Molnupiravir for treatment of adults with mild or moderate COVID-19: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND: The effects of molnupiravir in treating patients with non-severe COVID-19 remain uncertain. OBJECTIVES: To evaluate the efficacy and safety of molnupiravir in adult patients with mild or moderate COVID-19. DATA SOURCES: PubMed, Embase, CENTRAL, Web of Science, and WHO COVID-19 database up to 27 December 2022. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials with no language restrictions. PARTICIPANTS: Adults with mild or moderate COVID-19. INTERVENTIONS: Molnupiravir against standard care or placebo. ASSESSMENT OF RISK OF BIAS: We used a revision of RoB-2 criteria. METHODS OF DATA SYNTHESIS: Outcomes were mortality, hospital admission, viral clearance, time to viral clearance, time to symptom resolution or clinical improvement, any adverse events, and serious adverse events. We performed DerSimonian-Laird random-effects meta-analyses to summarize the evidence and evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Nine randomized controlled trials enrolling 30 472 patients proved eligible. Majority of patients were outpatients, with a mean age ranging from 35 to 56.6 years. In adult patients with mild or moderate COVID-19, molnupiravir probably reduces mortality (relative risk [RR], 0.43; 95% CI, 0.20–0.94; risk difference [RD], 0.1% fewer; moderate certainty) and the risk of hospital admission (RR, 0.67; 95% CI, 0.45–0.99; RD, 1.4% fewer; moderate certainty) and may reduce time to viral clearance (mean difference, −1.81 days; 95% CI, −3.31 to −0.31; low certainty) and time to symptom resolution or clinical improvement (mean difference, −2.39 days; 95% CI, −3.71 to −1.07; low certainty). Molnupiravir probably increases the rate of viral clearance (RR, 3.47; 95% CI, 2.43–4.96; RD 16.1% more; moderate certainty) at 7 days (±3 days) and likely does not increase serious adverse events (RR, 0.84; 95% CI, 0.61–1.15; RD 0.1% fewer; moderate certainty). CONCLUSIONS: In adult patients with mild or moderate COVID-19, molnupiravir likely reduces mortality and risk of hospital admission probably without increasing serious adverse events.