 4 of 111 (3.6%), control 0 of 37 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm). | |
| risk of ICU admission, 141.9% higher, RR 2.42, p = 1.00, treatment 1 of 74 (1.4%), control 0 of 31 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm), per-protocol. | |
| risk of hospitalization, 141.9% higher, RR 2.42, p = 1.00, treatment 1 of 74 (1.4%), control 0 of 31 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm), per-protocol. | |
| [Self], 11/9/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 33 authors. | risk of death, 6.2% higher, RR 1.06, p = 0.85, treatment 25 of 241 (10.4%), control 25 of 236 (10.6%), NNT 455, 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%), NNT 3.1. |
| [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%), NNT 22. |
| [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, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 15.4% lower, RR 0.85, p < 0.001, treatment 686 of 5,047 (13.6%), control 3,923 of 24,404 (16.1%), NNT 40. |
| [Signes-Costa], 12/16/2020, retrospective, multiple countries, multiple regions, peer-reviewed, 28 authors. | risk of death, 47.0% lower, RR 0.53, p < 0.001, treatment 4,854, control 993, adjusted per study. |
| [Singh (B)], 6/8/2021, Randomized Controlled Trial, India, South Asia, preprint, 13 authors, this trial uses multiple treatments in the treatment arm (combined with ribavirin) - results of individual treatments may vary. | risk of death, 47.5% lower, RR 0.53, p = 0.45, treatment 3 of 20 (15.0%), control 6 of 21 (28.6%), NNT 7.4, severe. |
| risk of death, 50.0% lower, RR 0.50, p = 0.48, treatment 3 of 37 (8.1%), control 6 of 37 (16.2%), NNT 12, all patients. | |
| risk of no recovery, 14.1% lower, RR 0.86, p = 0.76, treatment 9 of 20 (45.0%), control 11 of 21 (52.4%), NNT 14, severe. | |
| risk of no recovery, 8.3% lower, RR 0.92, p = 1.00, treatment 11 of 37 (29.7%), control 12 of 37 (32.4%), NNT 37, all patients. | |
| [Singh], 5/19/2020, retrospective, database analysis, USA, North America, preprint, 4 authors, excluded in exclusion analyses: confounding by indication is likely and adjustments do not consider COVID-19 severity. | risk of death, 5.0% lower, RR 0.95, p = 0.72, treatment 104 of 910 (11.4%), control 109 of 910 (12.0%), NNT 182. |
| 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%), NNT 83. | |
| [Sivapalan], 6/3/2021, Double Blind Randomized Controlled Trial, Denmark, Europe, peer-reviewed, 32 authors. | risk of death, 92.0% lower, RR 0.08, p = 0.32, treatment 1 of 61 (1.6%), control 2 of 56 (3.6%), NNT 52, adjusted per study. |
| risk of ICU admission, 22.4% higher, RR 1.22, p = 1.00, treatment 4 of 61 (6.6%), control 3 of 56 (5.4%). | |
| relative days alive and discharged from hospital within 14 days (inverse), 8.4% worse, RR 1.08, p = 0.36, treatment 61, control 56, adjusted per study. | |
| [Smith], 5/31/2021, retrospective, USA, North America, preprint, 4 authors, excluded in exclusion analyses: immortal time bias may significantly affect results. | risk of death, 27.2% lower, RR 0.73, p = 0.002, treatment 19 of 37 (51.4%), control 182 of 218 (83.5%), NNT 3.1, odds ratio converted to relative risk, >3g HCQ and >1g AZ, multivariable cox proportional hazard regression. |
| [Solh], 10/20/2020, retrospective, database analysis, USA, North America, preprint, 5 authors, excluded in exclusion analyses: very late stage, >50% on oxygen/ventilation at baseline, substantial unadjusted confounding by indication likely. | 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, excluded in exclusion analyses: excessive dosage in late stage patients, results do not apply to typical dosages, very late stage, >50% on oxygen/ventilation at baseline. | 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, excluded in exclusion analyses: very late stage, >50% on oxygen/ventilation at baseline, substantial unadjusted confounding by indication likely. | 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, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons. | risk of death, 18.1% lower, RR 0.82, p < 0.001, treatment 346 of 692 (50.0%), control 1,606 of 2,630 (61.1%), NNT 9.0, 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 2,630 (15.2%), adjusted per study, day 30. | |
| [Stewart], 3/17/2021, retrospective, USA, North America, peer-reviewed, 37 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons. | 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. |
| [Stewart (B)], 3/17/2021, retrospective, USA, North America, peer-reviewed, 37 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons. | risk of mechanical ventilation, 29.0% higher, RR 1.29, p = 0.09, treatment 48 of 305 (15.7%), control 95 of 1,302 (7.3%), adjusted per study, Aetion, HCQ. |
| [Stewart (C)], 3/17/2021, retrospective, USA, North America, peer-reviewed, 37 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons. | risk of death, 16.0% higher, RR 1.16, p = 0.26, treatment 428 of 1,711 (25.0%), control 123 of 688 (17.9%), adjusted per study, COTA/HMH, HCQ+AZ. |
| [Stewart (D)], 3/17/2021, retrospective, USA, North America, peer-reviewed, 37 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons. | risk of death, 90.0% higher, RR 1.90, p = 0.09, treatment 46 of 208 (22.1%), control 47 of 1,334 (3.5%), adjusted per study, Dascena, HCQ+AZ. |
| [Stewart (E)], 3/17/2021, retrospective, USA, North America, peer-reviewed, 37 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons. | risk of death, 9.0% higher, RR 1.09, p = 0.65, treatment 212 of 1,157 (18.3%), control 203 of 1,101 (18.4%), NNT 873, adjusted per study, Health Catalyst, HCQ+AZ. |
| [Stewart (F)], 3/17/2021, retrospective, USA, North America, peer-reviewed, 37 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons. | 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. |
