Effectiveness comparison of nirmatrelvir/ritonavir versus molnupiravir in COVID-19 patients with comorbidities in Taiwan: a multi-centre electronic health record study

Wen-Kuang Lin; Shwu-Jiuan Lin; Yu-Hui Chang; Fu-Der Wang; Phung-Anh Nguyen; Phan Thanh Phuc; Whitney Burton; Nguyen Thi Kim Hien; Chia-Chieh Lin; Carlos Shu-Kei Lam; To-Chi Ha; Christine Y Lu; Chih-Wei Huang; Hsuan-Chia Yang; Shiue-Ming Lin; Chieh Yang; Li-Hsuan Wang; Jason C Hsu

doi:10.1186/s12879-025-12316-0

Effectiveness comparison of nirmatrelvir/ritonavir versus molnupiravir in COVID-19 patients with comorbidities in Taiwan: a multi-centre electronic health record study

BMC Infect Dis. 2025 Dec 11;26(1):70. doi: 10.1186/s12879-025-12316-0.

Authors

Wen-Kuang Lin¹, Shwu-Jiuan Lin¹, Yu-Hui Chang¹, Fu-Der Wang^{2

3}, Phung-Anh Nguyen^{4

5

6

7}, Phan Thanh Phuc⁸, Whitney Burton⁸, Nguyen Thi Kim Hien^{9

10}, Chia-Chieh Lin¹¹, Carlos Shu-Kei Lam^{12

13}, To-Chi Ha^{14

15}, Christine Y Lu^{16

17

18}, Chih-Wei Huang^{5

19}, Hsuan-Chia Yang^{5

19

20

21}, Shiue-Ming Lin⁶, Chieh Yang⁶, Li-Hsuan Wang^{1

22}, Jason C Hsu^{23

24

25

26}

Affiliations

¹ School of Pharmacy, College of Pharmacy, Taipei Medical University, No.250, Wuxing St., Xinyi Dist., Taipei City, 110, Taiwan (R.O.C.).
² Division of Infection Diseases, Department of Internal Medicine, Taipei Medical University Hospital, No. 252, Wuxing St, Xinyi District, Taipei City, 110, Taiwan (R.O.C.).
³ Institute of Public Health, National Yang-Ming Chiao-Tung University, No. 155, Sec. 2, Linong St., Beitou Dist., Taipei City, 112304, Taiwan (R.O.C.).
⁴ Clinical Data Center, Office of Data Science, Taipei Medical University, No.250, Wuxing St., Xinyi Dist., Taipei City, 110, Taiwan (R.O.C.).
⁵ Clinical Big Data Research Center, Taipei Medical University Hospital, Taipei Medical University, No. 252, Wuxing St, Xinyi District, Taipei City, 110, Taiwan (R.O.C.).
⁶ Research Center of Data Science on Healthcare Industry, College of Management, Taipei Medical University, 11 Fl., Biomedical Technology Building, 301 Yuantong Rd., Zhonghe Dist., New Taipei City, 235, Taiwan (R.O.C.).
⁷ Graduate Institute of Data Science, College of Management, Taipei Medical University, 11 Fl., Biomedical Technology Building, 301 Yuantong Rd., Zhonghe Dist., New Taipei City, 235, Taiwan (R.O.C.).
⁸ International Ph.D. Program in Biotech and Healthcare Management, College of Management, Taipei Medical University, 11 Fl., Biomedical Technology Building, 301 Yuantong Rd., Zhonghe Dist., New Taipei City, 235, Taiwan (R.O.C.).
⁹ Master Program in Global Health and Health Security, College of Public Health, Taipei Medical University, No.250, Wuxing St., Xinyi Dist., Taipei City, 110, Taiwan (R.O.C.).
¹⁰ School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, No.250, Wuxing St., Xinyi Dist., Taipei City, 110, Taiwan (R.O.C.).
¹¹ Department of Pharmacy, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Rd., Beitou District, Taipei City, 112, Taiwan (R.O.C.).
¹² Emergency Department, Department of Emergency and Critical Care Medicine, Wan Fang Hospital, Taipei Medical University, No.111, Sec. 3, Xinglong Rd., Wenshan Dist., Taipei City, 116, Taiwan (R.O.C.).
¹³ Department of Emergency, School of Medicine, College of Medicine, Taipei Medical University, No.250, Wuxing St., Xinyi Dist., Taipei City, 110, Taiwan (R.O.C.).
¹⁴ Department of Emergency and Critical Care Medicine, Taipei Medical University Shuang Ho Hospital, No.291, Zhongzheng Rd., Zhonghe District, New Taipei City, 23561, Taiwan (R.O.C.).
¹⁵ Department of Emergency, School of Medicine, Taipei Medical University, No.250, Wuxing St., Xinyi Dist., Taipei City, 110, Taiwan (R.O.C.).
¹⁶ Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, 401 Park Dr, Boston, MA, 02215, USA.
¹⁷ Kolling Institute, Faculty of Medicine and Health, The University of Sydney and the Northern Sydney Local Health District, Reserve Rd, St Leonards, Sydney, NSW, 2065, Australia.
¹⁸ School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, A15, Science Road, Camperdown, Sydney, NSW, 2050, Australia.
¹⁹ International Center for Health Information Technology (ICHIT), Taipei Medical University, No.250, Wuxing St., Xinyi Dist., Taipei City, 110, Taiwan (R.O.C.).
²⁰ Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, No.250, Wuxing St., Xinyi Dist., Taipei City, 110, Taiwan (R.O.C.).
²¹ Research Center of Big Data and Meta-analysis, Wan Fang Hospital, Taipei Medical University, No.111, Sec. 3, Xinglong Rd., Wenshan Dist., Taipei City, 116, Taiwan (R.O.C.).
²² Department of Pharmacy, Taipei Medical University Hospital, No. 252, Wuxing St, Xinyi District, Taipei City, 110, Taiwan (R.O.C.).
²³ Clinical Data Center, Office of Data Science, Taipei Medical University, No.250, Wuxing St., Xinyi Dist., Taipei City, 110, Taiwan (R.O.C.). jasonhsu@tmu.edu.tw.
²⁴ Clinical Big Data Research Center, Taipei Medical University Hospital, Taipei Medical University, No. 252, Wuxing St, Xinyi District, Taipei City, 110, Taiwan (R.O.C.). jasonhsu@tmu.edu.tw.
²⁵ Research Center of Data Science on Healthcare Industry, College of Management, Taipei Medical University, 11 Fl., Biomedical Technology Building, 301 Yuantong Rd., Zhonghe Dist., New Taipei City, 235, Taiwan (R.O.C.). jasonhsu@tmu.edu.tw.
²⁶ International Ph.D. Program in Biotech and Healthcare Management, College of Management, Taipei Medical University, 11 Fl., Biomedical Technology Building, 301 Yuantong Rd., Zhonghe Dist., New Taipei City, 235, Taiwan (R.O.C.). jasonhsu@tmu.edu.tw.

