Effect of use of oral antiviral agents on reducing critical illness and mortality for patients with moderate to severe COVID-19

<bold>Objectives:</bold> To compare the clinical outcomes between the simnotrelvir/ritonavir and nirmatrelvir/ritonavir in patients with moderate to severe COVID-19. <bold>Methods:</bold> This retrospective cohort study included patients with COVID-19 patients who required hospitalization between 1 October 2022 and 15 January 2024. The primary outcomes were the development of critical illness, including intensive care unit admission, use of mechanical ventilation, or mortality. A multivariate logistic regression analysis was conducted to assess the varying risks of critical illness and mortality. A total of 531 COVID-19 patients were analyzed. Among them, 71 (13.4%) received simnotrelvir/ritonavir and 248 (46.7%) received nirmatrelvir/ritonavir. <bold>Results:</bold> There were significant reductions for critical illness (adjusted odds ratio[OR] 0.37 95% CI 0.20–0.71, P < 0.001) and mortality (adjusted OR 0.41, 95% CI 0.20–0.82, P < 0.001) in patients receiving oral antivirals compared with those who did not. No significant differences in critical illness were observed between simnotrelvir/ritonavir and nirmatrelvir/ritonavir. The SARS-CoV-2 nucleic acid or antigen shedding time was 5.0 (5.0, 9.0) days and 6.0 (5.0, 8.0) days in the simnotrelvir/ritonavir group and nirmatrelvir/ritonavir group, respectively. There were no statistical differences between the two groups (p=0.783). <bold>Conclusion:</bold> Administering simnotrelvir/ritonavir and nirmatrelvir/ritonavir reduced the risk of moderate to severe COVID-19 patients progressing to critical illness and mortality.