| [Stewart (G)], 3/17/2021, retrospective, USA, North America, peer-reviewed, 37 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons. | risk of death, 1.0% lower, RR 0.99, p = 0.95, treatment 66 of 578 (11.4%), control 188 of 1,243 (15.1%), NNT 27, adjusted per study, TriNetX, HCQ+AZ. |
| [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%), NNT 15. |
| [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 = 0.02, treatment 449 of 1,308 (34.3%), control 183 of 439 (41.7%), NNT 14, odds ratio converted to relative risk. |
| [Taieb], 6/30/2021, retrospective, Senegal, Africa, peer-reviewed, 29 authors. | risk of no hospital discharge, 38.7% lower, RR 0.61, p = 0.02, treatment 674, control 252, multivariate, RR approximated with OR. |
| [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%), NNT 25. |
| [Tehrani], 10/30/2020, retrospective, Sweden, Europe, peer-reviewed, 5 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, unadjusted results with no group details. | risk of death, 13.4% lower, RR 0.87, p = 0.63, treatment 16 of 65 (24.6%), control 54 of 190 (28.4%), NNT 26. |
| [Texeira], 12/31/2020, retrospective, USA, North America, peer-reviewed, 6 authors, excluded in exclusion analyses: unadjusted results with no group details, no treatment details, substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely. | risk of death, 79.3% higher, RR 1.79, p = 0.10, treatment 17 of 65 (26.2%), control 14 of 96 (14.6%). |
| [Thompson], 2/9/2021, Double Blind Randomized Controlled Trial, USA, North America, preprint, 1 author. | risk of death, 6.2% higher, RR 1.06, p = 0.85, treatment 25 of 241 (10.4%), control 25 of 236 (10.6%), NNT 455, adjusted per study, odds ratio converted to relative risk, day 28. |
| risk of death, 51.0% higher, RR 1.51, p = 0.28, treatment 18 of 241 (7.5%), control 14 of 236 (5.9%), adjusted per study, odds ratio converted to relative risk, day 14. | |
| risk of 7-point scale, 3.1% higher, RR 1.03, p = 0.87, treatment 241, control 236, day 28, RR approximated with OR. | |
| risk of 7-point scale, 2.0% lower, RR 0.98, p = 0.91, treatment 241, control 236, day 14, RR approximated with OR. | |
| [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%), NNT 6.0. |
| [Turrini], 6/11/2021, retrospective, Italy, Europe, peer-reviewed, 16 authors. | risk of death, 9.8% lower, RR 0.90, p = 0.15, treatment 103 of 160 (64.4%), control 33 of 45 (73.3%), NNT 11, adjusted per study, odds ratio converted to relative risk, multivariate. |
| [Ubaldo], 2/1/2021, retrospective, Philippines, Asia, peer-reviewed, 3 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, very late stage, ICU patients, unadjusted results with no group details. | risk of death, 18.4% lower, RR 0.82, p = 0.64, treatment 17 of 25 (68.0%), control 5 of 6 (83.3%), NNT 6.5, 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, excluded in exclusion analyses: very late stage, >50% on oxygen/ventilation at baseline. | risk of death, 6.0% higher, RR 1.06, p = 1.00, treatment 7 of 67 (10.4%), control 6 of 61 (9.8%). |
| [Uygen], 9/15/2021, retrospective, Turkey, Europe, peer-reviewed, 4 authors. | time to viral-, 12.2% lower, relative time 0.88, p = 0.05, treatment 15, control 25. |
| [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%), NNT 10. |
| [Vernaz], 12/31/2020, retrospective, propensity score matching, Switzerland, Europe, peer-reviewed, 15 authors, excluded in exclusion analyses: substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely. | risk of death, 15.3% lower, RR 0.85, p = 0.71, treatment 12 of 93 (12.9%), control 16 of 105 (15.2%), NNT 43, HCQ vs. SOC, PSM. |
| hospitalization time, 49.0% higher, relative time 1.49, p = 0.002, treatment 93, control 105, HCQ vs. SOC, PSM. | |
| [Wang], 6/10/2020, retrospective, database analysis, USA, North America, preprint, 3 authors, excluded in exclusion analyses: confounding by indication is likely and adjustments do not consider COVID-19 severity. | risk of death, 5.8% lower, RR 0.94, p = 0.63, treatment 1,866, control 5,726, odds ratio converted to relative risk. |
| [Xia], 2/11/2020, retrospective, China, Asia, preprint, 1 author, excluded in exclusion analyses: minimal details provided. | 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%), NNT 3.3. |
| [Yegerov], 1/8/2021, retrospective, Kazakhstan, Asia, preprint, 8 authors, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 95.3% lower, RR 0.05, p = 1.00, treatment 0 of 23 (0.0%), control 20 of 1,049 (1.9%), NNT 52, relative risk is not 0 because of continuity correction due to zero events (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 1,291 (2.5%), NNT 49, 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 2,604 (9.1%), NNT 13, 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%), NNT 3.5. |
| [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%), NNT 6.1, 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%), NNT 4.3, adjusted per study. |
| [Çivriz Bozdağ], 9/15/2021, retrospective, Turkey, Europe, peer-reviewed, 62 authors, excluded in exclusion analyses: substantial time varying confounding likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically. | risk of death, 399.2% higher, RR 4.99, p = 0.003, treatment 35, control 140. |
| [Çiyiltepe], 4/30/2021, retrospective, Turkey, Europe, peer-reviewed, 5 authors, excluded in exclusion analyses: treatment group only includes patients where treatment failed resulting in ICU admission. | risk of death, 3.2% lower, RR 0.97, p = 0.85, treatment 69 of 95 (72.6%), control 39 of 52 (75.0%), NNT 42. |
| [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%), NNT 4.7, 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%), NNT 4.1, 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%), NNT 4.4, HCQ+AZ or CQ. |
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 pooled analysis, which may differ from the effect a paper
focuses on. Other outcomes are used in outcome specific analyses.
