Effectiveness and Safety of Simnotrelvir/Ritonavir and Nirmatrelvir/Ritonavir in the Treatment of Moderate to Severe COVID-19

Abstract

Background and aim: Simnotrelvir/ritonavir and nirmatrelvir/ritonavir are major treatments for COVID-19, but their comparative efficacy and safety, especially in patients with moderate to severe COVID-19, remain unclear.

Methods: This was a retrospective cohort study using electronic medical record data. From May 30, 2023, to October 8, 2023, 115 patients with moderate to severe COVID-19 were retrospectively collected from Wenzhou Central Hospital. They were treated with simnotrelvir/ritonavir or nirmatrelvir/ritonavir. The clinical effectiveness and adverse reactions were analyzed and compared between the two groups.

Results: A total of 115 hospitalized patients were included in the study. They were 65 (56.5%) men and 50 (43.5%) women, with a mean age of 61 years. 58 (50.4%) were treated with simnotrelvir/ritonavir and 57 (49.6%) with nirmatrelvir/ritonavir. There was a similar rate of composite disease progression (10.3% vs. 7.0%, χ² = 0.401, p = 0.527) and mortality (5.2% vs. 3.5%, χ² = 0.191, p = 0.662) between the two groups. The progression rate from moderate COVID-19 to severe COVID-19 was not significantly different between the two groups (4.5% vs. 6.4%, χ² = 0.148, p = 0.701). Median time for hospitalization was 7.0 (6.0, 8.0) days and 9.0 (8.0, 10.0) days (p = 0.338), and time for SARS-CoV-2 negative conversion was 6.0 (6.0, 7.0) days and 7.0 (6.0, 7.0) days (p = 0.934) in the simnotrelvir/ritonavir group and nirmatrelvir/ritonavir group, respectively. Among moderate patients, time for hospitalization was shorter in the simnotrelvir/ritonavir group [6.0 (6.0, 7.0) vs. 8.0 (8.0, 10.0) days, log-rank p = 0.004, HR = 1.838 (95% CI 1.199-2.815)]. And 5 (8.6%) had adverse drug reactions (ADRs) in the simnotrelvir/ritonavir group and 6 (10.5%) had ADRs in the nirmatrelvir/ritonavir group.

Conclusion: This is the first study comparing the effectiveness of simnotrelvir/ritonavir and nirmatrelvir/ritonavir in moderate and severe COVID-19 patients. Patients who received simnotrelvir/ritonavir exhibited shorter hospitalization. Disease progression, viral clearance times, and symptom resolution time were similar between the two groups.

Keywords: ADR; COVID‐19; clinical effectiveness; nirmatrelvir/ritonavir; simnotrelvir/ritonavir; small‐molecule antiviral drugs.