Effectiveness and Safety of Remdesivir in Patients with COVID-19: A Systematic Review and Meta-Analysis

Abstract Background: Remdesivir, a nucleoside analogue antiviral drug developed for Ebola, is approved by the US Food and Drug Administration for the treatment of COVID-19. However, the findings of randomised controlled trials (RCTs) and observational studies vary regarding the effectiveness of remdesivir. We aimed to comprehensively review the available evidence identify the effectiveness and safety of remdesivir in patients with COVID-19.Methods: Seven databases (PubMed, Web of Science, Embase, Wanfang database, SinoMed, Chinese National Knowledge Infrastructure and Chinese Science Journal Database) were searched for literatures published until November 2020.Following the PRISMA flow diagram, we included RCTs and prospective observational studies that reported the effectiveness and safety of remdesivir in patients with COVID-19. With extracting study details, as well as patient characteristics and outcomes, data were meta-analyzed by using Review Manager software version 5.4.1. Meta-analyses were conducted with fixed-effect model or random-effect model to calculate risk ratio (RR).Results: Four studies involving 2,279 patients were included in this meta-analysis. Compared with placebo, 10-day remdesivir was associated with significant increased clinical improvement on days 14 and 28 with RR 1.19 (95%CI 1.09-1.30) and RR 1.09 (95%CI 1.03-1.16). The clinical improvement of 5-day remdesivir was better than 10-day remdesivir on days 7 with RR 1.20 (95%CI 1.02-1.41), but the efficacy advantage of 5-day remdesivir disappeared on days 14 (RR 1.08; 95%CI 0.90-1.29). Remdesivir was associated with lower serious adverse events rates and grade 3 or 4 adverse events rates as compared with placebo with RR 0.75(95%CI 0.63-0.89) and RR 0.89(95%CI 0.80-0.99). Compared with 10-day remdesivir, 5-day remdesivir for patients with COVID-19 decreased the risk of serious adverse events rates and grade 3 or 4 adverse events rates with RR 0.65(95%CI 0.47-0.88) and RR 0.74 (95%CI 0.58-0.95). Conclusions: Our meta-analysis suggested that remdesivir would increase clinical improvement conditions and decrease serious adverse events on patients with COVID-19. 5-day remdesivir had the similar clinical effectiveness and mortality with 10-day remdesivir, and had lower serious adverse events rate. Comprehensive considering the cost and benefit, 5-day remdesivir may be a better therapeutic option if available medical resources are limited.