COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Treatment Chen C, Pan K, Wu B, et al. Safety of hydroxychloroquine in COVID-19 and other diseases: a systematic review and meta-analysis of 53 randomized trials. Eur J Clin Pharmacol. 2020 Aug 11. pii: 10.1007/s00228-020-02962-5. doi: 10.1007/s00228-020-02962-5.

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.

Discipline / Specialty Area Score
Emergency Medicine
Intensivist/Critical Care
General Internal Medicine-Primary Care(US)
Infectious Disease
Family Medicine (FM)/General Practice (GP)
Comments from MORE raters

Emergency Medicine rater

This manuscript is a systematic review and meta-analysis in order to assess the risk of adverse effects associated with the use of Hydroxychloroquine. As a vascular surgeon, I find this topic is not directly related to my expertise, however, considering that many doctors are being invited to act on the front line against coronavirus, the content of this article is relevant. Particularly, if I had not read the article, I would not have known about the adverse effects of hydroxychloroquine related to the gastrointestinal system and skin disorders, since the most reported events concern cardiotoxicity and retinopathy. The methodology and possible biases were clearly described. One criticism is pertinent in relation to the abstract: the results were summarized to the adverse effects for which the hydroxychloroquine group presented an increased risk, forgetting to mention the effects for which no statistically significant differences were found.

Emergency Medicine rater

This is a reasonably designed meta-analysis of adverse of effects of hydroxychlorquine use in treating COVID and all-other diseases. Briefly, there is a statisical and clincally important risk of adverse effects associated with HCQ use for any disease, including COVID. They were unable to determine if there was a difference in serious adverse effects. They did not detect any publication bias, but also did not preform sub-analyis for COVID only studies. There is probably is large amount of selection bias in these studies. Further analysis of the COVID studies results would also have been useful.

General Internal Medicine-Primary Care(US) rater

Cloroquine side efffect, may be important? This analysis looked primarily at patients treated with cloroquine and derivatives for non-Covid related illness. The pressing questions relate to the benefit/toxicity of these agents for the prevention/treatment of Covid related illness. There are no answers here.

Infectious Disease rater

This article adds little to what is already known about the use of hydroxychloroquine in the context of Covid-19.