| [Abella], 9/30/2020, Randomized Controlled Trial, USA, North America, peer-reviewed, 18 authors. | risk of case, 5.0% lower, RR 0.95, p = 1.00, treatment 4 of 64 (6.2%), control 4 of 61 (6.6%), NNT 325. |
| [Agarwal], 9/14/2021, prospective, India, South Asia, preprint, 1 author. | risk of hospitalization, 94.8% lower, RR 0.05, p = 0.61, treatment 0 of 29 (0.0%), control 17 of 455 (3.7%), NNT 27, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm). |
| relative severity, 26.9% better, RR 0.73, p = 0.21, treatment 29, control 455. | |
| risk of case, 4.6% higher, RR 1.05, p = 0.81, treatment 6 of 29 (20.7%), control 90 of 455 (19.8%). | |
| [Ahmed], 11/23/2021, retrospective, Saudi Arabia, Middle East, peer-reviewed, 7 authors. | risk of case, 99.3% lower, RR 0.007, p = 0.08, treatment 0 of 50 (0.0%) cases, 13 of 50 (26.0%) controls, NNT 1.7, case control OR. |
| [Alegiani], 4/15/2021, retrospective, case control, 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%), NNT 33, relative risk is not 0 because of continuity correction due to zero events (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%), NNT 11, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm). | |
| risk of severe case, 32.7% lower, RR 0.67, p = 0.70, treatment 2 of 14 (14.3%), control 7 of 33 (21.2%), NNT 14. | |
| [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%), NNT 20, 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%), NNT 9.2, inpatients. | |
| [Badyal], 6/7/2021, prospective, India, South Asia, peer-reviewed, 18 authors. | risk of case, 60.1% lower, RR 0.40, p < 0.001, treatment 247 of 617 (40.0%), control 611 of 1,473 (41.5%), NNT 69, adjusted per study, odds ratio converted to relative risk, >=6 weeks, logistic regression. |
| risk of case, 35.1% lower, RR 0.65, p = 0.003, treatment 88 of 185 (47.6%), control 611 of 1,473 (41.5%), adjusted per study, odds ratio converted to relative risk, 4-5 weeks, logistic regression. | |
| risk of case, 23.2% lower, RR 0.77, p = 0.04, treatment 80 of 181 (44.2%), control 611 of 1,473 (41.5%), adjusted per study, odds ratio converted to relative risk, 2-3 weeks, logistic regression. | |
| [Bae], 2/20/2021, retrospective, propensity score matching, South Korea, Asia, peer-reviewed, 8 authors. | risk of case, 30.3% lower, RR 0.70, p = 0.18, treatment 16 of 743 (2.2%), control 91 of 2,698 (3.4%), NNT 82, odds ratio converted to relative risk, PSM. |
| risk of case, 19.5% lower, RR 0.81, p = 0.50, treatment 16 of 743 (2.2%), control 91 of 2,698 (3.4%), NNT 82, odds ratio converted to relative risk, PSM, adjusted for region. | |
| risk of case, 30.3% lower, RR 0.70, p = 0.30, treatment 16 of 743 (2.2%), control 91 of 2,698 (3.4%), NNT 82, odds ratio converted to relative risk, PSM, adjusted for immunosuppresant use. | |
| risk of case, 40.2% lower, RR 0.60, p = 0.09, odds ratio converted to relative risk, PSM, HCQ >= 6 months. | |
| [Behera], 11/3/2020, retrospective, India, South Asia, peer-reviewed, 13 authors. | risk of case, 27.9% lower, RR 0.72, p = 0.29, treatment 7 of 19 (36.8%), control 179 of 353 (50.7%), NNT 7.2, adjusted per study, odds ratio converted to relative risk, model 2 conditional logistic regression. |
| risk of case, 26.3% lower, RR 0.74, p = 0.25, treatment 7 of 19 (36.8%), control 179 of 353 (50.7%), NNT 7.2, odds ratio converted to relative risk, matched pair analysis. | |
| [Bhatt], 8/4/2021, prospective, India, South Asia, preprint, 4 authors. | risk of case, 49.3% higher, RR 1.49, p = 0.02, treatment 167 of 731 (22.8%), control 30 of 196 (15.3%). |
| [Bhattacharya], 6/9/2020, retrospective, India, South Asia, preprint, 7 authors. | risk of case, 80.7% lower, RR 0.19, p = 0.001, treatment 4 of 54 (7.4%), control 20 of 52 (38.5%), NNT 3.2. |
| [Cassione], 5/12/2020, retrospective, Italy, Europe, preprint, survey, median age 52.5, 6 authors, excluded in exclusion analyses: not fully adjusting for the different baseline risk of systemic autoimmune patients. | risk of 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 case, 66.8% lower, RR 0.33, p < 0.001, treatment 12 of 68 (17.6%), control 206 of 387 (53.2%), NNT 2.8, full course vs. unused. |
| [Cordtz], 12/28/2020, retrospective, population-based cohort, Denmark, Europe, peer-reviewed, 10 authors. | risk of hospitalization, 24.0% lower, RR 0.76, p = 0.67, treatment 3 of 2,722 (0.1%), control 38 of 26,718 (0.1%), NNT 3124, adjusted per study, time-dependent exposure model. |
