COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Treatment Elavarasi A, Prasad M, Seth T, et al. Chloroquine and Hydroxychloroquine for the Treatment of COVID-19: a Systematic Review and Meta-analysis. J Gen Intern Med. 2020 Nov;35(11):3308-3314. doi: 10.1007/s11606-020-06146-w. Epub 2020 Sep 3.

BACKGROUND: There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain.

OBJECTIVE: We performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19.

METHODS: Two reviewers searched for published and pre-published relevant articles between December 2019 and 8 June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa Scale. The quality of evidence was graded as per the GRADE approach.

RESULTS: We reviewed 12 observational and 3 randomized trials which included 10,659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66-1.46], time to fever resolution (mean difference - 0.54 days (- 1.19-011)) or clinical deterioration/development of ARDS with HCQ [RR 0.90 95% CI 0.47-1.71]. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes.

AUTHORS' CONCLUSION: The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19.

Discipline / Specialty Area Score
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Hospital Doctor/Hospitalists
Internal Medicine
Comments from MORE raters

Family Medicine (FM)/General Practice (GP) rater

Once again, the pressure to do something is enormous and understandable, however, the sensible thing to do is not to insist when the evidence of risk to harm jumps before benefit.

General Internal Medicine-Primary Care(US) rater

After multiple studies this summarizes what we all have come to know. They don't work on this virus!

Hospital Doctor/Hospitalists rater

Recently new evidence for this topic, the RECOVERY ISRCTN study published online in the NEJM, was published. As is always the case with the meta analyses, I'm curious to know what exclusions were made in the first stage of the study selection (Figure 1). Although the sample size was insufficient for a meta analysis, the results seem highly plausible. In the figure 4, the left and right sides are swapped, which confuses the readers. Fatal arrhythmias have probably been investigated in more studies; although, the investigators examined in only two cohort studies.

Respirology/Pulmonology rater

This is an excellent review. Only missing is an evaluation of the severity of the disease in the different studies.