Among Patients with COVID-19, should Remdesivir be Used for Treatment? A Systematic Review and Meta-analysis.

BACKGROUND

Remdesivir is an intravenously administered antiviral drug that inhibits RNA-dependent RNA polymerase. In vitro studies have shown that remdesivir can inhibit the growth of the COVID-19 virus in infected Vero cells and can inhibit infection in human cell lines.

OBJECTIVE

To determine the efficacy and safety of remdesivir in treating patients with COVID-19 infection.

METHODS

A systematic search of electronic medical literature databases was done from inception until September 4, 2022. Search for ongoing studies and preprints was also done. Risk of bias assessment was done using Cochrane risk of bias tool version 2.0. Measures of effect used were relative risk (RR) and 95% confidence interval (CI). Subgroup analysis by disease severity was preplanned. The estimates for efficacy and safety of remdesivir was calculated using Review Manager 5.4 software.

RESULTS

Nine randomized controlled trials with 13,085 participants were identified. Eight of the included studies recruited confirmed COVID-19 patients needing hospitalization, while one study limited recruitment to non-hospitalized patients. Remdesivir showed significant benefit for outpatients with mild to moderate disease with at least one risk factor for disease progression in terms of COVID 19-related hospitalization (RR 0.13 95% CI 0.03 to 0.59), all-cause hospitalization (RR 0.28, 95% CI 0.10 to 0.75), and need for medically-attended visits (RR 0.19, 95% CI 0.07 to 0.56). For hospitalized patients, remdesivir had a slight benefit in reducing all-cause mortality at day 28 (RR 0.90, 95% CI 0.83 to 0.98). Subgroup analysis by disease severity showed a trend towards reduction in mortality among those with severe disease (RR 0.61, 95% CI 0.35 to 1.07), with no effect on those with critical disease (RR 0.96, 95% CI 0.87 to 1.04), and inconclusive effect for those with mild-moderate disease (RR 0.74, 95% CI 0.49 to 1.11). Remdesivir showed benefit in decreasing clinical deterioration (RR 0.75, 95% CI 0.61 to 0.89), improving recovery rate (RR 1.07, 95% CI 1.01 to 1.13), and reducing the need for mechanical ventilation (RR 0.68, 95% CI 0.51 to 0.90). There was inconclusive effect on the need for ICU admission (RR 0.98, 95% CI 0.43 to 2.22). No increased risk of adverse events (RR 0.98, 95% CI 0.91 to 1.06), including serious adverse events (RR 0.77, 95% CI 0.57 to 1.03), was seen.

DISCUSSION

Based on the available evidence, remdesivir shows benefit in the treatment for patients with mild, moderate, and severe COVID-19 infection. However, there was no benefit in mortality noted among those with critical disease requiring mechanical ventilation. Remdesivir demonstrated a good safety profile, with no increased risk of adverse events compared to control. These results are consistent with the international agencies' recommendations for the use of remdesivir among patients with mild, moderate or severe COVID-19 infection, but not for those with critical infection.

CONCLUSION

Current evidence supports the use of remdesivir as treatment for selected patients with COVID-19.