Efficacy of chloroquine and hydroxychloroquine in treating COVID-19 infection: A meta-review of systematic reviews and an updated meta-analysis

Travel Med Infect Dis. 2021 Sep-Oct;43:102135. doi: 10.1016/j.tmaid.2021.102135. Epub 2021 Jul 12.


Objective: To synthesize findings from systematic reviews and meta-analyses on the efficacy and safety of chloroquine (CQ) and hydroxychloroquine (HCQ) with or without Azithromycin for treating COVID-19, and to update the evidence using a meta-analysis.

Methods: A comprehensive search was carried out in electronic databases for systematic reviews, meta-analyses and experimental studies which investigated the efficacy and safety of CQ, HCQ with or without Azithromycin to treat COVID-19. Findings from the reviews were synthesised using tables and forest plots and the quality effect model was used for the updated meta-analysis. The main outcomes were mortality, the need for intensive care services, disease exacerbation, viral clearance and occurrence of adverse events.

Results: Thirteen reviews with 40 primary studies were included. Two meta-analyses reported a high risk of mortality, with ORs of 2.2 and 3.0, and the two others found no association between HCQ and mortality. Findings from two meta-analyses showed that HCQ with Azithromycin increased the risk of mortality, with similar ORs of 2.5. The updated meta-analysis of experimental studies showed that the drugs were not effective in reducing mortality (RR 1.1, 95%CI 1.0-1.3, I2 = 0.0%), need for intensive care services (OR 1.1, 95%CI 0.9-1.4, I2 = 0.0%), virological cure (OR 1.5, 95%CI 0.5-4.4, I2 = 39.6%) or disease exacerbation (OR 1.2, 95%CI 0.3-5.9, I2 = 31.9%) but increased the odds of adverse events (OR 12,3, 95%CI 2.5-59.9, I2 = 76.6%).

Conclusion: There is conclusive evidence that CQ and HCQ, with or without Azithromycin are not effective in treating COVID-19 or its exacerbation.

Registration: PROSPERO: CRD42020191353.

Keywords: Adverse events; COVID-19; Chloroquine; Disease worsening; Efficacy; Hydroxychloroquine; ICU; Mortality; Virological cure.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Antiviral Agents / therapeutic use
  • COVID-19 Drug Treatment*
  • Chloroquine / adverse effects
  • Humans
  • Hydroxychloroquine* / adverse effects
  • SARS-CoV-2
  • Systematic Reviews as Topic
  • Treatment Outcome


  • Antiviral Agents
  • Hydroxychloroquine
  • Chloroquine