Effectiveness and Safety of Hydroxychloroquine, Chloroquine, with or without Azithromycin in the Treatment of COVID-19: A Systematic Review and Meta-Analysis

Background: The outbreak of COVID-19 has caused a serious threat to the lives of people all over the world. At present, there is a lack of specific drugs for the treatment of COVID-19, and the development of effective vaccines is also in progress. With the increasing number of patients worldwide, how to choose safe and effective drugs to treat COVID-19 is imminent. Purpose: To evaluate the safety and effectiveness of hydroxychloroquine, chloroquine, and azithromycin in the treatment of COVID-19. Methods: We conducted a comprehensive search by combining the MeSH and free words on Pubmed, Embase, Cochrane, Web of Science, medRxiv, and bioRxiv. The type of study is limited to clinical trials and observational studies. We used the Jadad scale and the American Agency for Health Research and Quality tool to evaluate the quality of the literature. A meta-analysis was undertaken using STATA version 15.0. Results: A total of 14 related articles including 5048 subjects were included in the study, of which 3 articles were randomized controlled studies and 11 articles were observational cohort studies. In terms of drug effectiveness, compared with patients receiving neither drug, there were no significant differences in in-hospital mortality, mechanical ventilation rate, ICU admission rate, and negative conversion rate of SARS-COV-2 for patients receiving hydroxychloroquine or chloroquine. In terms of drug safety, compared with patients receiving neither drug, adverse drug events were no significant differences in patients receiving hydroxychloroquine or chloroquine. In addition, our study also found that compared with hydroxychloroquine or chloroquine treatment alone, combined with azithromycin treatment does not increase the risk of QT interval prolongation and the mortality of hospitalized patients. Conclusions: Treatment with hydroxychloroquine, chloroquine, or azithromycin, compared with patients receiving neither drug, was not significant differences in drug effectiveness and safety. However, the interpretation of these results may be limited by the small samples and observational studies. So, it is very necessary to conduct more large-scale randomized, double-blind, prospective controlled studies.