Comparative efficacy and safety of anti-infective drugs for patients with mild to severe COVID-19: A systematic review and network meta-analysis of randomized controlled trials.

Background: Different anti-infective drugs have been proposed for the treatment of patients with COVID-19. We carried out a network meta-analysis to assess their relative efficacy and safety. Methods: We searched relevant databases for all randomized controlled trials that reported the efficacy and or safety of any anti-infective drugs published up to April 30, 2022 for different outcomes. We did both pairwise and network meta-analysis with 95% confidence intervals using a fixed-effect model. We assessed studies for quality of evidence using an extension of the standard Grading of Recommendations, Assessment, Development and Evaluation approach considering P<0.05 to be statistically significant. Results: We included 68 RCTs for 27,680 participants on 22 anti-infective drugs. For clinical recovery at 14 days Ivermectin (OR= 3.00, 95%CI: [1.82; 4.96]; p < 0.0001; moderate certainty evidence), Baricitinib plus Remdesivir (OR= 2.20, 95%CI: [1.35; 3.53]; p = 0.005; low certainty evidence), and Favipiravir (OR= 2.16, 95%CI: [1.27; 3.68]; p = 0.004; moderate certainty evidence) were statistically effective than standard of care. There was no statistically significant difference between treatments for the viral clearance at 14 days outcome and standard of care. In terms of death outcome, only combined therapy of Baricitinib and Remdesivir showed statistically significant risks of ratio (RR= 0.47, 95%CI: [0.23; 0.99]; p = 0.03). Arbidol (RR= 0.46, 95% CI: [0.23; 0.95]; p = 0.04) was statistically safe drug than standard of care. Conclusion: This Network Meta-analysis suggests that Baricitinib plus Remdesivir is more effective than the other anti-infective drugs in treating patients with COVID-19 in terms of clinical recovery at 14 days, mortality and adverse events outcomes.