COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Treatment Hernandez AV, Roman YM, Pasupuleti V, et al. Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review. Ann Intern Med. 2020 Aug 18;173(4):287-296. doi: 10.7326/M20-2496. Epub 2020 May 27.

BACKGROUND: Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

PURPOSE: To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19).

DATA SOURCES: PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints,, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020.

STUDY SELECTION: Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection.

DATA EXTRACTION: Independent, dually performed data extraction and quality assessments.

DATA SYNTHESIS: Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis. Evidence was conflicting and insufficient regarding the effect of hydroxychloroquine on such outcomes as all-cause mortality, progression to severe disease, clinical symptoms, and upper respiratory virologic clearance with antigen testing. Several studies found that patients receiving hydroxychloroquine developed a QTc interval of 500 ms or greater, but the proportion of patients with this finding varied among the studies. Two studies assessed the efficacy of chloroquine; 1 trial, which compared higher-dose (600 mg twice daily for 10 days) with lower-dose (450 mg twice daily on day 1 and once daily for 4 days) therapy, was stopped owing to concern that the higher dose therapy increased lethality and QTc interval prolongation. An observational study that compared adults with COVID-19 receiving chloroquine phosphate, 500 mg once or twice daily, with patients not receiving chloroquine found minor fever resolution and virologic clearance benefits with chloroquine.

LIMITATION: There were few controlled studies, and control for confounding was inadequate in observational studies.

CONCLUSION: Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting.

PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

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

Emergency Medicine rater

This information is changing so rapidly, however, the balance of evidence has prompted the WHO to suspend routine clinical use and discourage further RCTs, so the paper is of importance.

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

Information about this subject is changing and new data appears every now and then. Political issues have been raised as well. Most of the studies were not very solid and not without a lot of bias as was shown even in the systemic review of this study.

General Internal Medicine-Primary Care(US) rater

This is a good review of the current state of our knowledge, which is admittedly in its early stages. There is no new information for those who regularly keep up with this topic.

Intensivist/Critical Care rater

This is a clinically relevant and timely living systematic review. The limitations include the lack of registration/publication of the protocol and the missing assessment of the certainty of evidence a. m. GRADE.

Internal Medicine rater

A living systematic review that will be updated every month with a table of evidence that evidence! Very important in these times of 'poor scientific publications.'

Public Health rater

This is relevant information since it is still being used despite its toxicity (the FDA withdrew its recommendation this week).