https://hcqmeta.com/
•Meta analysis using the most serious
outcome reported shows 63% [53‑70%] improvement for the
38 early
treatment studies. Results are similar after exclusion based sensitivity
analysis and after restriction to peer-reviewed studies. The
11 RCTs
show 39% [8‑59%] improvement, and the
15 mortality
results shows 72% [57‑81%] lower mortality.
•21 early treatment
studies show statistically significant improvements in isolation
(15 for the most serious outcome).
•Late treatment is less successful,
with only 67% of the
231 studies reporting a positive effect. Very
late stage treatment is not effective and may be harmful, especially when
using excessive dosages.
•78% 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
0.0053.
•There is evidence of bias towards publishing negative results.
76% of prospective studies report positive
effects, compared to 71% of retrospective
studies. Studies from North America
are 2.7
times more likely to report negative results than studies from the rest of the
world combined, p = 0.0000000103.
•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.
Multiple treatments are typically used in
combination, which may be significantly more effective.
•No treatment, vaccine, or intervention is 100%
available and effective for all variants. All practical, effective, and safe
means should be used.
Denying the efficacy of treatments increases mortality, morbidity, collateral
damage, and endemic risk.
•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 | 343 studies | 5,419 authors | 458,586 patients |
| Positive effects | 248 studies | 3,834 authors | 329,335 patients |
| Early treatment | 63% improvement | RR 0.37 [0.30-0.47] |
| Late treatment | 19% improvement | RR 0.81 [0.76-0.85] |
Highlights
HCQ reduces
risk for COVID-19 with very high confidence for mortality, hospitalization, cases, viral clearance, and in pooled analysis.
We show traditional outcome specific analyses and combined
evidence from all studies, incorporating treatment delay, a primary
confounding factor in COVID-19 studies.
Real-time updates and corrections,
transparent analysis with all results in the same format, consistent protocol
for 42
treatments.
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 and C. Random effects
meta-analysis of all early treatment mortality and hospitalization results.
D. Scatter plot of the effects reported in early treatment studies and
in all studies. Early treatment is more effective. E and F.
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.
Preclinical and Phase I Research
5 In Silico studies support the efficacy of hydroxychloroquine [Baildya, Hussein, Noureddine, Tarek, Yadav].
13 In Vitro studies support the efficacy of hydroxychloroquine [Andreani, Clementi, Dang, Delandre, Faísca, Hoffmann, Liu, Ou, Purwati, Sheaff, Wang, Wang (B), Yao].
An In Vivo animal study supports the efficacy of hydroxychloroquine [Maisonnasse].
3 studies investigate novel formulations of hydroxychloroquine that may be more
effective for COVID-19 [Faísca, Klimke, Zelenko].
[Kavanagh] present a phase I clinical study investigating a
novel formulation of hydroxychloroquine that may be more effective for COVID-19.
Preclinical research is an important part of the development of
treatments, however results may be very different in clinical trials.
Preclinical results are not used in this paper.
Results
Figure 3 shows a visual overview of the results.
Figure 4, Figure 5, and
Table 1 show results by treatment stage, and Figure 6
shows a forest plot for a random effects meta-analysis of all studies.
Figure 7 and Figure 8 show forest plots restricted to mortality
and hospitalization results only.
Early treatment.
92% of early treatment studies
report a positive effect, with an estimated reduction of
63% in the effect measured
(death, hospitalization, etc.) from the random effects meta-analysis, RR
0.37
[0.30-0.47].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.Figure 3. Overview of results.
| 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 | 35 | 38 | 92.1% | 1 in 30 million |
63% improvement RR 0.37 [0.30‑0.47] p < 0.0001 |
| Late treatment | 156 | 232 | 67.2% | 1 in 12 million |
19% improvement RR 0.81 [0.76‑0.85] p < 0.0001 |
| Pre‑Exposure Prophylaxis | 55 | 71 | 77.5% | 1 in 533 thousand |
32% improvement RR 0.68 [0.58‑0.79] p < 0.0001 |
| Post‑Exposure Prophylaxis | 7 | 8 | 87.5% | 1 in 28 |
33% improvement RR 0.67 [0.53‑0.84] p = 0.0005 |
| All studies | 248 | 343 | 72.3% | 1 in 29 quadrillion |
25% improvement RR 0.75 [0.71‑0.79] p < 0.0001 |
Table 1. Results by treatment stage.
6 studies report results for a subset with early
treatment, these are not included in the overall results.
Figure 4. Results by treatment stage.
Figure 5. 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 6. 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 7. 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 8. 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 9, Figure 10, 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
27%
improvement in random effects meta-analysis, RR
0.73
[0.61‑0.88],
p = 0.00079. Early treatment RCTs show
39% improvement,
RR 0.61
[0.41‑0.92],
p = 0.018.
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 9. 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.
Figure 10. RCTs excluding late treatment. 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. C. 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 |
| Randomized Controlled Trials | 36 | 53 | 67.9% | 1 in 158 |
19% improvement RR 0.81 [0.69‑0.95] p = 0.01 |
| Randomized Controlled Trials (excluding late treatment) | 18 | 23 | 78.3% | 1 in 188 |
27% improvement RR 0.73 [0.61‑0.88] p = 0.00079 |
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 11.
[Ader], very late stage, >50% on oxygen/ventilation at baseline.
[Alamdari], substantial unadjusted confounding by indication likely.
[Albanghali], unadjusted results with no group details, substantial unadjusted confounding by indication likely.
[Albani], substantial unadjusted confounding by indication likely, substantial confounding by time 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 at baseline.
[Alhamlan], substantial unadjusted confounding by indication likely, substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
[Alwafi], excessive unadjusted differences between groups.
[Annie], confounding by indication is likely and adjustments do not consider COVID-19 severity at baseline.
[Aparisi], unadjusted results with no group details.
[Awad], substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely.
[Azaña Gómez], unadjusted results with no group details.
[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.
[Cortez], 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.
[Erden], unadjusted results with no group details.
[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 confounding by time 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.
[Hall], unadjusted results with no group details.
[Hraiech], very late stage, ICU patients.
[Huang], significant unadjusted confounding possible.
[Huh], 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 confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
[Juneja], excessive unadjusted differences between groups.
[Kamran], excessive unadjusted differences between groups.
[Kamstrup], not fully adjusting for the different baseline risk of systemic autoimmune patients.
[Karruli], unadjusted results with no group details.
[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 confounding by time 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 confounding by time 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.
[Mahale], unadjusted results with no group details.
[Mahto], unadjusted results with no group details.
[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 confounding by time 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 confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
[Niwas], excessive unadjusted differences between groups.
[Oztas], not adjusting for the different baseline risk of systemic autoimmune patients, excessive unadjusted differences between groups.
[Pasquini], unadjusted results with no group details.
[Peters], excessive unadjusted differences between groups.
[Psevdos], unadjusted results with no group details, no treatment details, substantial confounding by time 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 confounding by time 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.
[Rosenthal], confounding by indication is likely and adjustments do not consider COVID-19 severity at baseline.
[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.
[Salehi], unadjusted results with no group details.
[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 confounding by time 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.
[Schmidt], confounding by indication is likely and adjustments do not consider COVID-19 severity at baseline.
[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 at baseline.
[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], unadjusted results with no group details, substantial unadjusted confounding by indication likely, substantial confounding by time possible due to significant changes in SOC and treatment propensity near the start of the pandemic.
[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 confounding by time 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 confounding by time 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 confounding by time 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 confounding by time 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 confounding by time 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 confounding by time 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 confounding by time 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.
[Tamura], substantial unadjusted confounding by indication likely, substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
[Tehrani], substantial unadjusted confounding by indication likely, unadjusted results with no group details.
