Efficacy and harms of remdesivir for the treatment of COVID-19: A systematic review and meta-analysis
Open Access
- 10 December 2020
- journal article
- review article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 15 (12), e0243705
- https://doi.org/10.1371/journal.pone.0243705
Abstract
Efficacy and safety of treatments for hospitalized COVID-19 are uncertain. We systematically reviewed efficacy and safety of remdesivir for the treatment of COVID-19. Studies evaluating remdesivir in adults with hospitalized COVID-19 were searched in several engines until August 21, 2020. Primary outcomes included all-cause mortality, clinical improvement or recovery, need for invasive ventilation, and serious adverse events (SAEs). Inverse variance random effects meta-analyses were performed. We included four randomized controlled trials (RCTs) (n = 2296) [two vs. placebo (n = 1299) and two comparing 5-day vs. 10-day regimens (n = 997)], and two case series (n = 88). Studies used intravenous remdesivir 200mg the first day and 100mg for four or nine more days. One RCT (n = 236) was stopped early due to AEs; the other three RCTs reported outcomes between 11 and 15 days. Time to recovery was decreased by 4 days with remdesivir vs. placebo in one RCT (n = 1063), and by 0.8 days with 5-days vs. 10-days of therapy in another RCT (n = 397). Clinical improvement was better for 5-days regimen vs. standard of care in one RCT (n = 600). Remdesivir did not decrease all-cause mortality (RR 0.71, 95%CI 0.39 to 1.28, I2 = 43%) and need for invasive ventilation (RR 0.57, 95%CI 0.23 to 1.42, I2 = 60%) vs. placebo at 14 days but had fewer SAEs; 5-day decreased need for invasive ventilation and SAEs vs. 10-day in one RCT (n = 397). No differences in all-cause mortality or SAEs were seen among 5-day, 10-day and standard of care. There were some concerns of bias to high risk of bias in RCTs. Heterogeneity between studies could be due to different severities of disease, days of therapy before outcome determination, and how ordinal data was analyzed. There is paucity of adequately powered and fully reported RCTs evaluating effects of remdesivir in hospitalized COVID-19 patients. Until stronger evidence emerges, we cannot conclude that remdesivir is efficacious for treating COVID-19.This publication has 21 references indexed in Scilit:
- Compassionate Use of Remdesivir for Patients with Severe Covid-19The New England Journal of Medicine, 2020
- Comparative Effectiveness of Combined Favipiravir and Oseltamivir Therapy Versus Oseltamivir Monotherapy in Critically Ill Patients With Influenza Virus InfectionThe Journal of Infectious Diseases, 2020
- A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19The New England Journal of Medicine, 2020
- Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trialThe Lancet, 2020
- Evaluation of the Efficacy and Safety of Intravenous Remdesivir in Adult Patients with Severe Pneumonia caused by COVID-19 virus Infection: study protocol for a Phase 3 Randomized, Double-blind, Placebo-controlled, Multicentre trialPublished by Research Square Platform LLC ,2020
- Arguments in favour of remdesivir for treating SARS-CoV-2 infectionsInternational Journal of Antimicrobial Agents, 2020
- RoB 2: a revised tool for assessing risk of bias in randomised trialsBMJ, 2019
- ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventionsBMJ, 2016
- GRADE guidelines: 3. Rating the quality of evidenceJournal of Clinical Epidemiology, 2011