Remdesivir for the treatment of COVID-19: a systematic review and meta-analysis

Abstract

Background: The benefits of remdesivir in the treatment of hospitalized patients with COVID-19 remain debated with the National Institutes of Health and the World Health Organization providing contradictory recommendations for and against use.

Objectives: To evaluate the role of remdesivir for hospitalized inpatients as a function of oxygen requirements.

Data sources: Beginning with our prior systematic review, we searched MEDLINE using PubMed from 15 January 2021 through 5 May 2022.

Study eligibility criteria: Randomised controlled trials; all languages.

Participants: All hospitalized adults with COVID-19.

Interventions: Remdesivir, in comparison to either placebo, or standard of care.

Assessment of risk of bias: We used the ROB-2 criteria.

Methods of data synthesis: The primary outcome was mortality, stratified by oxygen use (none, supplemental oxygen without mechanical ventilation, and mechanical ventilation). We conducted a frequentist random effects meta-analysis on the risk ratio scale and, to contextualize the probabilistic benefits, we also performed a Bayesian random effects meta-analysis on the risk difference scale. A ≥1% absolute risk reduction was considered clinically important.

Results: We identified eight randomized trials, totaling 10 751 participants. The risk ratio for mortality comparing remdesivir vs. control was 0.77 (95% CI, 0.5-1.19) in the patients who did not require supplemental oxygen; 0.89 (95% CI, 0.79-0.99) for nonventilated patients requiring oxygen; and 1.08 (95% CI, 0.88-1.31) in the setting of mechanical ventilation. Using neutral priors, the probabilities that remdesivir reduces mortality were 76.8%, 93.8%, and 14.7%, respectively. The probability that remdesivir reduced mortality by ≥ 1% was 77.4% for nonventilated patients requiring oxygen.

Conclusions: Based on this meta-analysis, there is a high probability that remdesivir reduces mortality for nonventilated patients with COVID-19 requiring supplemental oxygen therapy. Treatment guidelines should be re-evaluated.

Keywords: COVID-19; Coronavirus; Meta-analysis; Mortality; Remdesivir.

Fig. 1

PRISMA diagram for the systematic review and meta-analysis. RCT: Randomized controlled trial.

Fig. 2

Random effects meta-analysis stratified by oxygenation requirements. ∗Excludes patients already reported in SOLIDARITY 1 (NEJM 2020) and CATCO (CMAJ 2022); ∗∗Excludes patients reported in SOLIDARITY 1 (NEJM 2022). ACTT: Adaptive Covid-19 Treatment Trial. CATCO: Canadian Treatments for COVID-19.

Fig. 3

Probability density functions for combined posterior distributions of the included remdesivir trials. (a) Mechanical ventilation. (b) Supplemental oxygen without mechanical ventilation. (c) No oxygen support. AUC, area under the curve.