[Texeira], unadjusted results with no group details, no treatment details, substantial confounding by time 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 confounding by time 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 (C)], confounding by indication is likely and adjustments do not consider COVID-19 severity at baseline.
[Xia], minimal details provided.
[Yegerov], unadjusted results with no group details.
[Çivriz Bozdağ], substantial confounding by time 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 11. 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 an antiviral may be very effective when used
early but may not be effective in late stage disease, and may even be harmful.
Oseltamivir, for example, is generally only considered effective for influenza
when used within 0-36 or 0-48 hours [McLean, Treanor].
Figure 12 shows a mixed-effects meta-regression of efficacy as
a function of treatment delay in HCQ COVID-19 studies, showing that efficacy declines rapidly with treatment delay.
Early treatment is critical for COVID-19.
Figure 12. Meta-regression
showing efficacy as a function of treatment delay in COVID-19 HCQ studies. Early
treatment is critical.
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 (as in [López-Medina]).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 many different
variants of SARS-CoV-2 and efficacy may depend critically on the distribution
of variants encountered by the patients in a study. For example, the Gamma
variant shows significantly different characteristics
[Faria, Karita, Nonaka, Zavascki]. Different mechanisms of action may be
more or less effective depending on variants, for example the viral entry
process for the omicron variant has moved towards TMPRSS2-independent fusion,
suggesting that TMPRSS2 inhibitors may be less effective
[Peacock, Willett].Regimen.
Effectiveness may depend strongly on the dosage and treatment regimen.
Treatments.
The use of other
treatments may significantly affect outcomes, including anything from
supplements, other medications, 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 very 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, important to avoid cherry-picking,
and informative when a positive result is found despite combining less-optimal
situations. However, 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, 75.6% of prospective
studies report positive effects, compared to
71.2% of retrospective studies, suggesting a
bias toward publishing negative results. The median effect size for
prospective studies is 27% improvement,
compared to 23% for retrospective
studies. Figure 13 shows a scatter plot of results for prospective
and retrospective studies.
Figure 14 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,
53.2% vs. 20.0%,
two-tailed z test -5.73, p =
0.0000000103. [Berry] performed an independent analysis
which also showed bias toward negative results for US-based research.
Figure 13. Prospective vs. retrospective studies.
Figure 15. 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 248 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].
Physician case series results.
Table 3 shows the reported results of physicians that use early
treatments for COVID-19, compared to the results for a non-treating physician
(this physician reportedly prescribed early treatment for themself, but not
for patients [medicospelavidacovid19.com.br]). The treatments used vary between physicians. Almost
all report using ivermectin and/or HCQ, and most use additional treatments in
combination. A more detailed analysis requires information on the patient
populations, however results are consistent with the extensive controlled
trial evidence that shows a significant reduction in risk with early
treatments, and improved results with the use of multiple treatments.| LATE TREATMENT | ||||||
| Physician / Team | Location | Patients | HospitalizationHosp. | MortalityDeath | ||
| Dr. David Uip (*) | Brazil | 2,200 | 38.6% (850) | Ref. | 2.5% (54) | Ref. |
| EARLY TREATMENT | ||||||
| Physician / Team | Location | Patients | HospitalizationHosp. | ImprovementImp. | MortalityDeath | ImprovementImp. |
| Dr. Edimilson Migowski | Brazil | 2,000 | 0.3% (7) | 99.1% | 0.1% (2) | 95.9% |
| Dr. Bryan Tyson & Dr. George Fareed | USA | 4,375 | 0.2% (9) | 99.5% | 0.1% (3) | 97.2% |
| Dr. Flavio Cadegiani | Brazil | 3,450 | 0.1% (4) | 99.7% | 0.0% (0) | 100.0% |
| Dr. Brian Proctor | USA | 869 | 2.3% (20) | 94.0% | 0.2% (2) | 90.6% |
| Dr. Didier Raoult | France | 8,315 | 2.6% (214) | 93.3% | 0.1% (5) | 97.6% |
| Dr. Anastacio Queiroz | Brazil | 700 | 0.0% (0) | 100.0% | ||
| Dr. Ellen Guimarães | Brazil | 500 | 1.6% (8) | 95.9% | 0.4% (2) | 83.7% |
| Dr. Ben Marble | USA | 150,000 | 0.0% (4) | 99.9% | ||
| Dr. Vladimir Zelenko | USA | 2,200 | 0.5% (12) | 98.6% | 0.1% (2) | 96.3% |
| Dr. Vipul Shah | India | 8,000 | 0.1% (5) | 97.5% | ||
| Dr. Shankara Chetty | South Africa | 8,000 | 0.0% (0) | 100.0% | ||
| Dr. Ryan Cole | USA | 400 | 0.0% (0) | 100.0% | 0.0% (0) | 100.0% |
| Dr. Roberta Lacerda | Brazil | 550 | 1.5% (8) | 96.2% | 0.4% (2) | 85.2% |
| Dr. Carlos Nigro | Brazil | 5,000 | 0.9% (45) | 97.7% | 0.5% (23) | 81.3% |
| Dr. Abdulrahman Mohana | Saudi Arabia | 2,733 | 0.0% (0) | 100.0% | ||
| Dr. Oluwagbenga Alonge | Nigeria | 310 | 0.0% (0) | 100.0% | ||
| Dr. Roman Rozencwaig patients up to 86 years old |
Canada | 80 | 0.0% (0) | 100.0% | ||
| Dr. Heather Gessling | USA | 1,500 | 0.1% (1) | 97.3% | ||
| Dr. Deborah Chisholm | USA | 100 | 0.0% (0) | 100.0% | ||
| Dr. Karin Ried up to 99yo, 73% comorbidities, av. age 63 |
Turkey | 237 | 0.4% (1) | 82.8% | ||
| Dr. Raja Bhattacharya up to 88yo, 81% comorbidities |
India | 148 | 1.4% (2) | 44.9% | ||
| Dr. Mohammed Tarek Alam patients up to 84 years old |
Bangladesh | 100 | 0.0% (0) | 100.0% | ||
| Dr. Roberto Alfonso Accinelli 0/360 deaths for treatment within 3 days |
Peru | 1,265 | 0.6% (7) | 77.5% | ||
| Dr. Mark Hancock | USA | 24 | 0.0% (0) | 100.0% | ||
| Dr. Syed Haider | USA | 4,000 | 0.1% (5) | 99.7% | 0.0% (0) | 100.0% |
| Dr. Benoit Ochs | Luxembourg | 8,000 | 0.0% (0) | 100.0% | ||
| Dr. Mollie James | USA | 3,500 | 1.1% (40) | 97.0% | 0.0% (1) | 98.8% |
| Dr. Dhanajay | India | 500 | 0.0% (0) | 100.0% | ||
| Mean improvement | 219,056 | HospitalizationHosp. | 97.6% | MortalityDeath | 93.8% | |
Table 3. Physician results with early treatment protocols compared to
no early treatment. (*) Dr. Uip reportedly prescribed early
treatment for himself, but not for patients [medicospelavidacovid19.com.br].
Funnel plot analysis.
Funnel
plots have traditionally been used for analyzing publication bias. This is
invalid for COVID-19 acute treatment trials — the underlying assumptions
are invalid, which we can demonstrate with a simple example. Consider a set of
hypothetical perfect trials with no bias. Figure 16 plot A
shows a funnel plot for a simulation of 80 perfect trials, with random group
sizes, and each patient's outcome randomly sampled (10% control event
probability, and a 30% effect size for treatment). Analysis shows no asymmetry
(p > 0.05). In plot B, we add a single typical variation in COVID-19 treatment
trials — treatment delay. Consider that efficacy varies from 90% for
treatment within 24 hours, reducing to 10% when treatment is delayed 3 days.
