Molnupiravir Use and 30-Day Hospitalizations or Death in a Previously Uninfected Nonhospitalized High-risk Population with COVID-19

Background: Clinical benefit of molnupiravir (MPV) in coronavirus disease 2019 (COVID-19)-infected subpopulations is unclear. Methods: We used a matched cohort study design to determine the rate of hospitalization or death within 30 days of COVID-19 diagnosis among MPV treated and untreated controls. Participants were nonhospitalized, previously uninfected Veterans with a first confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection between 1 January and 31 August 2022, who were prescribed MPV within 3 days of COVID-19 diagnosis, and matched individuals who were not prescribed MPV. Results: Among 1459 matched pairs, the incidence of hospitalization/death was not different among MPV treated versus untreated controls (48 vs 44 cases; absolute risk difference [ARD], 0.27; 95% confidence interval [CI],-.94 to 1.49). No benefit was observed among those >60 or ≤60 years old (ARD, 0.27; 95% CI,-1.25 to 1.79 vs ARD,-0.29; 95% CI,-1.22 to 1.80), those with specific comorbidities, or by vaccination status. A significant benefit was observed in asymptomatic but not in symptomatic persons (ARD,-2.80; 95% CI,-4.74 to-.87 vs ARD, 1.12; 95% CI-.31 to 2.55). Kaplan-Meier curves did not show a difference in proportion of persons who were hospitalized or died among MPV treated compared with untreated controls (logrank P =. 7). Conclusions: MPV was not associated with a reduction in hospitalization or death within 30 days of COVID-19 diagnosis. A subgroup of patients presenting without symptoms experienced a benefit.