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

## TL;DR

This study compares the effectiveness of two antiviral drugs, nirmatrelvir/ritonavir and molnupiravir, in treating COVID-19 patients with comorbidities in Taiwan, finding that nirmatrelvir/ritonavir reduces mortality risk more effectively.

## Contribution

The study provides real-world evidence comparing the effectiveness of two antiviral drugs in patients with comorbidities during the omicron BA.2 wave.

## Key findings

- Nirmatrelvir/ritonavir reduced mortality risk by 65% compared to molnupiravir in the overall population.
- Patients with diabetes, chronic kidney disease, or over 65 years had significantly lower mortality risk with nirmatrelvir/ritonavir.
- Nirmatrelvir/ritonavir was associated with lower intubation risk in patients with chronic liver disease or mental disease.

## Abstract

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.

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.

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.

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 number is not applicable.

The online version contains supplementary material available at 10.1186/s12879-025-12316-0.