In plot B, each trial's treatment delay is randomly selected. Analysis now
shows highly significant asymmetry, p < 0.0001, with six variants of
Egger's test all showing p < 0.05
[Egger, Harbord, Macaskill, Moreno, Peters (B), Rothstein, Rücker, Stanley].
Note that these tests fail even though treatment delay is uniformly
distributed. In reality treatment delay is more complex — each trial has
a different distribution of delays across patients, and the distribution
across trials may be biased (e.g., late treatment trials may be more common).
Similarly, many other variations in trials may produce asymmetry, including
dose, administration, duration of treatment, differences in SOC,
comorbidities, age, variants, and bias in design, implementation, analysis,
and reporting.
Figure 16. Example funnel plot analysis for
simulated perfect trials.
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. 92% of early
treatment studies report a positive effect, with an estimated reduction of
63% in the effect measured
(death, hospitalization, etc.) in the random effects meta-analysis, RR
0.37
[0.30-0.47]. 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 38 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 63% [53‑70%] improvement for the 38 early treatment studies. Results are
similar after exclusion based sensitivity analysis and after restriction to
peer-reviewed studies. Restricting to the 11 RCTs
shows 39% [8‑59%] improvement, and restricting to the 15 mortality
results shows 72% [57‑81%] 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/.
5/11: We added [Niwas].
5/9: We added [Uyaroğlu].
5/6: We added [Hong].
5/3: We updated [Kadnur] to the journal version.
5/2: We added [MacFadden].
4/17: We added a section on preclinical research.
4/16: We added [Roy-García].
4/13: We added [Rosenthal].
4/9: We added [Hafez].
3/31: We added [Avezum].
3/26: We added [Salehi].
3/26: We added [Oztas].
3/26: We added [Schmidt].
3/25: We added [AlQahtani].
3/23: We added [Opdam].
3/21: We added [Arabi].
3/19: We added [Ebongue].
3/10: We added [Azaña Gómez].
3/8: We added [Cortez].
3/6: We added [Khoubnasabjafari].
3/4: We added [Soto (B)].
3/3: We added [Lavilla Olleros].
3/3: We updated [Beltran Gonzalez] to the journal version.
3/1: We added [Alwafi].
2/26: We added [Rouamba].
2/22: We updated [Ader] with the new results
released 2/21/2022.
2/23: We added [Omma].
2/22: We added [Tamura (B)].
2/21: We added [Cordtz, Ugarte-Gil].
2/20: We added [Mahale].
2/16: We added [Mahto].
2/14: We added [Beaumont].
2/7: We added [Karruli].
2/6: We added [Belmont].
2/5: We added [Erden].
2/4: We added [Albanghali].
1/30: We added [Haji Aghajani].
1/24: We added [Corradini].
1/21: We added [AbdelGhaffar].
1/14: We added [Juneja].
1/13: We added [Atipornwanich]. We added identification for combined treatment,
comparison with other treatments, and use of CQ in Figure 1.
1/10/2022: We updated [Syed] to the journal version.
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 4.
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 (B)].
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 [Beltran Gonzalez].
2/25: We added [Bae].
2/20: We added [Lamback].
2/18: We added [Awad].
2/17: We added [Purwati (B)].
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.
12/28: We added [Auld, Cordtz (B)].
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.
Adjusted primary outcome results have preference over unadjusted results for a more
serious outcome when the adjustments significantly alter results.
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 (3.9.12)
with
scipy (1.8.0), pythonmeta (1.26), numpy (1.22.2), statsmodels (0.14.0), and plotly (5.6.0).
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, average treatment delay 5.0 days, 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. |
| [Atipornwanich], 10/5/2021, Randomized Controlled Trial, Thailand, South Asia, peer-reviewed, 16 authors, early treatment subset, dosage 400mg days 1-14, 800mg/day or 400mg/day, this trial compares with another treatment - results may be better when compared to placebo, this trial uses multiple treatments in the treatment arm (combined with oseltamivir/favipiravir and duranivir/ritonavir for moderate/severe, oseltamivir and duranivir/ritonavir for mild) - results of individual treatments may vary, trial NCT04303299. | risk of progression, 150.0% higher, RR 2.50, p = 1.00, treatment 1 of 60 (1.7%), control 0 of 30 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm), mild, early treatment result. |
| time to viral-, 43.3% lower, relative time 0.57, p = 0.04, treatment mean 8.9 (±6.0) n=30, control mean 15.7 (±16.7) n=30, mild, HCQ 800, primary outcome, early treatment result. | |
| time to viral-, 36.3% lower, relative time 0.64, p = 0.09, treatment mean 10.0 (±6.9) n=30, control mean 15.7 (±16.7) n=30, mild, HCQ 400, primary outcome, early treatment result. | |
| [Avezum], 3/31/2022, Double Blind Randomized Controlled Trial, Brazil, South America, peer-reviewed, 40 authors, study period 12 May, 2020 - 7 July, 2021, average treatment delay 4.0 days, dosage 400mg bid day 1, 200mg bid days 2-7, trial NCT04466540. | risk of death, 0.7% lower, RR 0.99, p = 1.00, treatment 5 of 687 (0.7%), control 5 of 682 (0.7%), NNT 18741, all-cause death. |
| risk of death, 56.0% higher, HR 1.56, p = 0.54, treatment 5 of 687 (0.7%), control 5 of 682 (0.7%), adjusted per study, univariate Firth's penalized likelihood. | |
| risk of mechanical ventilation, 32.4% higher, RR 1.32, p = 0.79, treatment 8 of 687 (1.2%), control 6 of 682 (0.9%). | |
| risk of ICU admission, 16.4% lower, RR 0.84, p = 0.61, treatment 16 of 687 (2.3%), control 19 of 682 (2.8%), NNT 219. | |
| risk of hospitalization, 23.5% lower, RR 0.77, p = 0.18, treatment 44 of 689 (6.4%), control 57 of 683 (8.3%), NNT 51. | |
| risk of hospitalization, 40.0% lower, RR 0.60, p = 0.15, treatment 267, control 265, <4 days. | |
| [Bernabeu-Wittel], 8/1/2020, retrospective, Spain, Europe, peer-reviewed, 13 authors, dosage 400mg bid day 1, 200mg bid days 2-7, this trial uses multiple treatments in the treatment arm (combined with lopinavir/ritonavir and antimicrobial treatments) - results of individual treatments may vary. | 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, average treatment delay 2.9 days, 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, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary, 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. |
| [Corradini], 4/24/2021, retrospective, Italy, Europe, peer-reviewed, 60 authors, early treatment subset, dosage not specified. | risk of death, 67.4% lower, OR 0.33, p = 0.01, treatment 641, control 102, adjusted per study, Table S6, light condition patients, multivariable, RR approximated with OR, early treatment result. |
| [Derwand], 7/3/2020, retrospective, USA, North America, peer-reviewed, 3 authors, average treatment delay 4.0 days, dosage 200mg bid days 1-5, this trial uses multiple treatments in the treatment arm (combined with AZ and zinc) - 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, average treatment delay 5.2 days, dosage 800mg day 1, 400mg days 2-7, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary. | 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, average treatment delay 4.1 days, 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, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary. | 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, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary. | 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, average treatment delay 2.5 days, dosage chloroquine 500mg bid days 1-10, this trial compares with another treatment - results may be better when compared to placebo. | 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, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary. | 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, average treatment delay 4.0 days, dosage 200mg tid days 1-10, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary. | risk of death, 83.0% lower, HR 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, HR 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, HR 0.96, p = 0.77, treatment 214 of 8,315 (2.6%), control 64 of 2,114 (3.0%), 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, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary. | 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, average treatment delay 3.8 days, dosage 400mg bid days 1-7, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary. | 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 viral clearance, 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 viral clearance, 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 viral clearance, 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 viral clearance, 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 viral clearance, 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 viral clearance, 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. | |
