Abstract
BACKGROUND: Real-world data evaluating the effectiveness of nirmatrelvir-ritonavir across diverse age groups and vaccination statuses remain limited, particularly in East Asian populations. This study evaluates its effectiveness in reducing severe COVID-19 outcomes using a large, comprehensive nationwide healthcare database and to provide new evidence. METHOD: This retrospective observational cohort study involved outpatient COVID-19 patients diagnosed between 1 January 2022, and 1 December 2022, within Taiwan's National Health Insurance Research Database. Patients who received nirmatrelvir-ritonavir were compared with untreated patients. Primary outcomes include COVID-19-related hospitalization, ICU admission, invasive ventilatory support, death, and the composite outcome of hospital admission or death. RESULTS: A total of 2 300 131 nonhospitalized patients with confirmed COVID-19 between 1 January 2022 and 1 December 2022, including 530 807 patients treated with nirmatrelvir-ritonavir and 1 769 324 untreated patients. Treatment with nirmatrelvir-ritonavir was associated with a significantly lower risk of COVID-19-related hospitalization (hazard ratio 0.32 [95% CI .31-.34]), ICU admission (0.41 [.38-.45]), invasive ventilatory support (0.38 [.33-.43]), death (0.42 [.40-.45]), and the composite outcome of hospital admission or death (0.34 [.33-.35]). Effectiveness was consistent across subgroups stratified by age and vaccination status, with the greatest benefit observed in unvaccinated individuals and those aged ≥65 years with additional risk factors. CONCLUSIONS: In a large, nationally representative cohort, outpatient use of nirmatrelvir-ritonavir was associated with a significantly lower risk of severe COVID-19-related outcomes, regardless of age or vaccination status. These findings reinforce the clinical value of early antiviral treatment, particularly in aging and unvaccinated populations.