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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. doi: 10.1186/s12879-025-12316-0. Online ahead of print.

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.

PMID:41382264 | DOI:10.1186/s12879-025-12316-0

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