Efficacy and Safety of Simnotrelvir-Ritonavir Compared With Nirmatrelvir-Ritonavir in the Treatment of COVID-19: Real-World Evidence From a Retrospective Cohort Study During the Prevalence of the Omicron EG.5 Variant.

Publication date: Jul 03, 2025

The rapid spread of the coronavirus-2019 (COVID-19) Omicron EG. 5 variant poses challenges to existing treatment strategies, and comparative real-world evidence between simnotrelvir-ritonavir and nirmatrelvir-ritonavir remains limited. We conducted a single-center retrospective study from July 01 to December 31, 2023, involving outpatient-diagnosed COVID-19 patients. We performed a descriptive analysis of epidemiologic characteristics, followed by regression analysis to identify key factors. Efficacy and safety differences between simnotrelvir-ritonavir and nirmatrelvir-ritonavir were then compared. A total of 545 patients were included, with 93. 21% presenting with general symptoms, 88. 81% with respiratory symptoms, 10. 28% with gastrointestinal symptoms, and 9. 36% with cardiovascular symptoms. Factors associated with delayed recovery included a BMI over 25 kg/m (P = 0. 004), and symptoms lasting more than 3 days at presentation (P = 0. 004). The efficacy of simnotrelvir-ritonavir and nirmatrelvir-ritonavir was comparable, with mean days to symptom recovery of 5. 11 and 4. 22 days, respectively. However, simnotrelvir-ritonavir had a higher incidence of adverse events (20. 59%) compared to nirmatrelvir-ritonavir (6. 69%), primarily gastrointestinal disorders. During the Omicron EG. 5 epidemic, general and respiratory symptoms predominated, with delayed recovery associated with being overweight, late treatment initiation, and multiple comorbidities. Simnotrelvir-ritonavir and nirmatrelvir-ritonavir demonstrated comparable efficacy, while simnotrelvir-ritonavir had a poorer safety profile.

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