| risk of hospitalization, 55.0% lower, RR 0.45, p = 0.28, treatment 3 of 2,722 (0.1%), control 38 of 26,718 (0.1%), NNT 3124, adjusted per study, time-fixed exposure model. | |
| [Datta], 11/6/2020, retrospective, India, South Asia, peer-reviewed, 7 authors. | risk of case, 22.1% lower, RR 0.78, p = 0.47, treatment 16 of 146 (11.0%), control 19 of 135 (14.1%), NNT 32. |
| [de la Iglesia], 9/2/2020, retrospective, database analysis, Spain, Europe, preprint, 17 authors, excluded in exclusion analyses: not fully adjusting for the different baseline risk of systemic autoimmune patients. | 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 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 case, 7.8% lower, RR 0.92, p = 0.84, treatment 12 of 678 (1.8%), control 13 of 677 (1.9%), NNT 665, confirmed COVID-19. | |
| [Desbois], 7/20/2020, retrospective, France, Europe, preprint, mean age 58.8, 13 authors. | risk of case, 16.9% lower, RR 0.83, p = 1.00, treatment 3 of 27 (11.1%), control 23 of 172 (13.4%), NNT 44. |
| [Dev], 3/24/2021, retrospective, India, South Asia, peer-reviewed, 5 authors. | risk of case, 26.0% lower, RR 0.74, p = 0.003, treatment 260, control 499, any number of HCQ doses vs. no HCQ prophylaxis. |
| [Ferreira (B)], 6/29/2020, retrospective, population-based cohort, database analysis, Portugal, Europe, peer-reviewed, 3 authors. | risk of case, 47.1% lower, RR 0.53, p < 0.001, NNT 67, 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%), NNT 64. |
| [Fitzgerald], 2/5/2021, retrospective, USA, North America, preprint, 34 authors, excluded in exclusion analyses: not fully adjusting for the baseline risk differences within systemic autoimmune patients. | risk of case, 8.5% lower, RR 0.91, p = 0.54, treatment 65 of 1,072 (6.1%), control 200 of 3,594 (5.6%), adjusted per study, odds ratio converted to relative risk. |
| [Fung], 10/1/2021, retrospective, population-based cohort, USA, North America, preprint, 6 authors, excluded in exclusion analyses: not fully adjusting for the different baseline risk of systemic autoimmune patients. | risk of death, 15.0% lower, RR 0.85, p = 0.10, vs. past use (better match for systemic autoimmune diseases). |
| risk of hospitalization, 5.0% lower, RR 0.95, p = 0.41, vs. past use (better match for systemic autoimmune diseases). | |
| risk of case, 10.0% lower, RR 0.90, p = 0.004, vs. past use (better match for systemic autoimmune diseases). | |
| risk of death, 6.0% higher, RR 1.06, p = 0.39, vs. never used. | |
| risk of hospitalization, 4.0% higher, RR 1.04, p = 0.32, vs. never used. | |
| risk of case, 5.0% lower, RR 0.95, p = 0.06, vs. never used. | |
| [Gendebien], 6/25/2020, retrospective, Belgium, Europe, preprint, survey, 9 authors, excluded in exclusion analyses: not fully adjusting for the baseline risk differences within systemic autoimmune patients. | risk of case, 3.9% lower, RR 0.96, p = 0.93, treatment 12 of 152 (7.9%), control 6 of 73 (8.2%), NNT 308. |
| [Gendelman], 5/5/2020, retrospective, database analysis, Israel, Middle East, peer-reviewed, 5 authors, excluded in exclusion analyses: not fully adjusting for the different baseline risk of systemic autoimmune patients. | risk of case, 8.1% lower, RR 0.92, p = 0.88, treatment 3 of 36 (8.3%), control 1,314 of 14,484 (9.1%), NNT 135. |
| [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 10,703 (0.0%), control 7 of 21,406 (0.0%), NNT 3058, relative risk is not 0 because of continuity correction due to zero events (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%), NNT 11, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), mortality for infected patients. | |
| risk of case, 20.9% lower, RR 0.79, p = 0.27, treatment 31 of 10,703 (0.3%), control 78 of 21,406 (0.4%), NNT 1338, odds ratio converted to relative risk. | |
| [Gianfrancesco], 5/28/2020, retrospective, database analysis, multiple countries, multiple regions, peer-reviewed, 28 authors, excluded in exclusion analyses: not fully adjusting for the baseline risk differences within systemic autoimmune patients. | risk of hospitalization, 3.3% lower, RR 0.97, p = 0.82, treatment 58 of 130 (44.6%), control 219 of 470 (46.6%), NNT 50, 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%), NNT 8.6, adjusted per study, odds ratio converted to relative risk. |
