Prevention of post COVID-19 condition by early treatment with ensitrelvir in the phase 3 SCORPIO-SR trial

This exploratory analysis of the double-blind, phase 3, SCORPIO-SR trial assessed the effect of ensitrelvir in preventing post coronavirus disease 2019 (COVID-19) condition (PCC). Patients with mild-to-moderate COVID-19 were randomized (1:1:1) within 120 h of symptom onset; received 5-day oral ensitrelvir 125 mg (375 mg on day 1), 250 mg (750 mg on day 1), or a matching placebo once daily; and were assessed for the severity of typical PCC symptoms using a self-administered questionnaire. In total, 341, 317, and 333 patients were assessed in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively (mean age, 35.6–36.5 years; men, 53.3%–58.3%). On days 85, 169, and 337, ensitrelvir 125-mg treatment showed 32.7% (95% confidence interval [CI]: 30.6, 66.1), 21.5% (95% CI: 37.3, 55.6), and 24.6% (95% CI: 43.7, 60.9) reductions versus placebo, respectively, in the risk of any of the 14 acute-phase COVID-19 symptoms (at least one mild, moderate, or severe symptom with general health not returning to the usual level). Ensitrelvir 250-mg treatment showed 10.9% (95% CI: 67.0, 52.8), 9.5% (95% CI: 56.6, 48.0), and 30.6% (95% CI: 36.2, 65.5) risk reductions versus placebo on days 85, 169, and 337, respectively. Risk reductions were observed in any of the 4 neurological symptoms and were more pronounced among patients with high acute-phase symptom scores at baseline and among those with a baseline body mass index ≥25 kg/m². Ensitrelvir treatment in the acute phase of COVID-19 may reduce the risk of various symptoms associated with PCC. Trial registration number: jRCT2031210350.