| [Rouamba], 2/26/2022, retrospective, Burkina Faso, Africa, peer-reviewed, mean age 42.2, 17 authors, early treatment subset, study period 9 March, 2020 - 31 October, 2020, dosage 200mg tid days 1-10, HCQ 200mg tid daily or CQ 250mg bid daily, trial NCT04445441. | risk of progression, 73.0% lower, HR 0.27, p = 0.05, treatment 23 of 399 (5.8%), control 4 of 33 (12.1%), adjusted per study, outpatients, multivariable, Cox proportional hazards, early treatment result. |
| time to viral clearance, 21.3% lower, HR 0.79, p = 0.37, treatment 399, control 33, adjusted per study, outpatients, multivariable, Cox proportional hazards, primary outcome, early treatment result. | |
| [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, primary outcome. |
| [Roy-García], 4/16/2022, Double Blind Randomized Controlled Trial, Mexico, North America, preprint, 11 authors, average treatment delay 5.0 days, dosage 200mg bid days 1-10, trial NCT04964583. | risk of progression, 100% higher, RR 2.00, p = 1.00, treatment 2 of 31 (6.5%), control 1 of 31 (3.2%), supplemental oxygen. |
| risk of progression, 233.3% higher, RR 3.33, p = 0.06, treatment 10 of 31 (32.3%), control 3 of 31 (9.7%), pneumonia. | |
| risk of progression, 225.0% higher, RR 3.25, p = 0.02, treatment 13 of 31 (41.9%), control 4 of 31 (12.9%), oxygen saturation less than 90%, dyspnea, or pneumonia. | |
| [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, OR 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, this trial uses multiple treatments in the treatment arm (combined with AZ and zinc) - results of individual treatments may vary. | 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, trial NCT04308668. | 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 viral clearance, 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, HR 0.15, p = 0.006, treatment 261, control 355, adjusted per study, binary logistic regression. |
| improvement time, 24.0% better, 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, average treatment delay 4.6 days, dosage 400mg bid day 1, 400mg qd days 2-5. | risk of hospitalization, 64.0% lower, RR 0.36, p < 0.001, treatment 25 of 175 (14.3%), control 89 of 542 (16.4%), adjusted per study, odds ratio converted to relative risk, HCQ vs. nothing, primary outcome. |
| risk of hospitalization, 50.5% lower, RR 0.49, p = 0.006, treatment 25 of 175 (14.3%), control 89 of 542 (16.4%), adjusted per study, odds ratio converted to relative risk, HCQ vs. anything else. | |
| [Yu], 8/3/2020, retrospective, China, Asia, preprint, median age 62.0, 6 authors, early treatment subset, average treatment delay 5.0 days, 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. | |
| [AbdelGhaffar], 1/11/2022, retrospective, Egypt, Africa, peer-reviewed, 17 authors, study period April 2020 - July 2020. | risk of death, 99.9% lower, RR 0.001, p < 0.001, treatment 0 of 238 (0.0%), control 900 of 3,474 (25.9%), NNT 3.9, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm). |
| [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, preprint, baseline oxygen required 95.4%, 59 authors, study period 22 March, 2020 - 29 June, 2020, average treatment delay 9.0 days, excluded in exclusion analyses: very late stage, >50% on oxygen/ventilation at baseline. | risk of death, 15.3% higher, RR 1.15, p = 0.70, treatment 11 of 150 (7.3%), control 13 of 149 (8.7%), adjusted per study, odds ratio converted to relative risk, day 90. |
| risk of death, 10.1% lower, RR 0.90, p = 0.75, treatment 15 of 150 (10.0%), control 13 of 149 (8.7%), adjusted per study, odds ratio converted to relative risk, day 28. | |
| risk of no viral clearance, 23.8% lower, RR 0.76, p = 0.68, treatment 4 of 83 (4.8%), control 5 of 81 (6.2%), NNT 74, odds ratio converted to relative risk, Table S2, day 29. | |
| [Aghajani], 4/29/2021, retrospective, Iran, Middle East, peer-reviewed, 7 authors. | risk of death, 19.5% lower, HR 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, average treatment delay 5.72 days, 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. |
| [Albanghali], 2/3/2022, retrospective, Saudi Arabia, Middle East, peer-reviewed, 8 authors, excluded in exclusion analyses: unadjusted results with no group details, substantial unadjusted confounding by indication likely. | risk of death, 34.6% higher, RR 1.35, p = 0.46, treatment 20 of 466 (4.3%), control 11 of 345 (3.2%). |
| [Albani], 8/30/2020, retrospective, Italy, Europe, peer-reviewed, 11 authors, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, substantial confounding by time 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, average treatment delay 4.0 days. | 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 at baseline. | 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 confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically. | risk of death, 52.0% higher, HR 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. |
| [AlQahtani], 3/23/2022, Randomized Controlled Trial, Bahrain, Middle East, peer-reviewed, 13 authors, study period August 2020 - March 2021, trial NCT04387760. | risk of ICU admission, 23.5% lower, RR 0.76, p = 1.00, treatment 3 of 51 (5.9%), control 4 of 52 (7.7%), NNT 55. |
| risk of no recovery, 4.1% lower, RR 0.96, p = 0.94, treatment 5 of 49 (10.2%), control 5 of 47 (10.6%), NNT 230. | |
| risk of no viral clearance, 47.4% lower, RR 0.53, p = 0.13, treatment 7 of 38 (18.4%), control 14 of 40 (35.0%), NNT 6.0. | |
| [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. |
| [Alwafi], 1/20/2022, retrospective, Saudi Arabia, Middle East, peer-reviewed, 6 authors, study period 7 March, 2020 - 15 April, 2020, excluded in exclusion analyses: excessive unadjusted differences between groups. | risk of no viral clearance, 14.7% lower, RR 0.85, p = 0.65, treatment 12 of 45 (26.7%), control 15 of 48 (31.2%), NNT 22, day 5, primary outcome. |
| risk of no viral clearance, 25.3% lower, RR 0.75, p = 0.60, treatment 7 of 45 (15.6%), control 10 of 48 (20.8%), NNT 19, day 12. | |
| [An], 7/7/2020, retrospective, South Korea, Asia, preprint, 12 authors. | time to viral clearance, 3.0% lower, HR 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 at baseline. | 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. |
| [Arabi], 7/12/2021, Randomized Controlled Trial, multiple countries, multiple regions, peer-reviewed, 1 author, trial NCT02735707. | risk of death, 44.5% higher, RR 1.44, p = 0.01, treatment 17 of 49 (34.7%), control 106 of 353 (30.0%), adjusted per study, odds ratio converted to relative risk, multivariable. |
| [Arshad], 7/1/2020, retrospective, USA, North America, peer-reviewed, 12 authors. | risk of death, 51.3% lower, HR 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. |
| [Atipornwanich], 10/5/2021, Randomized Controlled Trial, Thailand, South Asia, peer-reviewed, 16 authors, dosage 400mg days 1-14, 800mg/day or 400mg/day, this trial compares with another treatment - results may be better when compared to placebo, this trial uses multiple treatments in the treatment arm (combined with oseltamivir/favipiravir and duranivir/ritonavir for moderate/severe, oseltamivir and duranivir/ritonavir for mild) - results of individual treatments may vary, trial NCT04303299. | risk of death, 56.2% lower, RR 0.44, p = 0.07, treatment 7 of 100 (7.0%), control 16 of 100 (16.0%), NNT 11, moderate/severe, HCQ arms vs. non-HCQ arms. |
| risk of progression, 54.2% lower, RR 0.46, p = 0.02, treatment 11 of 100 (11.0%), control 24 of 100 (24.0%), NNT 7.7, moderate/severe, HCQ arms vs. non-HCQ arms. | |
| time to viral-, 7.1% lower, relative time 0.93, p = 0.51, treatment mean 10.4 (±6.3) n=50, control mean 11.2 (±5.7) n=50, moderate/severe, oseltamivir arms, primary outcome. | |