| [Grau-Pujol], 9/21/2020, Randomized Controlled Trial, Spain, Europe, peer-reviewed, 22 authors. | risk of case, 10.6% lower, RR 0.89, p = 1.00, treatment 1 of 142 (0.7%), control 1 of 127 (0.8%), NNT 1202. |
| [Gönenli], 12/16/2020, retrospective, Turkey, Europe, 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%), NNT 117. |
| risk of 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, excluded in exclusion analyses: significant unadjusted confounding possible. | risk of hospitalization, 80.0% lower, RR 0.20, p < 0.001, treatment 8, control 1,247. |
| [Huh], 12/19/2020, retrospective, database analysis, South Korea, Asia, peer-reviewed, 8 authors, excluded in exclusion analyses: not fully adjusting for the different baseline risk of systemic autoimmune patients. | risk of progression, 251.0% higher, RR 3.51, p = 0.11, treatment 5 of 8 (62.5%), control 873 of 2,797 (31.2%), adjusted per study, multivariate. |
| risk of case, 6.0% lower, RR 0.94, p = 0.82, treatment 17 of 122 (13.9%), control 7,324 of 43,924 (16.7%), NNT 36, adjusted per study, multivariate. | |
| [Huh (B)], 5/4/2020, retrospective, case control, database analysis, South Korea, Asia, preprint, 10 authors, excluded in exclusion analyses: not fully adjusting for the different baseline risk of systemic autoimmune patients. | risk of 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 1,417 (0.1%), NNT 1417, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm). |
| risk of case, 13.1% higher, RR 1.13, p = 0.86, treatment 15 of 649 (2.3%), control 31 of 1,417 (2.2%), adjusted per study. | |
| [Kadnur], 7/22/2020, prospective, India, South Asia, preprint, 26 authors. | risk of case, 86.3% lower, RR 0.14, p = 0.03, treatment 2 of 248 (0.8%), control 5 of 86 (5.8%), NNT 20, odds ratio converted to relative risk, multivariate logistic regression. |
| [Kamstrup], 6/1/2021, retrospective, population-based cohort, Denmark, Europe, peer-reviewed, 21 authors, excluded in exclusion analyses: not fully adjusting for the different baseline risk of systemic autoimmune patients. | risk of hospitalization, 44.0% higher, RR 1.44, p = 0.25, treatment 5,488, control 54,846, RR approximated with OR. |
| risk of case, 10.0% lower, RR 0.90, p = 0.23, treatment 188 of 5,488 (3.4%), control 2,040 of 54,846 (3.7%), NNT 340, adjusted Cox proportional hazards regression. | |
| [Khurana], 7/24/2020, retrospective, India, South Asia, preprint, survey, 5 authors. | risk of case, 51.0% lower, RR 0.49, p = 0.02, treatment 6 of 22 (27.3%), control 88 of 159 (55.3%), NNT 3.6, odds ratio converted to relative risk. |
| [Konig], 5/7/2020, retrospective, database analysis, multiple countries, multiple regions, preprint, 11 authors, excluded in exclusion analyses: not fully adjusting for the baseline risk differences within systemic autoimmune patients. | risk of hospitalization, 3.0% lower, RR 0.97, p = 0.88, treatment 16 of 29 (55.2%), control 29 of 51 (56.9%), NNT 59. |
| [Korkmaz], 6/1/2021, retrospective, Turkey, Europe, preprint, 4 authors. | risk of death, 82.1% lower, RR 0.18, p = 0.19, treatment 0 of 385 (0.0%), control 2 of 299 (0.7%), NNT 150, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm). |
| risk of case, 93.7% lower, RR 0.06, p < 0.001, treatment 2 of 395 (0.5%), control 24 of 299 (8.0%), NNT 13. | |
| [Küçükakkaş], 7/20/2021, retrospective, Turkey, Europe, preprint, 2 authors, excluded in exclusion analyses: minimal details of groups provided. | risk of ICU admission, 42.9% higher, RR 1.43, p = 1.00, treatment 1 of 7 (14.3%), control 1 of 10 (10.0%). |
| [Laplana], 9/9/2020, retrospective, Spain, Europe, peer-reviewed, survey, 3 authors, excluded in exclusion analyses: not fully adjusting for the different baseline risk of systemic autoimmune patients. | risk of 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, excluded in exclusion analyses: not fully adjusting for the baseline risk differences within systemic autoimmune patients. | risk of hospitalization, 25.5% lower, RR 0.74, p = 1.00, treatment 1 of 290 (0.3%), control 2 of 432 (0.5%), NNT 846. |
| risk of 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 case, 89.5% lower, RR 0.10, p < 0.001, treatment 10 of 491 (2.0%), control 22 of 113 (19.5%), NNT 5.7. |
