Real-world Efficacy of Ensitrelvir in Hospitalized Patients with COVID-19 in Japan: A Retrospective Observational Study

Background : The coronavirus disease 2019 (COVID-19) pandemic necessitates continuously evaluating antiviral treatments, especially for high-risk groups, including older individuals. This study aimed to compare the efficacy of three antiviral drugs, including remdesivir, molnupiravir, and ensitrelvir, in hospitalized patients, focusing on outcomes such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen levels, hospitalization duration, and fever resolution. Methods : This retrospective observational study was conducted at Yoshida Hospital, Asahikawa city, Japan, enrolling 154 patients who received antiviral treatment upon COVID-19 diagnosis from July 1, 2022 to September 15, 2023. The diagnosis was confirmed by proprietary antigen tests or loop-mediated isothermal amplification assays. Patients who received treatment outside the hospital or with consistently negative antigen results were excluded. Drug administration was determined by attending physicians, considering oral administration challenges and renal dysfunction. The data were statistically analyzed using an unpaired two-tailed Student’s t-test and one-way analysis of variance complemented by the Tukey post-hoc test for detailed group comparisons. Results : No significant differences were observed in the initial antigen levels among the treatment groups. By day 10, the ensitrelvir group showed lower antigen levels than did the other groups, but not significantly. The ensitrelvir group had a higher antigen-negative conversion rate and a significantly shorter hospital stay than did the molnupiravir group. However, no significant differences were noted in the fever resolution time among the groups. Conclusion : This study suggests the potential benefits of ensitrelvir in reducing antigen levels and hospitalization duration. However, the overall efficacy of the antiviral agents for symptomatic relief appears similar. These findings underscore the need for further research to optimize COVID-19 management by considering personalized treatment approaches and long-term outcomes.