Hydroxychloroquine in COVID-19: an updated systematic review and meta-analysis

BackgroundHydroxychloroquine is being administered among patients with COVID-19 infection in many healthcare systems across the world, considering its in vitro effect against the SARS-CoV-2 virus. In spite of several observational studies and a few randomized controlled trials, the effect of hydroxychloroquine on patients with COVID-19 infection remains unclear. We undertook this systematic review with meta-analysis to evaluate the efficacy and safety of hydroxychloroquine among patients with COVID-19 infection. MethodsWe searched PubMed, Embase, the Cochrane Library, Web of Science, medRxiv, and other relevant resources until August 1, 2020. We included randomized controlled trials and observational studies in which hydroxychloroquine was administered and compared to a control group. Data were extracted, and quality assessment of the studies was carried out. We evaluated symptomatic progression, mortality, viral clearance, evolution of changes on chest CT imaging, and adverse events. A fixed or random-effects model was used depending on outcome heterogeneity. ResultsWe included 23 studies, including seven randomized controlled trials and 16 observational studies. Among these, 11,029 patients received hydroxychloroquine alone or in combination, while 12063 did not. Mortality was reported at different points in time. The overall mortality was not significantly different among patients who received hydroxychloroquine compared to the control group (OR: 0.94, 95% CI: 0.72-1.22; p = 0.63). Clinical worsening did not differ between patients who received hydroxychloroquine compared to those who did not (OR 0.93, 95% CI: 0.57-1.52; p = 0.77). Negative conversion, assessed by RT-PCR, did not differ significantly between the hydroxychloroquine and the control groups (OR: 0.67, CI: 0.21-2.11; p = 0.49). The evolution of changes on chest CT imaging was reported only in two studies; a more pronounced improvement was observed with the use of hydroxychloroquine compared to standard care (OR: 2.68, CI: 1.1-6.55; P = 0.03). The incidence of adverse events was significantly higher with hydroxychloroquine (OR: 5.95, CI: 2.56-13.83; p < 0.00001). ConclusionsOur meta-analysis does not suggest improvement in mortality, clinical progression, or negative conversion by RT-PCR among patients with COVID-19 infection who are treated with hydroxychloroquine. There was a significantly higher incidence of adverse events with hydroxychloroquine use.