Use of hydroxychloroquine and chloroquine in patients with COVID-19: a meta-analysis of randomized clinical trials

Pathog Glob Health. 2021 May;115(3):139-150. doi: 10.1080/20477724.2021.1884807. Epub 2021 Feb 11.


COVID-19 has quickly become a public health problem worldwide, and treatment for this new disease is needed. Hydroxychloroquine is an antimalarial that in vitro studies have shown action against SARS-CoV-2, which is why it has been the target of clinical studies with conflicting results. Therefore, the aim of this systematic review was to assess the association of hydroxychloroquine use with the virological cure, clinical recovery, mortality, and development of adverse effects in patients with COVID-19. PubMed, Cochrane Library, and Lilacs were searched until 7 January 2021, for randomized clinical trials with COVID-19 patients treated with hydroxychloroquine or chloroquine. Of the 130 studies found, 12 met the inclusion criteria. Compared to the patient's control group, the risk ratio (RR) for the virological cure and clinical recovery with hydroxychloroquine or chloroquine use was 1.04 (95%CI 0.91-1.17) and 1.03 (95%CI 0.92-1.13), respectively. Hydroxychloroquine (with or without azithromycin) was also not associated with mortality (RR = 1.09, 95%CI 0.98-1.20). Treatment with hydroxychloroquine was associated with any adverse effects (RR = 1.50, 95%CI 1.18-1.81). Hydroxychloroquine or chloroquine use did not have a significant effect on virological cure, the time of clinical recovery, and improvement in survival in COVID-19 patients. However, patients who used hydroxychloroquine showed an increase in adverse effects.

Keywords: Chloroquine; SARS-CoV-2; coronavirus; hydroxychloroquine; meta-analysis.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use
  • COVID-19 / drug therapy*
  • COVID-19 / mortality
  • COVID-19 / virology
  • Chloroquine / adverse effects
  • Chloroquine / therapeutic use*
  • Female
  • Humans
  • Hydroxychloroquine / adverse effects
  • Hydroxychloroquine / therapeutic use*
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / physiology
  • Treatment Outcome


  • Antiviral Agents
  • Hydroxychloroquine
  • Chloroquine

Supplementary concepts

  • COVID-19 drug treatment

Grant support

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.