CAUTION: The evidence available regarding COVID-19 treatments (even limited to the randomized trial evidence) is very limited and potentially unstable. Much of the available evidence is not published in peer-reviewed final form, and most treatments are currently considered experimental.
| Outcome | Sample size (# trials, # participants, # events) | Result without hydroxychloroquine | Result with hydroxychloroquine | Effect estimate (hydroxychloroquine effect) | Certainty of finding (Quality of evidence) | What this means |
|---|---|---|---|---|---|---|
| Mortality | 1 trial, 4674 participants | 235 out of 1,000 (23.5%) | 257 out of 1,000 (25.7%) | Risk difference 2.2%; Hazard ratio 1.11 (95% CI 0.98 to 1.26, p = 0.1) 22 more out of 1,000 (95% CI 4 fewer to 51 more) | Moderate certainty due to risk of bias | Hydroxychloroquine does not appear to reduce mortality in patients hospitalized with COVID-19 |
| Severe or critical illness within 14 days | 2 trials, 92 participants, 5 events | 87 out of 1,000 (8.7%) | 54 out of 1,000 (5.4%) 95% CI 0 to 246 out of 1,000 (0% to 24.6%) | Risk difference -3.3% (95% CI -22.4% to +15.9%) 33 fewer out of 1,000 (95% CI 224 fewer to 159 more) | Very low certainty due to risk of bias, inconsistency and imprecision | Insufficient evidence to determine if hydroxychloroquine has an effect on likelihood of progression to severe or critical illness within 14 days in COVID-19 pneumonia with mild respiratory illness |
| Progression to severe or critical illness within 28 days | 1 trial, 150 participants, 1 event | 0 events occurred | 13 out of 1,000 (1.3%) 95% CI 0 to 72 out of 1,000 (0% to 7.2%) | Risk difference 1.3% (95% CI -3.7% to 7.2%) 13 more out of 1,000 (95% CI 37 fewer to 72 more) | Very low certainty due to risk of bias, indirectness and very serious imprecision | Insufficient evidence to determine if hydroxychloroquine has an effect on progression to severe or critical illness within 28 days |
| Symptom relief by 28 days | 1 trial, 119 participants | 666 out of 1,000 (66.6%) | 600 out of 1,000 (60%) 95% CI 253 to 946 out of 1,000 (25.3% to 94.6%) | Risk difference (Kaplan-Meier estimate) -6.6% (95% CI -41.3% to +28.0%) 66 fewer out of 1,000 (95% CI 413 fewer to 280 more) | Very low certainty due to very serious risk of bias, indirectness and very serious imprecision (and possible invalidation by incorrect data reporting) | Insufficient evidence to determine if hydroxychloroquine has an effect on symptom relief by 28 days |
| Time to symptom relief | 1 trial, 119 participants | Median 21 days | Median 19 days | Median difference -2 days Hazard ratio 1.01 (95% CI 0.59 to 1.74) | Very low certainty due to very serious risk of bias, indirectness and imprecision | Insufficient evidence to determine if hydroxychloroquine has an effect on time to symptom relief |
| Time to cough remission | 1 trial, 37 participants | Mean 3.1 days (SD 1.5 days) | Mean 2.0 days (SD 0.2 days) | Mean difference -1.1 days (95% CI -1.8 days to -0.4 days, p = 0.0016) | Very low certainty due to risk of bias, inconsistency and imprecision | Hydroxychloroquine might reduce time to cough remission, but this finding not repeated in a second trial |
| Time to fever remission | 2 trials, 1290 participants, 108 events | Mean difference -1 day in 1 trial, Median difference 0 days in 1 trial | Very low certainty due to risk of bias, inconsistency and imprecision | Insufficient evidence to determine if hydroxychloroquine has an effect on time to fever remission in COVID-19 pneumonia with mild respiratory illness | ||
