Hydroxychloroquine for treatment of non‐severe COVID‐19 patients; systematic review and meta‐analysis of controlled clinical trials

Elsawah, Hozaifa Khalil; Elsokary, Mohamed Ahmed; Elrazzaz, Mahmoud Gamal; ElShafey, Ahmed Hane

BACKGROUND: Being a pandemic and having a high global case fatality rate directed us to assess the evidence strength of hydroxychloroquine efficacy in treating COVID‐19 arising from clinical trials and to update the practice with the most reliable clinical evidence. METHODS: A comprehensive search was started in June up to July‐18, 2020 in many databases, including PubMed, Embase and others. Of 432 studies found, only six studies fulfilled the inclusion criteria which includes: clinical trials, age>12 years with non‐severe COVID‐19, PCR‐confirmed COVID‐19, hydroxychloroquine is the intervention beyond the usual care. Data extraction and bias risk assessment were done by two independent authors. Both fixed‐effect and random‐effect models were utilized for pooling data using risk difference as a summary measure. The primary outcomes are clinical and radiological COVID‐19 progression, SARS‐CoV‐2 clearance in the pharyngeal swab, and mortality. The secondary outcomes are the adverse effects of hydroxychloroquine. RESULTS: Among 609 COVID‐19 confirmed patients obtained from pooling 6 studies, 294 patients received Hydroxychloroquine and 315 patients served as a control. Hydroxychloroquine significantly prevent early radiological progression relative to control with risk difference and 95% confidence interval of ‐0.2 (‐0.36 to ‐0.03). On the other hand, hydroxychloroquine did not prevent clinical COVID‐19 progression, reduce 5‐days mortality, or enhance viral clearance on days 5, 6, 7. Moreover, many adverse effects were reported with hydroxychloroquine therapy. CONCLUSIONS: Failure of hydroxychloroquine to show viral clearance or clinical benefits with additional adverse effects outweigh its protective effect from radiological progression in non‐severe COVID‐19 patients. Benefit‐risk balance should guide hydroxychloroquine use in COVID‐19. This article is protected by copyright. All rights reserved.