Safety of hydroxychloroquine in COVID-19 and other diseases: a systematic review and meta-analysis of 53 randomized trials

Abstract

Introduction Many concerns still exist regarding the safety of hydroxychloroquine (HCQ) in the treatment of Coronavirus Disease 2019 (COVID-19). Objectives The purpose of this study was to evaluate the safety of HCQ in the treatment of COVID-19 and other diseases by performing a systematic review and meta-analysis. Methods Randomized controlled trials (RCTs) reporting the safety of HCQ in PubMed, Embase, and Cochrane Library were retrieved starting from the establishment of the database till June 5, 2020. Literature screening, data extraction, and assessment of risk bias were performed independently by two reviewers. Results We identified 53 eligible studies involving 5496 patients. The meta-analysis indicated that the risk of adverse effects (AEs) in the HCQ group was significantly increased compared with that in the control group (RD 0.05, 95%CI, 0.02 to 0.07, P = 0.0002), and the difference was also statistically significant in the COVID-19 subgroup (RD 0.15, 95%CI, 0.07 to 0.23, P = 0.0002) as well as in the subgroup for other diseases (RD 0.03, 95%CI, 0.01 to 0.04, P = 0.003). Conclusions HCQ is associated with a high total risk of AEs compared with the placebo or no intervention in the overall population. Given the small number of COVID-19 participants included, we should be cautious regarding the conclusion stating that HCQ is linked with an increase incidence of AEs in patients with COVID-19, which we hope to confirm in the future through well-designed and larger sample size studies. Electronic supplementary material The online version of this article (10.1007/s00228-020-02962-5) contains supplementary material, which is available to authorized users.

Safety of hydroxychloroquine for treatment or prevention of SARS‐CoV‐2 infection: A rapid systematic review and meta‐analysis of randomized clinical trials

“…Results are coherent with a previous evidence synthesis collecting data only from RCTs, but not limited to COVID‐19, being focused on other settings such as rheumatological diseases characterized by different HCQ schedules and including fewer studies in the framework of treatment or prevention of SARS‐CoV‐2 infection 12 …”

Worsening of heart failure by coronavirus disease 2019 is associated with high mortality

“…Many concerns exist regarding the safety of hydroxychloroquine in the treatment of COVID-19. 4 Treatment for HF individuals with COVID-19 included best practices for supportive management of acute hypoxic respiratory failure, haemodynamics, organ failures, and general clinical status. Eight patients progressed to SARS requiring invasive pulmonary mechanical ventilation, seven needed non-invasive pulmonary ventilation, and one patient received supplemental oxygen by catheter.…”

“…hydroxychloroquine, chloroquine, clarithromycin, azithromycin, antiviral therapy, convalescent plasma, and immunomodulatory agents). Many concerns exist regarding the safety of hydroxychloroquine in the treatment of COVID‐19 4 . Treatment for HF individuals with COVID‐19 included best practices for supportive management of acute hypoxic respiratory failure, haemodynamics, organ failures, and general clinical status.…”

Renal Manifestations of Covid-19: Physiology and Pathophysiology

“…However, a recent study at a large medical center in New York City that examined the association between hydroxychloroquine use and intubation or death of patients with Covid-19, revealed that hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end-point of intubation or death [ 99 ]. However, most recent meta-analysis studies demonstrated that hydroxychloroquine administration might cause harm in COVID-19 patients [ 100 , 101 ].…”