| risk of case, 88.5% lower, RR 0.12, p < 0.001, treatment 5 of 491 (1.0%), control 10 of 113 (8.8%), NNT 13, symptomatic. | |
| [McKinnon], 12/23/2021, Double Blind Randomized Controlled Trial, USA, North America, peer-reviewed, 10 authors. | risk of symptomatic case, 2.5% lower, RR 0.98, p = 1.00, treatment 2 of 365 (0.5%), control 1 of 178 (0.6%), NNT 7219, daily and weekly HCQ combined. |
| risk of symptomatic case, no change, RR 1.00, p = 1.00, treatment 1 of 178 (0.6%), control 1 of 178 (0.6%), daily HCQ. | |
| risk of symptomatic case, 4.8% lower, RR 0.95, p = 1.00, treatment 1 of 187 (0.5%), control 1 of 178 (0.6%), NNT 3698, weekly HCQ. | |
| risk of symptomatic case, 53.3% lower, RR 0.47, p = 1.00, treatment 0 of 25 (0.0%), control 1 of 178 (0.6%), NNT 178, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), AD patients. | |
| risk of case, 51.2% lower, RR 0.49, p = 0.60, treatment 2 of 365 (0.5%), control 2 of 178 (1.1%), NNT 174, daily and weekly HCQ combined. | |
| risk of case, 50.0% lower, RR 0.50, p = 1.00, treatment 1 of 178 (0.6%), control 2 of 178 (1.1%), NNT 178, daily HCQ. | |
| risk of case, 52.4% lower, RR 0.48, p = 0.61, treatment 1 of 187 (0.5%), control 2 of 178 (1.1%), NNT 170, weekly HCQ. | |
| risk of case, 69.5% lower, RR 0.30, p = 1.00, treatment 0 of 25 (0.0%), control 2 of 178 (1.1%), NNT 89, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), AD patients. | |
| [Mitchell], 5/5/2020, retrospective, multiple countries, multiple regions, preprint, 2 authors, excluded in exclusion analyses: excessive unadjusted differences between groups. | risk of death, 99.0% lower, RR 0.01, p < 0.001. |
| [Naggie], 8/25/2021, Randomized Controlled Trial, USA, North America, preprint, 22 authors. | risk of symptomatic case, 23.5% lower, RR 0.76, p = 0.18, treatment 41 of 683 (6.0%), control 53 of 676 (7.8%), NNT 54, odds ratio converted to relative risk, logistic regression. |
| risk of symptomatic case, 29.3% lower, RR 0.71, p = 0.18, treatment 41 of 683 (6.0%), control 53 of 676 (7.8%), NNT 54, odds ratio converted to relative risk, Mantel–Haenszel. | |
| [Patil], 8/24/2021, prospective, India, South Asia, preprint, 20 authors. | risk of death, 65.9% lower, RR 0.34, p = 0.10, treatment 5,266, control 3,946. |
| risk of case, 9.1% lower, RR 0.91, p = 0.43, treatment 167 of 5,266 (3.2%), control 147 of 3,946 (3.7%), NNT 181, adjusted per study. | |
| [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%), NNT 28, 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%), NNT 987. |
| risk of case, 27.0% lower, RR 0.73, p = 0.12, treatment 58 of 989 (5.9%), control 39 of 494 (7.9%), NNT 49. | |
| [Rangel], 1/10/2021, retrospective, USA, North America, peer-reviewed, 5 authors, excluded in exclusion analyses: not fully adjusting for the different baseline risk of systemic autoimmune patients. | risk of death, 25.1% lower, RR 0.75, p = 0.77, treatment 4 of 50 (8.0%), control 11 of 103 (10.7%), NNT 37, 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%), NNT 10. | |
| hospitalization time, 41.2% lower, relative time 0.59, p = 0.12, treatment 21, control 54. | |
| [Rao], 12/4/2021, prospective, India, South Asia, peer-reviewed, 8 authors, excluded in exclusion analyses: unadjusted results with minimal group details. | risk of case, 11.0% lower, RR 0.89, p = 0.68, treatment 16 of 273 (5.9%), control 67 of 1,021 (6.6%), NNT 143. |
| [Rentsch], 9/9/2020, retrospective, population-based cohort, database analysis, United Kingdom, Europe, peer-reviewed, 34 authors, excluded in exclusion analyses: not fully adjusting for the baseline risk differences within systemic autoimmune patients, medication adherence unknown and may significantly change results. | risk of death, 3.0% higher, RR 1.03, p = 0.83, treatment 70 of 30,569 (0.2%), control 477 of 164,068 (0.3%), NNT 1620, adjusted per study. |
| [Revollo], 11/21/2020, retrospective, propensity score matching, Spain, Europe, peer-reviewed, 16 authors. | risk of 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 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+. | |
| [Rojas-Serrano], 5/16/2021, Double Blind Randomized Controlled Trial, Mexico, North America, preprint, 8 authors. | risk of symptomatic case, 82.0% lower, RR 0.18, p = 0.12, treatment 1 of 62 (1.6%), control 6 of 65 (9.2%), NNT 13, adjusted per study. |