| time to viral-, 6.9% lower, relative time 0.93, p = 0.47, treatment mean 9.5 (±5.0) n=50, control mean 10.2 (±4.6) n=50, moderate/severe, favipiravir arms, primary outcome. | |
| [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 confounding by time 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. |
| [Azaña Gómez], 3/10/2022, retrospective, Spain, Europe, peer-reviewed, 10 authors, study period 1 March, 2020 - 1 October, 2020, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 35.8% lower, RR 0.64, p < 0.001, treatment 500 of 1,378 (36.3%), control 238 of 421 (56.5%), NNT 4.9. |
| [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 viral clearance, 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, average treatment delay 5.0 days, 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, average treatment delay 8.0 days, trial NCT04321616. | 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). |
| [Beaumont], 2/13/2022, retrospective, France, Europe, peer-reviewed, 22 authors, average treatment delay 6.0 days. | risk of death/intubation, 14.1% lower, HR 0.86, p = 0.55, treatment 7 of 38 (18.4%), control 88 of 258 (34.1%), NNT 6.4, adjusted per study, odds ratio converted to relative risk, Cox proportional hazards. |
| [Beltran Gonzalez], 2/23/2021, Double Blind Randomized Controlled Trial, Mexico, North America, peer-reviewed, mean age 53.8, 13 authors, average treatment delay 7.0 days, trial NCT04391127. | risk of death, 62.6% lower, RR 0.37, p = 0.27, treatment 2 of 33 (6.1%), control 6 of 37 (16.2%), 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%). | |
| [Berenguer], 8/3/2020, retrospective, Spain, Europe, peer-reviewed, 8 authors, average treatment delay 7.0 days. | 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, HR 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, average treatment delay 5.85 days, 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 viral clearance, 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, HR 1.59, p = 0.12, treatment 142, control 148, adjusted per study, all patients. |
| risk of death, 71.0% lower, HR 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 viral clearance, 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 viral clearance, 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, average treatment delay 7.0 days. | 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, average treatment delay 5.0 days. | risk of death, 32.0% lower, HR 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 required 41.8%, 14 authors, average treatment delay 7.0 days. | 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 viral clearance, 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 viral clearance, 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. |
| [Corradini], 4/24/2021, retrospective, Italy, Europe, peer-reviewed, 60 authors, dosage not specified. | risk of death, 70.2% lower, OR 0.30, p < 0.001, treatment 1,439, control 274, adjusted per study, Table S6, all patients, multivariable, RR approximated with OR. |
| risk of death, 76.8% lower, OR 0.23, p < 0.001, treatment 546, control 71, adjusted per study, Table S6, mild condition patients, multivariable, RR approximated with OR. | |
| risk of death, 84.2% lower, OR 0.16, p < 0.001, treatment 184, control 64, adjusted per study, Table S6, moderate condition patients, multivariable, RR approximated with OR. | |
| risk of death, 29.0% higher, OR 1.29, p = 0.73, treatment 68, control 37, adjusted per study, Table S6, severe condition patients, multivariable, RR approximated with OR. | |
| [Cortez], 11/11/2021, retrospective, Philippines, Asia, peer-reviewed, 29 authors, study period March 2020 - October 2020, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 15.0% lower, RR 0.85, p = 1.00, treatment 1 of 25 (4.0%), control 12 of 255 (4.7%), NNT 142. |
| [Cravedi], 7/10/2020, retrospective, USA, North America, peer-reviewed, mean age 60.0, 25 authors, average treatment delay 6.0 days, 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, HR 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, HR 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, average treatment delay 6.0 days. | 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, HR 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, average treatment delay 5.0 days, trial NCT04325893. | risk of death at day 28, 46.0% lower, RR 0.54, p = 0.21, treatment 6 of 124 (4.8%), control 11 of 123 (8.9%), 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. |
| [Ebongue], 3/18/2022, retrospective, Cameroon, Africa, peer-reviewed, 27 authors, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary. | risk of death, 43.0% lower, HR 0.57, p = 0.04, treatment 93 of 522 (17.8%), control 36 of 58 (62.1%), NNT 2.3, adjusted per study, multivariable. |
| [Falcone], 11/19/2020, prospective, propensity score matching, Italy, Europe, peer-reviewed, 19 authors, average treatment delay 6.5 days. | 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, study period 12 March, 2020 - 8 July, 2020, average treatment delay 7.0 days, 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, HR 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, HR 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 confounding by time 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, HR 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, HR 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, HR 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, HR 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, HR 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], 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, study period 21 February, 2020 - 15 May, 2020. | risk of death, 28.0% lower, HR 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, average treatment delay 8.0 days. | 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 required 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. |
| [Hafez], 4/8/2022, retrospective, United Arab Emirates, Middle East, peer-reviewed, 6 authors. | viral clearance time, 12.3% lower, HR 0.88, p = 0.59, treatment 40, control 1,446, Cox proportional hazards. |
| viral clearance time, 58.7% lower, HR 0.41, p = 0.09, treatment 4, control 1,446, HCQ + favipiravir + lopinavir/ritonavir, Cox proportional hazards. | |
| [Haji Aghajani], 4/29/2021, retrospective, Iran, Middle East, peer-reviewed, 7 authors. | risk of death, 19.5% lower, HR 0.81, p = 0.09, treatment 553, control 438, adjusted per study, Cox proportional hazards, RR approximated with OR. |
| [Hall], 2/18/2022, retrospective, USA, North America, peer-reviewed, 15 authors, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 11.2% lower, RR 0.89, p = 0.31, treatment 31 of 56 (55.4%), control 280 of 449 (62.4%), NNT 14. |
| [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, average treatment delay 7.4 days. | 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. | |
| [Hong (B)], 5/4/2022, retrospective, South Korea, Asia, peer-reviewed, 11 authors, study period 28 February, 2020 - 28 April, 2020. | recovery time, 24.9% lower, HR 0.75, p = 0.45, treatment 15, control 15, propensity score matching. |
| hospitalization time, 12.7% higher, HR 1.13, p = 0.75, treatment 15, control 15, propensity score matching. | |
| viral clearance time, 0.5% lower, HR 1.00, p = 0.99, treatment 15, control 15, propensity score matching. | |
| [Hraiech], 5/24/2020, retrospective, France, Europe, peer-reviewed, 8 authors, average treatment delay 7.0 days, 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 viral clearance, 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, average treatment delay 5.0 days. | risk of death, 1.0% lower, HR 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 confounding by time 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, average treatment delay 5.9 days, dosage 400mg bid day 1, 200mg bid days 2-10, trial NCT04354428. | 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. | |
| risk of no viral clearance, 38.3% lower, RR 0.62, p = 0.047, 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 viral clearance, 20.0% lower, RR 0.80, p = 0.49, treatment 11 of 51 (21.6%), control 12 of 52 (23.1%), adjusted per study, HCQ + AZ vs. vitamin C + folic acid. | |
| [Kalligeros], 8/5/2020, retrospective, USA, North America, peer-reviewed, 13 authors, average treatment delay 6.0 days. | risk of death, 67.0% higher, HR 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. | |