| Adverse events (any) - 400 mg/day x 5 days | 2 trials, 92 participants, 9 events | 65 out of 1,000 (6.5%) | 130 out of 1,000 (13%) 95% CI 16 to 245 out of 1,000 (1.6% to 24.5%) | Risk difference +6.5% (95% CI -4.9% to 18.0%) 65 more out of 1,000 (95% CI 49 fewer to 180 more) | Very low certainty due to risk of bias and very serious imprecision | Insufficient evidence to determine if hydroxychloroquine 400 mg/day has an effect on likelihood of any adverse events in COVID-19 pneumonia with mild respiratory illness |
| Diarrhea - 400 mg/day x 5 days | 2 trials, 92 participants, 2 events | 0 out of 1,000 (0%) | 44 out of 1,000 (4.4%) 95% CI 0 to 124 out of 1,000 (0% to 12.4%) | Risk difference +4.4% (95% CI -3.7% to +12.4%) 44 more out of 1,000 (95% CI 37 fewer to 124 more) | Very low certainty due to risk of bias and very serious imprecision | Insufficient evidence to determine if hydroxychloroquine 400 mg/day has an effect on likelihood of diarrhea in COVID-19 pneumonia with mild respiratory illness |
| Chen Z 2020 | Chen J 2020 | Tang W 2020 | RECOVERY 2020 | |
|---|---|---|---|---|
| Population | ||||
| Characteristics | Adults with COVID-19 pneumonia and mild illness admitted to hospital | Adults with COVID-19 pneumonia and mild illness admitted to hospital | Adults with COVID-19 and mild illness | COVID-19 (suspected or confirmed) and hospitalized - any age |
| Observed cohort | 62 patients admitted to Renmin Hospital of Wuhan University February 4-28, 2020 | 30 patients treated at Shanghai Public Health Clinical Center February 6-25, 2020 | 150 patients treated at 16 centers in China February 11-29, 2020 | 4,674 patients in United Kingdom (175 NHS hospitals) March 19, 2020 to June 4, 2020 |
| Dose | Oral hydroxychloroquine sulfate 200 mg twice daily for 5 days | Oral hydroxychloroquine sulfate 400 mg once daily for 5 days | Oral hydroxychloroquine 1,200 mg daily for 3 days then 800 mg daily for total treatment duration 2 weeks for mild/moderate illness (3 weeks for severe illness) | Hydroxychloroquine 800 mg twice 6 hours apart then 6 hours later 400 mg twice daily for 10 days |
| Risk of Bias | Moderate risk of bias | Moderate risk of bias | High risk of bias | Moderate risk of bias |
| Outcomes | ||||
| Mortality | 0/15 vs. 0/15 No deaths occurred | 0/75 vs. 0/75 No deaths occurred | 28-day mortality 25.7% hydroxychloroquine vs. 23.5% control (total n = 4,674) Risk difference 2.2%; Hazard ratio 1.11 (95% CI 0.98 to 1.26) | |
| Severe or critical illness within 14 days | Progression to severe illness within 5 days in 0/31 vs. 4/31 Risk difference -12.9% (95% CI -28.9% to +0.6%) | Critical illness in 1/15 vs. 0/15 Risk difference +6.7% (95% CI -14.4% to +29.8%) | ||
| Progression to severe or critical illness within 28 days | 1/75 vs. 0/75 Risk difference 1.3% (95% CI -3.7% to +7.2%) | |||
| Symptom relief by 28 days | ||||
| Time to symptom relief | Median 19 days vs. 21 days, based on 119 patients with symptoms Median difference -2 days, Hazard ratio 1.01 (95% CI 0.59 to 1.74) | |||
| Time to cough remission | Mean 2.0 days (SD 0.2 days, n=22) vs. 3.1 days (SD 1.5 days, n=15) Mean difference -1.1 days (95% CI -1.8 days to -0.4 days) | |||
| Time to fever remission | Mean 2.2 days (SD 0.4 days, n=22) vs. 3.2 days (SD 1.3 days, n=17) Mean difference -1 day (95% CI -1.6 days to -0.4 days) | Median 1 day (range 0 to 2 days) vs. 1 day (range 0 to 3 days) Median difference 0 days (range -3 days to +2 days) | ||
| Adverse events (any) | 2/31 vs. 0/31 Risk difference +6.5% (95% CI -5.5% to +20.7%) | 4/15 vs. 3/15 Risk difference +6.7% (95% CI -23% to +35.1%) | 21/70 vs. 7/80 Risk difference 21.3% (95% CI 8.7% to 33.6%) | |
| Diarrhea | 0/31 vs. 0/31 No events occurred | 2/15 vs. 0/15 Risk difference +13.3% (95% CI -9.2% to +37.9%) | 7/70 vs. 0/80 Risk difference 10% (95% CI 3.2% to 19.2%) |