Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2025 Jul 1;25(1):840.
doi: 10.1186/s12879-025-11195-9.

Real-world effectiveness of simnotrelvir-ritonavir versus nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the omicron wave in China: a retrospective cohort study

Chuntao Li #  1 , Qingzhao Cheng #  1 , Ying Chen  2 , Ling Liu  1 , Dajin Liu  3 , Jiaqiang Zhang  1 , Zehua Liao  1 , Yaling Xiang  1 , Jinbiao Zhou  1 , Keke Liao  1 , Yandi Su  1 , Xuemei Zhang  1 , Jiashu Li  1 , Yuping Zhao  1 , Yue Yang  1 , Jianqing Zhang  4 , Long Yang  5
Affiliations
Comparative Study

Real-world effectiveness of simnotrelvir-ritonavir versus nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the omicron wave in China: a retrospective cohort study

Chuntao Li et al. BMC Infect Dis. .

Abstract

Objective: 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.

Methods: 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.

Results: 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 < 0.05). The multivariate Cox regression analysis revealed that non-severe COVID-19 (HR 0.630, 95% CI 0.496-0.801; p < 0.001), lower C-reactive protein (CRP) levels (HR 0.993, 95% CI 0.990-0.997; p < 0.001), and treatment with simnotrelvir-ritonavir (HR 1.395, 95% CI 1.118-1.741; p = 0.003) were independently associated with a higher likelihood of clinical improvement.

Conclusion: This study illustrated that both simnotrelvir-ritonavir and nirmatrelvir-ritonavir exhibited similar effectiveness in reducing the incidence of composite disease progression, all-cause death, and the need for respiratory support amidst the real-world outbreak of the omicron VOC in China. Furthermore, simnotrelvir-ritonavir was found to be more favorable in enhancing the rate of clinical improvement in COVID-19 hospitalized patients, suggesting its potential clinical effectiveness against the disease.

Keywords: All-cause death; COVID‐19; Clinical improvement; Composite disease progression; Nirmatrelvir-ritonavir; Simnotrelvir-ritonavir.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. Verbal informed consent was obtained from all participants in this study through telephone follow-up procedures. Approval of Clinical Research by the Ethics Committee of the First Affiliated Hospital of Kunming Medical University[(2024 L)No. 75]. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Identification of simnotrelvir-ritonavir recipients and nirmatrelvir-ritonavir recipients among COVID‐19 hospitalized patients
Fig. 2
Fig. 2
Cumulative incidence of composite and individual outcomes for simnotrelvir-ritonavir vs nirmatrelvir-ritonavir group. A composite disease progression outcome, B all‐cause death, C invasive mechanical ventilation, D noninvasive mechanical ventilation, E high‐flow oxygen therapy, F Clinical improvement
Fig. 3
Fig. 3
The effectiveness of clinical improvement for simnotrelvir-ritonavir vs nirmatrelvir-ritonavir group. Note: CI, confidence interval. HR, hazard ratio. (-) Indicates that the model cannot be fitted because the 95%CI is too large or because a subgroup is not available for analysis
See this image and copyright information in PMC

References

    1. World Health Organization (WHO). Number of COVID-19 cases reported to WHO. 2024. Available from: https://data.who.int/dashboards/covid19/cases?n=c. Cited 2025 May 3.
    1. Centers for Disease Control and Prevention (CDC). SARS-CoV-2 variant classifications anddefinitions. 2023. Available from: https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-classificatio.... Cited 2025 May 3.
    1. Global Initiative on Sharing All Influenza Data (GISAID). Phylodynamics of pandemic coronavirus across the globe. 2024. Available from: https://gisaid.org/phylodynamics/global/nextstrain. Cited 2025 May 3.
    1. Chinese Center for Disease Control and Prevention (China CDC). COVID-19 vaccination status. 2022. Available from: https://www.chinacdc.cn/jkzt/crb/zl/szkb_11803/jszl_12208/202212/t202212.... Cited 2025 May 3.
    1. World Health Organization (WHO). Therapeutics and COVID-19: living guideline. 2023. Available from: https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2023.2. Cited 2025 May 3. - PubMed

Publication types

MeSH terms

LinkOut - more resources