Efficacy and Safety of Hydroxychloroquine and Chloroquine for COVID-19: A systematic review [preprint]

Abstract

BACKGROUND: Hydroxychloroquine and chloroquine are widely used to treat hospitalized COVID-19 patients primarily based on antiviral activity in in vitro studies. Our objective was to systematically evaluate their efficacy and safety in hospitalized patients with COVID-19. METHODS: We systematically reviewed PubMed, ClinicalTrials.gov, and Medrxviv for studies of hydroxychloroquine and chloroquine in COVID-19 hospitalized patients on April 26, 2020. We evaluated the quality of trials and observational studies using the Jadad criteria and Newcastle Ottawa Scale, respectively. RESULTS: After a review of 175 citations, we included 5 clinical trials (total of 345 patients), 9 observational studies (n = 2529), and 6 additional studies (n = 775) reporting on the QT interval. Three studies reported treatment benefits including two studies reporting benefit on virologic outcomes, which was statistically significant in one study, and another reported significant improvement on cough symptoms. Three studies reported that treatment was potentially harmful, including an significantly increased risk of mortality in two studies and increased need for respiratory support in another. Eight studies were unable to detect improvements on virologic outcomes (n = 3) or pneumonia or transfer to ICU/death (n = 5). The proportion of participants with critical QTc intervals of ≥ 500 ms or an increase of ≥ 60 ms from baseline ranged from 8.3% to 36% (n = 8). One clinical trial and six observational studies were of good quality. The remaining studies were of poor quality. CONCLUSIONS: Our systematic review of reported clinical studies did not identify substantial evidence to support the efficacy of hydroxychloroquine or chloroquine in hospitalized COVID-19 patients and raises questions about potential harm from QT prolongation and increased mortality.