In a subpopulation of patients who self-reported a high score for 14 COVID-19 symptoms at baseline, the overall risk of the presence of long COVID (at least two consecutive reports of the same symptom from among these 14 symptoms as of the time of the last available patient diary (e.g., Day 21 to Day 169), in the 125 mg ensitrelvir group significantly decreased compared with placebo (14.5% and 26.3% reported consecutive symptoms in the 125 mg ensitrelvir and placebo groups, respectively, 45% relative risk reduction, p<0.05). Additionally, the overall risk of reporting four neurological symptoms of long COVID at Day 85 or Day 169 in the 125 mg ensitrelvir group significantly decreased compared with placebo (29.4% and 44.0% reported symptoms at either Day 85 or Day 169 in the 125 mg ensitrelvir and placebo groups, respectively, 33% relative risk reduction, p<0.05). In an overall population of patients, 125 mg ensitrelvir group showed the same declining trend, 25% (p=0.1774) and 26% (p<0.05) relative risk reduction versus placebo for the 14 COVID-19 symptoms and the four neurological symptoms, respectively.