Publication date: Jul 01, 2025

This study aims to assess the comparative clinical effectiveness of the 3-chymotrypsin-like protease (3CLpro) inhibitors simnotrelvir-ritonavir and nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the omicron wave in China. The retrospective analysis of data from adult hospitalized patients with COVID-19 treated with either simnotrelvir-ritonavir or nirmatrelvir-ritonavir as antiviral treatment strategies will be conducted to determine any differences in clinical outcomes between the two drugs. This study involved a total of 585 participants, with 264 in the simnotrelvir group and 321 in the nirmatrelvir group. Following propensity score matching, there were 186 individuals in each group. There was no statistically significant difference in the cumulative risk of the composite disease progression, all-cause death, and respiratory support at 28 days following initiation of drug exposure between the two groups (p > 0. 05). However, the simnotrelvir group exhibited more cases of clinical improvement compared to the nirmatrelvir group (33. 602 events per 1000 person-days vs. 30. 913 events per 1000 person-days), with a better cumulative incidence in the simnotrelvir group (p 

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