| [Karruli], 9/1/2021, retrospective, Italy, Europe, peer-reviewed, 13 authors, study period March 2020 - May 2020, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 4.8% lower, RR 0.95, p = 1.00, treatment 20 of 28 (71.4%), control 3 of 4 (75.0%), NNT 28. |
| [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, HR 0.41, p = 0.048, treatment 35 of 3,119 (1.1%), control 58 of 618 (9.4%), adjusted per study. |
| [Lamback], 2/19/2021, retrospective, Brazil, South America, peer-reviewed, 10 authors, excluded in exclusion analyses: substantial confounding by time 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, HR 0.68, p = 0.02, treatment 30 of 189 (15.9%), control 101 of 498 (20.3%), adjusted per study. |
| [Lano], 10/21/2020, retrospective, France, Europe, peer-reviewed, median age 73.5, 30 authors. | risk of death, 33.1% lower, RR 0.67, p = 0.28, treatment 56, control 66, adjusted per study, odds ratio converted to relative risk. |
| risk of 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, HR 0.27, p < 0.001, treatment 102 of 297 (34.3%), control 35 of 63 (55.6%), NNT 4.7, adjusted per study. |
| [Lavilla Olleros], 1/21/2022, retrospective, Spain, Europe, peer-reviewed, 22 authors. | risk of death, 36.2% lower, RR 0.64, p < 0.001, treatment 2,285 of 12,772 (17.9%), control 774 of 2,149 (36.0%), NNT 5.5, adjusted per study, odds ratio converted to relative risk, multivariable. |
| [Lecronier], 7/11/2020, retrospective, France, Europe, peer-reviewed, baseline oxygen required 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, HR 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 confounding by time 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, OR 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, average treatment delay 8.0 days, trial NCT04316377. | risk of death, 3.7% lower, RR 0.96, p = 1.00, treatment 1 of 27 (3.7%), control 1 of 26 (3.8%), 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, HR 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, HR 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, HR 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, HR 1.83, p = 0.009, treatment 38 of 198 (19.2%), control 37 of 395 (9.4%), adjusted per study, HCQ. | |
| [Mahale], 12/31/2020, retrospective, India, South Asia, peer-reviewed, 22 authors, study period 22 March, 2020 - 21 May, 2020, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 28.7% lower, RR 0.71, p = 0.36, treatment 25 of 102 (24.5%), control 11 of 32 (34.4%), NNT 10. |
| [Mahévas], 5/14/2020, retrospective, France, Europe, peer-reviewed, 34 authors, average treatment delay 7.0 days. | risk of death, 20.0% higher, HR 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, United Arab Emirates, Middle East, peer-reviewed, 8 authors, average treatment delay 4.0 days. | 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, average treatment delay 7.0 days. | 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, average treatment delay 7.0 days. | 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, HR 0.53, p < 0.001, treatment 575 of 2,077 (27.7%), control 231 of 743 (31.1%), adjusted per study. |
| [Modrák], 12/4/2020, retrospective, Czech Republic, Europe, preprint, 26 authors. | risk of death, 59.0% lower, RR 0.41, p = 0.04, treatment 108, control 105, Cox (single). |
| [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 confounding by time 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 confounding by time 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% better, 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. |
| [Niwas], 11/1/2020, retrospective, India, South Asia, peer-reviewed, mean age 45.5, 17 authors, excluded in exclusion analyses: excessive unadjusted differences between groups. | recovery time, 29.2% lower, relative time 0.71, p = 0.008, treatment mean 6.3 (±2.7) n=12, control mean 8.9 (±2.2) n=17. |
| risk of no viral clearance, 183.3% higher, RR 2.83, p = 0.55, treatment 2 of 12 (16.7%), control 1 of 17 (5.9%). | |
| [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%), adjusted per study, odds ratio converted to relative risk. |
| [Omma], 1/31/2022, retrospective, Turkey, Europe, peer-reviewed, 11 authors, study period 1 April, 2020 - 31 December, 2020. | risk of death, 28.2% lower, RR 0.72, p = 0.30, treatment 17 of 213 (8.0%), control 20 of 180 (11.1%), NNT 32. |
| risk of ICU admission, 50.2% lower, RR 0.50, p = 0.004, treatment 23 of 213 (10.8%), control 39 of 180 (21.7%), NNT 9.2. | |
| hospitalization time, 16.7% lower, relative time 0.83, p = 0.007, treatment 213, control 180. | |
| [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, HR 0.67, p = 0.38, treatment 397, control 59, multivariate. |
| risk of ARDS, 68.0% lower, OR 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, HR 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, HR 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, HR 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 confounding by time 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 (B)], 2/9/2021, Double Blind Randomized Controlled Trial, Indonesia, South Asia, peer-reviewed, 12 authors. | risk of no viral clearance, 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, baseline oxygen required 76.8%, 29 authors, average treatment delay 9.0 days, trial NCT04381936, 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, trial NCT04403100 (TOGETHER). | 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, HR 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 viral clearance, 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, average treatment delay 8.0 days, 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, average treatment delay 6.0 days. | 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, average treatment delay 8.0 days, excluded in exclusion analyses: substantial confounding by time 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%), 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, HR 1.35, p = 0.31, treatment 189 of 735 (25.7%), control 28 of 221 (12.7%), adjusted per study. |
| [Rosenthal], 12/10/2020, 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 at baseline. | risk of death, 8.0% higher, OR 1.08, p = 0.13, adjusted per study, multivariable, RR approximated with OR. |
| [Rouamba], 2/26/2022, retrospective, Burkina Faso, Africa, peer-reviewed, mean age 42.2, 17 authors, study period 9 March, 2020 - 31 October, 2020, dosage 200mg tid days 1-10, HCQ 200mg tid daily or CQ 250mg bid daily, trial NCT04445441. | risk of death, 80.0% lower, HR 0.20, p < 0.001, treatment 20 of 336 (6.0%), control 24 of 73 (32.9%), NNT 3.7, adjusted per study, inpatients, multivariable, Cox proportional hazards. |
| risk of progression, 20.0% lower, HR 0.80, p = 0.43, treatment 75 of 745 (10.1%), control 19 of 118 (16.1%), adjusted per study, all patients, multivariable, Cox proportional hazards. | |
| risk of progression, 7.0% higher, HR 1.07, p = 0.83, treatment 52 of 347 (15.0%), control 15 of 85 (17.6%), adjusted per study, inpatients, multivariable, Cox proportional hazards. | |
| time to viral clearance, 30.6% lower, HR 0.69, p = 0.26, treatment 746, control 118, adjusted per study, all patients, propensity score matching, multivariable, Cox proportional hazards, primary outcome. | |
| time to viral clearance, 13.0% lower, HR 0.87, p = 0.29, treatment 746, control 118, adjusted per study, all patients, without PSM, multivariable, Cox proportional hazards, primary outcome. | |
| time to viral clearance, 13.8% lower, HR 0.86, p = 0.37, treatment 345, control 86, adjusted per study, inpatients, multivariable, Cox proportional hazards, primary outcome. | |
| [Réa-Neto], 4/27/2021, Randomized Controlled Trial, Brazil, South America, peer-reviewed, 6 authors, average treatment delay 8.0 days, trial NCT04420247. | risk of death, 57.0% higher, RR 1.57, p = 0.20, treatment 16 of 53 (30.2%), control 10 of 52 (19.2%). |
| risk of mechanical ventilation, 115.0% higher, RR 2.15, p = 0.03, treatment 53, control 52. | |
| 9-point scale clinical status, 147.0% higher, OR 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, average treatment delay 7.2 days, 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. |
| [Salehi], 3/11/2022, retrospective, Iran, Middle East, preprint, mean age 62.0, 11 authors, study period April 2021 - September 2021, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 14.5% higher, RR 1.14, p = 0.44, treatment 53 of 86 (61.6%), control 21 of 39 (53.8%). |
