We reported our systematic review according to 2009 PRISMA guidelines [11]. Inverse variance random effect meta-analyses were performed to evaluate effect of HCQ vs. control or SoC on outcomes when outcome data was available for at least two RCTs judged to have homogeneous study characteristics. Effects of meta-analyses were reported as relative risks (RR) for dichotomous outcomes; we also calculated their 95% confidence intervals (CIs). CIs of effects were adjusted with the Hartung-Knapp method [12], and the between study variance tau2 was calculated with the Paule-Mandel method [13]. Heterogeneity of effects among studies was quantified with the I2 statistic (an I2 > 60% means high heterogeneity). We pre-specified subgroup analyses by type of control and RoB; the p for interaction test <0.05 indicated effect modification by subgroup. The meta package of R 3.5.1 (www.r-project.org, accessed on 10 December 2020) was used for meta-analyses. The quality of evidence was evaluated using the GRADE methodology, which covers 5 aspects: risk of bias, inconsistency, indirectness, imprecision and publication bias [14]. Quality of evidence was evaluated per outcome and described in summary of findings (SoF) tables; GRADEpro GDT was used to create SoF tables [15].

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