Molnupiravir for high-risk adults with COVID-19: Target trial emulation in a Japanese cohort

Evidence on the effectiveness of molnupiravir for high-risk adults in a highly vaccinated Asian population is sparse. In this study, we aimed to estimate the association between molnupiravir use and hospital admission or death in high-risk adults with COVID-19 during the Omicron era.

This retrospective cohort study included high-risk patients diagnosed with COVID-19 in Shimonoseki City between September 16, 2022, and May 8, 2023. The outcome was a composite of hospital admission or death within 28 days. Participants were categorized into two groups: those who used molnupiravir within 5 days of diagnosis and those who did not. The outcomes were compared using a Cox proportional hazards model. Treatment weighting was used to balance patient backgrounds between the groups, and the clone method with inverse probability of censoring weighting was used to adjust for informative censoring.

We analyzed 330 patients (190 females, 57.6 %) with a mean age of 68.6 years. The proportion of fully vaccinated and boosted patients was 82.9 % (155/187) in the molnupiravir group and 90.2 % (129/143) in the control group. The overall 28-day incidence of all-cause hospitalization and mortality was 5.2 % (17/330), with 3.2 % (6/187) in the molnupiravir group and 7.7 % (11/143) in the control group. Molnupiravir was associated with a decrease in hospital admissions or death within 28 days (weighted hazard ratio, 0.35 [95 % confidence intervals, 0.13 to 0.90]).

Molnupiravir was linked to fewer hospitalizations or deaths within 28 days compared to no treatment in highly vaccinated high-risk patients with COVID-19 in Japan.