This phase 2-3, double-blind, placebo-controlled trial evaluated the efficacy and safety of simnotrelvir plus ritonavir in treating adult patients with mild-to-moderate COVID-19. The primary endpoint was the time to sustained resolution of symptoms, defined as the absence of 11 COVID-19-related symptoms for 2 consecutive days. A total of 1208 patients were enrolled at 35 sites in China, with 603 assigned to simnotrelvir plus ritonavir and 605 to placebo. The median time to sustained resolution of symptoms was significantly shorter in the simnotrelvir group (180.1 hours) compared to the placebo group (216.0 hours). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group (−1.51 log10 copies per milliliter) than in the placebo group (−1.24 log10 copies per milliliter). The incidence of adverse events was higher in the simnotrelvir group (29.0% vs. 21.6%), but most were mild or moderate. The study concluded that early administration of simnotrelvir plus ritonavir shortened the time to symptom resolution without significant safety concerns.This phase 2-3, double-blind, placebo-controlled trial evaluated the efficacy and safety of simnotrelvir plus ritonavir in treating adult patients with mild-to-moderate COVID-19. The primary endpoint was the time to sustained resolution of symptoms, defined as the absence of 11 COVID-19-related symptoms for 2 consecutive days. A total of 1208 patients were enrolled at 35 sites in China, with 603 assigned to simnotrelvir plus ritonavir and 605 to placebo. The median time to sustained resolution of symptoms was significantly shorter in the simnotrelvir group (180.1 hours) compared to the placebo group (216.0 hours). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group (−1.51 log10 copies per milliliter) than in the placebo group (−1.24 log10 copies per milliliter). The incidence of adverse events was higher in the simnotrelvir group (29.0% vs. 21.6%), but most were mild or moderate. The study concluded that early administration of simnotrelvir plus ritonavir shortened the time to symptom resolution without significant safety concerns.