Abstract

Background: COVID-19 patients frequently present with various comorbidities. Two developed antiviral medications, nirmatrelvir/ritonavir and molnupiravir, have been utilized in COVID-19 patients; but comparisons of the effectiveness between nirmatrelvir/ritonavir and molnupiravir in COVID-19 patients with different comorbidities remain unknown. This study aims to compare the effectiveness, including invasive ventilation and mortality, of nirmatrelvir/ritonavir and molnupiravir in the overall population and populations with various comorbidities in Taiwanese patients during the omicron BA.2 wave.

Methods: We retrospectively collected electronic medical records from the Taipei Medical University Clinical Research Database between January and December 2022 and conducted an analysis of adult patients diagnosed with SARS-CoV-2 infection. For data management, we performed propensity score matching to minimize the imbalance between two groups; the standardized mean difference > 0.1 or a p value < 0.05 considered statistically significant. Variables, which remained imbalanced after matching, were adjusted by cox regression model. To identify the risk associated with these variables, a Cox proportional hazards model were performed. Kaplan-Meier method was applied to estimate invasive ventilation and mortality, comparing survival curves between nirmatrelvir/ritonavir users and molnupiravir users.

Results: Our cohort was recruited from a database, including patients who receive nirmatrelvir/ritonavir or molnupiravir treatment. Out of a total of 35,617 patients, 968 patients received nirmatrelvir/ritonavir and 1198 patients received molnupiravir after matching. Patients with chronic liver disease or mental disease on nirmatrelvir/ritonavir had lower risks of intubation than those on molnupiravir. Overall, nirmatrelvir/ritonavir reduced mortality risk by 65% (adjusted hazard ratio (aHR): 0.35, 95% confidence interval (CI): 0.14-0.88, p = 0.026). For patients with diabetes mellitus (aHR: 0.29, 95% CI: 0.11-0.78, p = 0.014), with chronic kidney disease (aHR: 0.26, 95% CI: 0.10-0.68, p = 0.007), or aged over 65 years (aHR: 0.30, 95% CI: 0.13-0.70, p = 0.005), nirmatrelvir/ritonavir demonstrated superior efficacy in reducing mortality risk compared to molnupiravir.

Conclusions: Data revealed that both nirmatrelvir/ritonavir and molnupiravir demonstrated clinical benefits in treating COVID-19 patients in a real-world setting. Moreover, nirmatrelvir/ritonavir was associated with a lower risk of mortality in COVID-19 patients with specific circumstances.

Clinical trial: Clinical trial number is not applicable.

Keywords: COVID-19; Comorbidity; Molnupiravir; Nirmatrelvir/ritonavir; Taipei medical university clinical research database (TMUCRD); Taiwan.

Publication types

Comparative Study
Multicenter Study

MeSH terms

Adult
Aged
Antiviral Agents* / therapeutic use
COVID-19 Drug Treatment*
COVID-19* / epidemiology
COVID-19* / mortality
Comorbidity
Cytidine* / analogs & derivatives
Cytidine* / therapeutic use
Electronic Health Records
Female
Humans
Hydroxylamines* / therapeutic use
Imines
Male
Middle Aged
Morpholines* / therapeutic use
Proline* / analogs & derivatives
Proline* / therapeutic use
Retrospective Studies
Ritonavir* / therapeutic use
SARS-CoV-2 / drug effects
Taiwan / epidemiology
Treatment Outcome

Substances

Ritonavir
Antiviral Agents
molnupiravir
Hydroxylamines
Cytidine
Proline
Morpholines
Imines

Abstract

Publication types

MeSH terms

Substances

Grants and funding