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The efficacy and safety of hydroxychloroquine for COVID-19 prophylaxis and clinical assessment: an updated meta-analysis of randomized trials

Han et al., Journal of Thoracic Disease, doi:10.21037/jtd-23-1043
May 2024  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
*, now with p < 0.00000000001 from 411 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,300+ studies for 75 treatments.
Meta analysis of 9 RCTs with 7,825 participants showing significantly lower COVID-19 cases with HCQ prophylaxis. Authors only cover the period until January 2022. The very long publication delay may be due to the reported difficulty publishing positive results. Additional more recent studies further confirm efficacy. Adverse events were increased, however authors do not distinguish serious and minor adverse events. The primary contributor to the increased adverse events is Mitjà et al. which reported very high gastrointestinal side effects with treatment, which is not seen in other major trials. Mitjà et al. do not specify whether HCQ was administered with food, which is known to reduce gastrointestinal side effects.
8 meta analyses show significant improvements with hydroxychloroquine for mortality2-5, hospitalization2, recovery6, combined death/hospitalization/cases7, and cases8,9.
Currently there are 39 HCQ for COVID-19 early treatment studies, showing 76% lower mortality [61‑85%], 67% lower ventilation [-710‑99%], 31% lower ICU admission [1‑53%], and 41% lower hospitalization [28‑51%].
Han et al., 31 May 2024, peer-reviewed, 3 authors. Contact:
This PaperHCQAll
The efficacy and safety of hydroxychloroquine for COVID-19 prophylaxis and clinical assessment: an updated meta-analysis of randomized trials
Xudong Han, Wei Shi, MS. Ya Yang
Journal of Thoracic Disease, doi:10.21037/jtd-23-1043
Background: Coronavirus disease 2019 (COVID-19), a disease that affected tens of millions of people, upended the lives of countless individuals around the globe. The chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) were the most frequently cited as potential treatments and preventatives against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary aim of this investigation was to scrutinize the effectiveness and safety of HCQ for COVID-19 prevention and to present powerful evidence and reference for clinical practice. Methods: PubMed, Ovid and the Cochrane COVID-19 Register of Controlled Trials (CENTRAL) were systematically searched from inception to January 31, 2022. Randomized controlled trials (RCTs) trials that included participants who were SARS-CoV-2 negative at the time of registration were enrolled in this metaanalysis. The intervention group took HCQ or CQ orally. The control group was not blinded by quinine or placebo. Pooled relative risk (RR) of SARS-CoV-2 infection, mortality, hospitalization, adverse events, and compliance were calculated. The software tools utilized for statistical analyses were Stata 14 and Review Manager 5.3. Results: A total of 9 studies including 7,825 participants were enrolled. Bias of individual studies were assessed as low risk. The pooled RR for SARS-CoV-2 infection was 0.75 [95% confidence interval (CI): 0.68-0.83] (z=-4.01, P<0.0001; I 2 =11%). The pooled RR for hospitalization was 0.72 (95% CI: 0.35-1.50) (z=0.87, P=0.39; I 2 =0.0%). The pooled RR for mortality and adverse events were 3.26 (95% CI: 0.13-79.74) (z=0.72, P=0.47; I 2 =0.0%) and 1.90 (95% CI: 1.20-3.02) (z=2.73, P=0.0063; I 2 =94%). Conclusions: Results of this meta-analysis indicated significant impact of HCQ on SARS-CoV-2 infection with higher risk of adverse events. These findings must be considered with caution, and further research is necessary to delineate the specific circumstances where HCQ may be effective for COVID-19 prevention.
Conflicts of Interest
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