Effect of hydroxychloroquine with or without azithromycin on the mortality of COVID-19 patients: a systematic review and meta-analysis

The systematic review published recently in Clinical Microbiology and Infection was based on  29 articles [1]. All studies except one were conducted on hospitalized patients and evaluated the effects of hydroxychloroquine with or without azithromycin. Among the 29 articles, 3 were randomized controlled trials (RCT), one was a non-randomized trial and 25 were observational studies, including 10 with a critical risk of bias and 15 with a serious or moderate risk of bias. After excluding studies with critical risk of bias, the meta-analysis included 11,932 participants for the hydroxychloroquine group, 8,081 for the hydroxychloroquine with azithromycin group and 12,930 for the control group. Hydroxychloroquine was not significantly associated with mortality: pooled Relative Risk RR=0.83 (95% CI: 0.65-1.06, n=17 studies) for all studies and RR=1.09 (95% CI: 0.97-1.24, n=3 studies) for RCTs. Hydroxychloroquine with azithromycin was associated with an increased mortality: RR=1.27 (95% CI: 1.04-1.54, n=7 studies). We found similar results with a Bayesian meta-analysis.

Hydroxychloroquine alone was not associated with reduced mortality in hospitalized COVID-19 patients but the combination of hydroxychloroquine and azithromycin significantly increased mortality.