| [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 confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically. | risk of death, 240.0% higher, OR 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, average treatment delay 7.0 days, 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, study period 1 October, 2020 - 10 March, 2021, this trial compares with another treatment - results may be better when compared to placebo, trial NCT04779047, 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%), 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. | |
| [Schmidt], 11/12/2021, retrospective, USA, North America, peer-reviewed, 42 authors, study period 17 March, 2020 - 11 February, 2021, excluded in exclusion analyses: confounding by indication is likely and adjustments do not consider COVID-19 severity at baseline. | risk of death, 333.0% higher, OR 4.33, p < 0.001, treatment 70, control 407, adjusted per study, propensity score matching, multivariable, RR approximated with OR. |
| risk of severe case, 613.0% higher, OR 7.13, p < 0.001, treatment 70, control 407, adjusted per study, propensity score matching, multivariable, RR approximated with OR. | |
| [Schwartz], 6/18/2021, Double Blind Randomized Controlled Trial, Canada, North America, peer-reviewed, 20 authors, average treatment delay 7.0 days, 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, average treatment delay 5.0 days. | 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 at baseline. | 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, average treatment delay 8.0 days, trial NCT04322396. | risk of death, 92.0% lower, RR 0.08, p = 0.32, treatment 1 of 61 (1.6%), control 2 of 56 (3.6%), 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, HR 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 required 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 required 100.0%, 6 authors, average treatment delay 9.0 days, 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], 3/2/2022, retrospective, Peru, South America, peer-reviewed, median age 58.0, 10 authors, study period April 2020 - August 2020, dosage not specified, excluded in exclusion analyses: unadjusted results with no group details, substantial unadjusted confounding by indication likely, substantial confounding by time possible due to significant changes in SOC and treatment propensity near the start of the pandemic. | risk of death, 6.0% higher, HR 1.06, p = 0.46, treatment 292 of 590 (49.5%), control 362 of 828 (43.7%), Cox proportional hazards. |
| [Soto-Becerra], 10/8/2020, retrospective, database analysis, Peru, South America, preprint, median age 59.4, 4 authors, study period 1 April, 2020 - 19 July, 2020, 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, HR 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, HR 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 confounding by time 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 confounding by time 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 confounding by time 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 confounding by time 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 confounding by time 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 confounding by time 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 confounding by time 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%), 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, average treatment delay 5.0 days. | 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, average treatment delay 6.0 days. | risk of no hospital discharge, 38.7% lower, OR 0.61, p = 0.02, treatment 674, control 252, multivariate, RR approximated with OR. |
| [Tamura], 7/13/2021, retrospective, Brazil, South America, peer-reviewed, 4 authors, study period 10 March, 2020 - 13 November, 2020, excluded in exclusion analyses: substantial unadjusted confounding by indication likely, substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically. | risk of death, 299.0% higher, OR 3.99, p = 0.04, treatment 25, control 163, adjusted per study, multivariable, 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, average treatment delay 16.6 days. | 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 confounding by time 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, OR 1.03, p = 0.87, treatment 241, control 236, day 28, RR approximated with OR. | |
| risk of 7-point scale, 2.0% lower, OR 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, average treatment delay 9.0 days. | 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. |
| [Tsanovska], 3/3/2022, prospective, Bulgaria, Europe, peer-reviewed, 8 authors, study period 6 November, 2020 - 28 December, 2020. | risk of death, 57.9% lower, RR 0.42, p = 0.03, treatment 8 of 70 (11.4%), control 19 of 70 (27.1%), NNT 6.4, propensity score matching. |
| risk of mechanical ventilation, 73.9% lower, RR 0.26, p < 0.001, treatment 6 of 70 (8.6%), control 23 of 70 (32.9%), NNT 4.1, propensity score matching. | |
| risk of ICU admission, 70.4% lower, RR 0.30, p < 0.001, treatment 8 of 70 (11.4%), control 27 of 70 (38.6%), NNT 3.7, propensity score matching. | |
| [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 required 63.3%, mean age 66.2, 18 authors, average treatment delay 7.0 days, 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%). |
| [Uyaroğlu], 3/17/2022, retrospective, propensity score matching, Turkey, Europe, peer-reviewed, 6 authors, study period 20 March, 2020 - 30 September, 2020, this trial compares with another treatment - results may be better when compared to placebo. | risk of death, 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 ICU admission, 66.7% lower, RR 0.33, p = 1.00, treatment 0 of 42 (0.0%), control 1 of 42 (2.4%), NNT 42, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm). | |
| hospitalization time, 9.8% lower, relative time 0.90, p = 0.90, treatment 42, control 42. | |
| [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 confounding by time 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 (C)], 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 at baseline. | 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 viral clearance, 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, average treatment delay 1.0 days, 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 = 0.049, 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 confounding by time 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, average treatment delay 7.0 days. | 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, OR 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, OR 1.08, p = 0.64, HCQ vs. other cDMARDs, RR approximated with OR. |
| risk of hospitalization, 18.0% lower, OR 0.82, p = 0.03, HCQ vs. other cDMARDs, RR approximated with OR. | |
| risk of death, 19.0% higher, OR 1.19, p = 0.32, HCQ vs. MTX, RR approximated with OR. | |
| risk of hospitalization, 12.0% lower, OR 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, 58.7% 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%), 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%), 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. | |
| [Belmont], 10/6/2021, prospective, USA, North America, preprint, 1 author, trial NCT04354870. | risk of symptomatic case, 78.6% lower, RR 0.21, p = 0.21, treatment 1 of 56 (1.8%), control 2 of 24 (8.3%), NNT 15. |
| risk of case, 14.3% lower, RR 0.86, p = 1.00, treatment 4 of 56 (7.1%), control 2 of 24 (8.3%), NNT 84. | |
| [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], 8/27/2021, retrospective, population-based cohort, Denmark, Europe, peer-reviewed, 8 authors, study period 1 March, 2020 - 2 February, 2021. | risk of hospitalization, 40.0% lower, HR 0.60, p = 0.39, treatment 1,170, control 1,363, adjusted per study. |
| [Cordtz (B)], 12/28/2020, retrospective, population-based cohort, Denmark, Europe, peer-reviewed, 10 authors. | risk of hospitalization, 24.0% lower, HR 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, HR 0.45, p = 0.28, treatment 3 of 2,722 (0.1%), control 38 of 26,718 (0.1%), 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. | |
