COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

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Treatment Elsawah HK, Elsokary MA, Elrazzaz MG, et al. Hydroxychloroquine for treatment of nonsevere COVID-19 patients: Systematic review and meta-analysis of controlled clinical trials. J Med Virol. 2021 Mar;93(3):1265-1275. doi: 10.1002/jmv.26442. Epub 2020 Sep 29.

Being a pandemic and having a high global case fatality rate directed us to assess the evidence strength of hydroxychloroquine efficacy in treating coronavirus disease-2019 (COVID-19) arising from clinical trials and to update the practice with the most reliable clinical evidence. A comprehensive search was started in June up to 18 July, 2020 in many databases, including PubMed, Embase, and others. Of 432 studies found, only six studies fulfilled the inclusion criteria, which includes: clinical trials, age more than 12 years with nonsevere COVID-19, polymerase chain reaction-confirmed COVID-19, hydroxychloroquine is the intervention beyond the usual care. Data extraction and bias risk assessment were done by two independent authors. Both fixed-effect and random-effect models were utilized for pooling data using risk difference as a summary measure. The primary outcomes are clinical and radiological COVID-19 progression, severe acute respiratory syndrome coronavirus-2 clearance in the pharyngeal swab, and mortality. The secondary outcomes are the adverse effects of hydroxychloroquine. Among 609 COVID-19 confirmed patients obtained from pooling six studies, 294 patients received hydroxychloroquine and 315 patients served as a control. Hydroxychloroquine significantly prevents early radiological progression relative to control with risk difference and 95% confidence interval of -0.2 (-0.36 to -0.03). On the other hand, hydroxychloroquine did not prevent clinical COVID-19 progression, reduce 5-day mortality, or enhance viral clearance on days 5, 6, and 7. Moreover, many adverse effects were reported with hydroxychloroquine therapy. Failure of hydroxychloroquine to show viral clearance or clinical benefits with additional adverse effects outweigh its protective effect from radiological progression in nonsevere COVID-19 patients. Benefit-risk balance should determine the hydroxychloroquine use in COVID-19.

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

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

A meta-analysis of studies of hydroxychloroquine in the treatment of Covid-19 shows improvement in radiological progression of disease but NOT clinical benefit. Since there is well recognized toxicity of hydroxychloroquine, the treatment cannot be recommended for use in treatment or prevention.

General Internal Medicine-Primary Care(US) rater

I feel that most of this information is available by searching the NEJM COVID updates as well as the BMJ. Also, there are many grammatical errors in the text which I have highlighted.

Internal Medicine rater

Results on efficacy are probably familiar to readers. In terms of adverse effects, there is quite striking difference in adverse effects between Hydroxychloroquine and placebo arms in one study included in this meta-analysis. Serious adverse effects in this particular study were comparable between both arms, though. Interestingly, in this particular study cited, in HCQ arm there appears to be more patients with gastrointestinal than any adverse effects (88% vs 72%).