Retrospective analysis on Nirmatrelvir versus Simnotrelvir for adults with moderate to severe COVID-19.

<bold>Background:</bold> Nirmatrelvir and Simnotrelvir are two oral 3CLpro inhibitors for treatment of COVID-19 in China, both being recommended in mild to moderately ill patients. Data on the benefits and comparisons of these drugs for patients with moderate to severe illness are lacking. <bold>Objective:</bold> To investigate the efficacy of two 3CLpro inhibitors in the treatment of adult patients with moderate to severe COVID-19. <bold>Methods:</bold> A retrospective analysis was performed on the hospitalized patients diagnosed with COVID-19 who received either Nirmatrelvir/ritonavir or Simnotrelvir/ritonavir between December 20, 2022, and November 31, 2023. The effects of the two drugs on symptom relief time, nucleic acid conversion time, adverse event, and improvement of patient QoL were assessed. <bold>Results:</bold> A total of 460 hospitalized patients were included, 76.96% being classified as severe cases. A total of 258 patients received Nirmatrelvir/ritonavir, 202 patients received Simnotrelvir/ritonavir. A total of 18 deaths identified (14 in Nirmatrelvir group and 4 in Simnotrelvir group). Among patients who received antiviral drugs within 5 days after symptom onset, time to symptom relief was slightly shorter in the Simnotrelvir group, with a shorter average time for body temperature recover (2.81 days vs 3.04 days), although the difference was not statistically significant. No serious drug-related adverse reactions occurred in either group. <bold>Conclusion:</bold> The overall efficacy of the two drugs is comparable, treatment choice should be based on the individual patient’s situation and resistance status. These findings provide reference information for clinicians when selecting antiviral treatment regimens.