| [Salvarani], 8/6/2020, retrospective, population-based cohort, Italy, Europe, peer-reviewed, 18 authors, excluded in exclusion analyses: not fully adjusting for the different baseline risk of systemic autoimmune patients. | risk of case, 6.0% lower, RR 0.94, p = 0.75, RR approximated with OR. |
| [Samajdar], 11/17/2021, retrospective, India, South Asia, peer-reviewed, 9 authors, 1 September, 2020 - 31 December, 2020, dosage not specified, excluded in exclusion analyses: minimal details provided, unadjusted results with no group details, results may be significantly affected by survey bias. | risk of case, 74.5% lower, RR 0.25, p < 0.001, treatment 12 of 129 (9.3%), control 29 of 81 (35.8%), NNT 3.8, odds ratio converted to relative risk, physician survey. |
| risk of case, 48.6% lower, RR 0.51, p = 0.03, treatment 11 of 109 (10.1%), control 39 of 200 (19.5%), NNT 11, odds ratio converted to relative risk, combined ivermectin or HCQ in community. | |
| [Singer], 8/5/2020, retrospective, database analysis, USA, North America, preprint, 3 authors, excluded in exclusion analyses: not fully adjusting for the baseline risk differences within systemic autoimmune patients. | risk of case, 9.0% higher, RR 1.09, p = 0.62, treatment 55 of 10,700 (0.5%), control 104 of 22,058 (0.5%). |
| [Syed], 5/17/2021, Randomized Controlled Trial, Pakistan, South Asia, preprint, 9 authors. | risk of symptomatic case, 59.7% higher, RR 1.60, p = 0.41, treatment 10 of 48 (20.8%), control 6 of 46 (13.0%), group 1. |
| risk of symptomatic case, 110.5% higher, RR 2.10, p = 0.13, treatment 14 of 51 (27.5%), control 6 of 46 (13.0%), group 2. | |
| risk of symptomatic case, 16.4% lower, RR 0.84, p = 0.77, treatment 6 of 55 (10.9%), control 6 of 46 (13.0%), NNT 47, group 3. | |
| risk of case, 6.2% lower, RR 0.94, p = 1.00, treatment 3 of 48 (6.2%), control 3 of 45 (6.7%), NNT 240, group 1. | |
| risk of case, 6.2% lower, RR 0.94, p = 1.00, treatment 3 of 48 (6.2%), control 3 of 45 (6.7%), NNT 240, group 2. | |
| risk of case, 72.2% lower, RR 0.28, p = 0.33, treatment 1 of 54 (1.9%), control 3 of 45 (6.7%), NNT 21, group 3. | |
| [Trefond], 1/27/2021, retrospective, France, Europe, peer-reviewed, 21 authors, excluded in exclusion analyses: not fully adjusting for the different baseline risk of systemic autoimmune patients, significant unadjusted confounding possible, excessive unadjusted differences between groups. | risk of death, 16.6% higher, RR 1.17, p = 0.80, treatment 4 of 68 (5.9%), control 12 of 183 (6.6%), NNT 148, adjusted per study, odds ratio converted to relative risk. |
| risk of 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, excluded in exclusion analyses: not fully adjusting for the different baseline risk of systemic autoimmune patients. | risk of hospitalization, 46.0% higher, RR 1.46, p = 0.10, treatment 40 of 6,746 (0.6%), control 50 of 13,492 (0.4%), adjusted per study. |
| risk of case, 8.0% higher, RR 1.08, p = 0.50, treatment 97 of 6,746 (1.4%), control 183 of 13,492 (1.4%), adjusted per study. | |
| [Yadav], 9/30/2020, retrospective, India, South Asia, preprint, 11 authors. | risk of hospitalization, 82.4% lower, RR 0.18, p = 0.01, treatment 2 of 279 (0.7%), control 9 of 221 (4.1%), NNT 30, PCR+. |
| risk of IgG+, 41.8% lower, RR 0.58, p = 0.05, treatment 17 of 178 (9.6%), control 27 of 221 (12.2%), NNT 38, odds ratio converted to relative risk, multivariate logistic regression. | |
| risk of IgG+, 79.0% lower, RR 0.21, p = 0.09, treatment 1 of 39 (2.6%), control 27 of 221 (12.2%), NNT 10, HCQ >10 weeks. | |
| risk of IgG+, 52.4% lower, RR 0.48, p = 0.14, treatment 5 of 86 (5.8%), control 27 of 221 (12.2%), NNT 16, HCQ 6-10 weeks. | |
| risk of IgG+, 69.9% higher, RR 1.70, p = 0.12, treatment 11 of 53 (20.8%), control 27 of 221 (12.2%), HCQ <6 weeks. | |
| [Zhong (B)], 7/3/2020, retrospective, database analysis, China, Asia, peer-reviewed, 20 authors. | risk of case, 91.0% lower, RR 0.09, p = 0.04, treatment 7 of 16 (43.8%), control 20 of 27 (74.1%), NNT 3.3, adjusted per study. |
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 pooled analysis, which may differ from the effect a paper
focuses on. Other outcomes are used in outcome specific analyses.
