COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Treatment Fiolet T, Guihur A, Rebeaud ME, et al. Effect of hydroxychloroquine with or without azithromycin on the mortality of coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis. Clin Microbiol Infect. 2021 Jan;27(1):19-27. doi: 10.1016/j.cmi.2020.08.022. Epub 2020 Aug 26.

BACKGROUND: Hydroxychloroquine or chloroquine with or without azithromycin have been widely promoted to treat coronavirus disease 2019 (COVID-19) following early in vitro antiviral effects against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

OBJECTIVE: The aim of this systematic review and meta-analysis was to assess whether chloroquine or hydroxychloroquine with or without azithromycin decreased COVID-19 mortality compared with the standard of care.

DATA SOURCES: PubMed, Web of Science, Embase Cochrane Library, Google Scholar and MedRxiv were searched up to 25 July 2020.

STUDY ELIGIBILITY CRITERIA: We included published and unpublished studies comparing the mortality rate between patients treated with chloroquine or hydroxychloroquine with or without azithromycin and patients managed with standard of care.

PARTICIPANTS: Patients =18 years old with confirmed COVID-19.

INTERVENTIONS: Chloroquine or hydroxychloroquine with or without azithromycin.

METHODS: Effect sizes were pooled using a random-effects model. Multiple subgroup analyses were conducted to assess drug safety.

RESULTS: The initial search yielded 839 articles, of which 29 met our inclusion criteria. All studies except one were conducted on hospitalized patients and evaluated the effects of hydroxychloroquine with or without azithromycin. Among the 29 articles, three were randomized controlled trials, one was a non-randomized trial and 25 were observational studies, including 11 with a critical risk of bias and 14 with a serious or moderate risk of bias. After excluding studies with critical risk of bias, the meta-analysis included 11 932 participants for the hydroxychloroquine group, 8081 for the hydroxychloroquine with azithromycin group and 12 930 for the control group. Hydroxychloroquine was not significantly associated with mortality: pooled relative risk (RR) 0.83 (95% CI 0.65-1.06, n = 17 studies) for all studies and RR = 1.09 (95% CI 0.97-1.24, n = 3 studies) for randomized controlled trials. Hydroxychloroquine with azithromycin was associated with an increased mortality (RR = 1.27; 95% CI 1.04-1.54, n = 7 studies). We found similar results with a Bayesian meta-analysis.

CONCLUSION: Hydroxychloroquine alone was not associated with reduced mortality in hospitalized COVID-19 patients but the combination of hydroxychloroquine and azithromycin significantly increased mortality.

Discipline / Specialty Area Score
Intensivist/Critical Care
Hospital Doctor/Hospitalists
Internal Medicine
Comments from MORE raters

Intensivist/Critical Care rater

It is important to work up the evidence coming out of the huge number of different types studies regarding COVID-19. This meta-analysis adds a big chunk of evidence leading to safer care of patients.

Intensivist/Critical Care rater

This is a very important review. This information is very crucial for every health professionals in the pandemic of COVID-19. The use of systematic ways in searching and appraising the articles are the strength of this review. The process of critical appraisal are very clearly described. The use of appropriate statistical analysis for evidences synthesis also important point in this review. This review showed that neither azythromycin and hydroxycholoroquine are beneficial for COVID patients. There is a strong need for further exploration for COVID proven therapy in the future.