Impact of Early COVID‐19 Antiviral Therapy on the Incidence of Uveitis: A Retrospective Cohort Study Using the TriNetX Database

OBJECTIVE: To assess whether antivirals are associated with a reduced incidence of uveitis following COVID-19. METHODS: We conducted a multi-institutional, population-based retrospective cohort study of adults (≥ 18 years) diagnosed with COVID-19 between 2022 and 2024. Patients who received antiviral agents (Paxlovid, Molnupiravir, or Remdesivir) within 5 days of diagnosis were matched 1:1 with untreated controls using propensity score matching. Patients with pre-existing uveitis, early-onset uveitis within 5 days of the index date, or underlying systemic inflammatory or infectious diseases were excluded. The primary outcome was new-onset uveitis, with hazard ratios (HRs) calculated across follow-up intervals. RESULTS: After matching, 438,455 patients were included in both the antiviral and non-antiviral groups. Antiviral therapy was associated with a significantly lower risk of uveitis at 3 months (HR = 0.62, 95% CI: 0.45-0.87), 6 months (HR = 0.68, 95% CI: 0.54-0.87), 1 year (HR = 0.76, 95% CI: 0.64-0.91), 3 years (HR = 0.80, 95% CI: 0.70-0.92), and all duration (HR = 0.81, 95% CI: 0.71-0.93). Subgroup analysis revealed consistent benefit across all age groups, with females experiencing greater protection than males. Significant reductions in uveitis risk were observed among patients with diabetes (HR = 0.68, 95% CI: 0.52-0.89), hyperlipidemia (HR = 0.78, 95% CI: 0.65-0.95), and heart failure (HR = 0.52, 95% CI: 0.30-0.90). Among the antivirals, Paxlovid was associated with a significant risk reduction (HR = 0.83, 95% CI: 0.71-0.96), whereas Molnupiravir and Remdesivir showed no statistically significant effect. CEV classification did not show significant improvement. Besides, the risk reduction was evident regardless of prior COVID-19 vaccination status. CONCLUSIONS: Early antiviral treatment for COVID-19 such as Paxlovid, is associated with a reduced risk of uveitis. These findings suggest that, in addition to mitigating systemic disease progression, antiviral therapy may confer ocular protective effects, which could be especially meaningful for high-risk populations.