| [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 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 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 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 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 case, 19.0% lower, RR 0.81, p = 0.23, treatment 82 of 387 (21.2%), control 99 of 393 (25.2%), NNT 25, 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 case, 17.0% lower, RR 0.83, p = 0.35, treatment 49 of 414 (11.8%), control 58 of 407 (14.3%), NNT 41. |
| risk of case, 25.1% lower, RR 0.75, p = 0.22, treatment 32 of 414 (7.7%), control 42 of 407 (10.3%), NNT 39, probable COVID-19 cases. | |
| [Dhibar], 11/6/2020, prospective, India, South Asia, peer-reviewed, 13 authors. | risk of case, 41.0% lower, RR 0.59, p = 0.03, treatment 14 of 132 (10.6%), control 36 of 185 (19.5%), NNT 11, adjusted per study. |
| risk of case, 50.0% lower, RR 0.50, p = 0.04, treatment 10 of 132 (7.6%), control 28 of 185 (15.1%), NNT 13, 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%), NNT 28, 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 1,196 (0.3%), control 9 of 1,301 (0.7%), NNT 280, 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 1,196 (1.1%), control 18 of 1,301 (1.4%), NNT 337, 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 1,042 (4.3%), NNT 77. | |
| [Polat], 9/30/2020, prospective, Turkey, Europe, peer-reviewed, 3 authors. | risk of case, 57.0% lower, RR 0.43, p = 0.03, treatment 12 of 138 (8.7%), control 14 of 70 (20.0%), NNT 8.8. |
| [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 severe case, 35.1% lower, RR 0.65, p = 0.14, treatment 29 of 432 (6.7%), control 64 of 619 (10.3%), NNT 28. |
| risk of case, 32.0% lower, RR 0.68, p = 0.009, treatment 212 of 432 (49.1%), control 433 of 619 (70.0%), NNT 4.8, adjusted per study, odds ratio converted to relative risk, model 6. | |
| [Shabani], 8/10/2021, prospective, Iran, Middle East, peer-reviewed, 16 authors. | risk of symptomatic case, 19.0% lower, RR 0.81, p = 1.00, treatment 2 of 51 (3.9%), control 3 of 62 (4.8%), NNT 109, day 7. |
| risk of case, 6.4% higher, RR 1.06, p = 1.00, treatment 7 of 51 (13.7%), control 8 of 62 (12.9%), day 7, PCR+ and symptomatic. | |
| risk of case, 21.6% higher, RR 1.22, p = 0.78, treatment 7 of 51 (13.7%), control 7 of 62 (11.3%), day 7, PCR+ only. | |
| [Simova (B)], 11/12/2020, retrospective, Bulgaria, Europe, peer-reviewed, 5 authors. | risk of case, 92.7% lower, RR 0.07, p = 0.01, treatment 0 of 156 (0.0%), control 3 of 48 (6.2%), NNT 16, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm). |
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https://guardian.ng/news/nigeria/n..r-covid-19-prevention-says-nafdac/.
The Indian Express,
Vadodara administration drive: HCQ helping in containing Covid-19 cases, say docs as analysis begins,
https://indianexpress.com/article/..y-docs-as-analysis-begins-6486049/.
The Moscow Times,
Russia Approves Unproven Malaria Drug to Treat Coronavirus,
https://www.themoscowtimes.com/202..a-drug-to-treat-coronavirus-a70025.
The New York Times,
Malaria Drug Taken by Trump Is Tied to Increased Risk of Heart Problems and Death in New Study,
https://www.nytimes.com/2020/05/22..alaria-drug-trump-coronavirus.html.
The New York Times (B),
Small Chloroquine Study Halted Over Risk of Fatal Heart Complications,
https://www.nytimes.com/2020/04/12..ronavirus-trump.html?smid=em-share.
The New York Times (C),
Malaria Drug Promoted by Trump Did Not Prevent Covid Infections, Study Finds,
https://www.nytimes.com/2020/06/03..chloroquine-coronavirus-trump.html.
The New York Times (D),
Coronavirus Can Be Deadly for Young Adults, Too, Study Finds,
https://www.nytimes.com/2020/09/10/world/covid-19-coronavirus.html.
The North Africa Post,
Morocco continues use of Chloroquine despite controversy,
https://northafricapost.com/41247-..loroquine-despite-controversy.html.
The Tico Times,
News briefs: Reopening plans on-track, hydroxychloroquine use to continue, partnership with Coursera,
https://ticotimes.net/2020/06/15/n..continue-partnership-with-coursera.
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Turrini et al., Vaccines, 10.3390/vaccines9060640,
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Ubaldo et al., Critical Care Research and Practice, 10.1155/2021/7510306,
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Ukrinform,
Ukraine receives batch of hydroxychloroquine tablets from India,
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Vanguard,
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Voice of America,
Cameroon Begins Large-scale Chloroquine Production,
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Please send us corrections, updates, or comments. Vaccines and treatments are both extremely valuable and complementary. All
practical, effective, and safe means should be used. Elimination of COVID-19
is a race against viral evolution. No treatment, vaccine, or intervention is
100% available and effective for all current and future variants. Denying the
efficacy of any method increases the risk of COVID-19 becoming endemic; and
increases mortality, morbidity, and collateral damage. We do not provide
medical advice. Before taking any medication, consult a qualified physician
who can provide personalized advice and details of risks and benefits based
on your medical history and situation. Treatment protocols for physicians are
available from the FLCCC.