Impact of Early Oral Antiviral Use for Outpatients With COVID-19 on Healthcare Utilization and Recovery (ANCHOR-02)

OBJECTIVES: To evaluate the associations of early-phase oral antivirals with recovery in outpatients with COVID-19, regardless of baseline risk for severe disease, during the SARS-CoV-2 Omicron JN.1-/KP.3-dominant epidemic era. METHODS: This nationwide, multi-institutional (51 acute-care hospitals in Japan), prospective, registry-based cohort study enrolled outpatients aged ≥12 years with laboratory-confirmed COVID-19 within 5 days of symptom onset (February 1-October 31, 2024). Participants were compared between those with and without oral antiviral use at enrollment (ensitrelvir, nirmatrelvir, or molnupiravir) for medical re-consultation, failure to return to usual health, and work productivity and activity impairment through Day 28. Analyses were conducted among participants with complete baseline covariates and valid Day 28 outcome assessments and were adjusted for pre-specified baseline covariates. RESULTS: Baseline characteristics were generally comparable between groups (efficacy analysis population: antiviral n=2271; no antiviral n=5768). Overall re-consultation rates tended to be lower in the antiviral group (adjusted risk ratio [aRR] 0.93; 95% CI 0.83-1.04). Antiviral use was associated with lower rates of failure to return to usual health (aRR 0.76; 95% CI 0.70-0.82) and with improvements in presenteeism, overall work impairment, and activity impairment. CONCLUSIONS: Early-phase oral antiviral use was associated with more favorable patient-reported and functional recovery outcomes, with a trend toward reduced healthcare utilization. These findings may have broader societal implications beyond traditional virological and disease progression endpoints.