Abstract
BACKGROUND: This real-world study aimed to assess the effectiveness of novel oral antiviral agents in managing COVID-19 among high-risk patients during the Omicron JN.1 subvariant wave. METHODS: Data from the TriNetX US network were analyzed using a multi-institutional propensity score matching (PSM) analysis. High-risk non-hospitalized adults with COVID-19 were included, and patients receiving oral antiviral agents (study group) were compared to those not receiving antiviral agents (control group). Primary outcomes included all-cause emergency department (ED) visits, hospitalizations, or death within 30 days. RESULTS: Among 67,495 high-risk patients identified, 17,852 received oral antiviral agents (study group) and 49,643 did not (control group). After PSM, two matched cohorts of 17,847 patients each were established. The study group receiving antiviral agents exhibited a significantly lower risk of primary composite outcome during the 30-day follow-up period compared to the control group (HR, 0.77; 95% CI, 0.72-0.84). Regarding the secondary outcomes, the study group consistently exhibited a significantly lower risk of all-cause ED visits (4.2% vs. 5.4%; HR, 0.78; 95% CI, 0.71-0.86), hospitalization (2.8% vs. 3.3%; HR, 0.86; 95% CI, 0.77-0.97), and mortality (0.1% vs. 0.3%; HR, 0.17; 95% CI, 0.08-0.35) than the control group. Subgroup analyses showed consistent benefits across various demographic and clinical characteristics, except in individuals with booster vaccination. CONCLUSIONS: Oral antiviral agents significantly reduced the risk of adverse outcomes among high-risk COVID-19 patients during the Omicron JN.1 subvariant wave. These findings support the potential benefits of oral antiviral therapy in treating COVID-19, particularly in high-risk populations.