| [Del Amo], 3/4/2022, Double Blind Randomized Controlled Trial, placebo-controlled, multiple countries, multiple regions, preprint, 1 author, study period April 2020 - May 2021, dosage 200mg daily, trial NCT04334928. | risk of symptomatic case, 51.0% lower, RR 0.49, p = 0.79, treatment 3 of 231 (1.3%), control 5 of 223 (2.2%), NNT 106, HCQ, Kaplan–Meier. |
| risk of symptomatic case, 61.0% lower, RR 0.39, p = 0.72, treatment 3 of 220 (1.4%), control 5 of 223 (2.2%), TDF+HCQ, Kaplan–Meier. | |
| risk of case, 27.0% lower, RR 0.73, p = 0.31, treatment 21 of 231 (9.1%), control 23 of 223 (10.3%), HCQ, Kaplan–Meier. | |
| risk of case, 49.0% lower, RR 0.51, p = 0.09, treatment 13 of 220 (5.9%), control 23 of 223 (10.3%), NNT 23, TDF+HCQ, Kaplan–Meier. | |
| [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. |
| [Erden], 1/23/2022, retrospective, Turkey, Europe, peer-reviewed, 11 authors, excluded in exclusion analyses: unadjusted results with no group details. | risk of death, 150.0% higher, RR 2.50, p = 1.00, treatment 1 of 6 (16.7%), control 0 of 3 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm). |
| risk of hospitalization, 75.0% lower, RR 0.25, p = 0.23, treatment 1 of 6 (16.7%), control 2 of 3 (66.7%), NNT 2.0. | |
| [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, 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, peer-reviewed, 6 authors, excluded in exclusion analyses: not fully adjusting for the different baseline risk of systemic autoimmune patients. | risk of death, 13.0% lower, HR 0.87, p = 0.15, vs. past use (better match for systemic autoimmune diseases). |
| risk of hospitalization, 3.0% lower, HR 0.97, p = 0.63, vs. past use (better match for systemic autoimmune diseases). | |
| risk of case, 9.0% lower, HR 0.91, p = 0.02, vs. past use (better match for systemic autoimmune diseases). | |
| risk of death, 8.0% higher, HR 1.08, p = 0.26, vs. never used. | |
| risk of hospitalization, 6.0% higher, HR 1.06, p = 0.13, vs. never used. | |
| risk of case, 5.0% lower, HR 0.95, p = 0.03, 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%), adjusted per study, multivariate. | |
| [Juneja], 1/7/2022, retrospective, India, South Asia, peer-reviewed, 9 authors, study period 2 April, 2020 - 3 September, 2020, excluded in exclusion analyses: excessive unadjusted differences between groups. | risk of severe case, 141.8% higher, RR 2.42, p = 0.59, treatment 2 of 996 (0.2%), control 1 of 1,204 (0.1%). |
| risk of case, 6.4% higher, RR 1.06, p = 0.67, treatment 103 of 996 (10.3%), control 117 of 1,204 (9.7%). | |
| [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, peer-reviewed, mean age 31.2, 16 authors, study period 23 April, 2020 - 11 June, 2020. | risk of case, 62.3% lower, RR 0.38, p = 0.01, treatment 10 of 258 (3.9%), control 15 of 100 (15.0%), NNT 9.0, 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, OR 1.44, p = 0.25, treatment 5,488, control 54,846, RR approximated with OR. |
| risk of case, 10.0% lower, HR 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. | |
| [Khoubnasabjafari], 1/13/2021, retrospective, Iran, Middle East, peer-reviewed, 10 authors. | risk of case, 16.7% lower, RR 0.83, p = 0.59, treatment 34 of 1,436 (2.4%), control 12 of 422 (2.8%), NNT 210. |
| [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%). |
| [MacFadden], 3/29/2022, retrospective, Canada, North America, peer-reviewed, 9 authors, study period 15 January, 2020 - 31 December, 2020. | risk of case, 12.0% lower, OR 0.88, p = 0.01, RR approximated with OR. |
| [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%). | |
| [Mahto], 2/15/2021, retrospective, India, South Asia, peer-reviewed, 6 authors, excluded in exclusion analyses: unadjusted results with no group details. | risk of IgG positive, 26.9% lower, RR 0.73, p = 0.38, treatment 9 of 89 (10.1%), control 84 of 600 (14.0%), NNT 26, unadjusted, odds ratio converted to relative risk. |
| [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, trial NCT04341441. | 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, trial NCT04334148. | 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. | |
| [Opdam], 2/23/2022, retrospective, Netherlands, Europe, peer-reviewed, 9 authors. | risk of hospitalization, 45.0% lower, OR 0.55, p = 0.18, treatment 8 of 81 (9.9%) cases, 59 of 396 (14.9%) controls, NNT 17, case control OR. |
| [Oztas], 3/21/2022, retrospective, Turkey, Europe, peer-reviewed, 15 authors, excluded in exclusion analyses: not adjusting for the different baseline risk of systemic autoimmune patients, excessive unadjusted differences between groups. | risk of hospitalization, 215.1% higher, RR 3.15, p = 0.36, treatment 3 of 317 (0.9%), control 1 of 333 (0.3%). |
| risk of symptomatic case, 40.1% higher, RR 1.40, p = 0.44, treatment 16 of 317 (5.0%), control 12 of 333 (3.6%). | |
| risk of case, 5.0% higher, RR 1.05, p = 0.88, treatment 22 of 317 (6.9%), control 22 of 333 (6.6%). | |
| [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, trial NCT04328467. | 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, HR 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, HR 1.03, p = 0.83, treatment 70 of 30,569 (0.2%), control 477 of 164,068 (0.3%), 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, trial NCT04318015. | 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, OR 0.94, p = 0.75, RR approximated with OR. |
| [Samajdar], 11/17/2021, retrospective, India, South Asia, peer-reviewed, 9 authors, study period 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, peer-reviewed, 8 authors, trial NCT04359537. | risk of symptomatic case, 59.7% higher, RR 1.60, p = 0.41, treatment 10 of 48 (20.8%), control 6 of 46 (13.0%), group 1. |
| risk of symptomatic case, 110.5% higher, RR 2.10, p = 0.13, treatment 14 of 51 (27.5%), control 6 of 46 (13.0%), group 2. | |
| risk of symptomatic case, 16.4% lower, RR 0.84, p = 0.77, treatment 6 of 55 (10.9%), control 6 of 46 (13.0%), NNT 47, group 3. | |
| risk of case, 91.7% higher, RR 1.92, p = 0.12, treatment 15 of 38 (39.5%), control 7 of 34 (20.6%), group 1. | |
| risk of case, 136.6% higher, RR 2.37, p = 0.02, treatment 19 of 39 (48.7%), control 7 of 34 (20.6%), group 2. | |
| risk of case, 21.4% higher, RR 1.21, p = 0.77, treatment 8 of 32 (25.0%), control 7 of 34 (20.6%), 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%), 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. | |
| [Ugarte-Gil], 2/16/2022, retrospective, multiple countries, multiple regions, peer-reviewed, 58 authors. | risk of severe case, 44.4% lower, OR 0.56, p = 0.007, treatment 665, control 230, adjusted per study, HCQ/CQ only vs. no SLE medication, multivariable, RR approximated with OR. |
| [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 (B)], 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 = 0.049, treatment 17 of 178 (9.6%), control 27 of 221 (12.2%), 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, trial NCT04328961. | risk of hospitalization, 3.7% higher, RR 1.04, p = 1.00, treatment 1 of 407 (0.2%), control 1 of 422 (0.2%). |
| risk of case, 27.0% higher, HR 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, HR 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, HR 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, HR 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, HR 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, this trial compares with another treatment - results may be better when compared to placebo. | 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, trial NCT04408456. | 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, 45.6% lower, RR 0.54, p = 0.39, treatment 4 of 1,196 (0.3%), control 8 of 1,301 (0.6%), NNT 357, per supplemental appendix table S7, excluding patient that did not take any study medication and had an unknown cause of death. |
| risk of hospitalization, 16.8% lower, RR 0.83, p = 0.71, treatment 13 of 1,196 (1.1%), control 17 of 1,301 (1.3%), NNT 455, per supplemental appendix table S7, excluding patient that did not take any study medication and had an unknown cause of death. | |
| 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, trial NCT04446104. | risk of symptomatic case, 35.1% lower, RR 0.65, p = 0.047, 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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Please send us corrections, updates, or comments. Vaccines and
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the risk of endemic status. We do not provide medical advice. Before taking
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