J Korean Med Sci.  2024 Feb;39(6):e52. 10.3346/jkms.2024.39.e52.

Determining and Comparing the RealWorld Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in Patients Hospitalized With COVID-19

  • 1Division of Infectious Diseases, Department of Internal Medicine, Incheon Medical Center, Incheon, Korea
  • 2Division of Metabolism and Endocrinology, Department of Internal Medicine, Incheon Medical Center, Incheon, Korea


Current guidelines recommend using nirmatrelvir-ritonavir for coronavirus disease 2019 (COVID-19) treatment, but its potential drug interactions and contraindications limit its applicability in certain categories of patients. The aim of the study was to evaluate the real-world effectiveness of molnupiravir and nirmatrelvir-ritonavir in managing COVID-19 among hospitalized patients.
We conducted a retrospective cohort study among hospitalized COVID-19 patients who received molnupiravir or nirmatrelvir-ritonavir and did not require baseline supplemental oxygen from February 2022 to January 2023. We compared the effectiveness of molnupiravir and nirmatrelvir-ritonavir with a focus on disease progression.
The study included 401 high-risk, hospitalized adult COVID-19 patients who received molnupiravir or nirmatrelvir-ritonavir. No significant difference was found in disease progression, the composite outcome of disease progression (4.0% vs. 1.4%, P = 0.782), and O2 supplementation via nasal prong (21.8% vs. 14.8%, P = 0.115) between the patients treated with molnupiravir and those treated with nirmatrelvir-ritonavir. This finding was similar after 1:1 propensity-score matching. In the multivariate analysis, molnupiravir treatment was not significantly associated with progression to severe disease.
In conclusion, our findings suggest that similar to nirmatrelvir-ritonavir, molnupiravir has a distinct potential role in COVID-19 treatment, transcending its current perceived status as only a secondary option.


Molnupiravir; Nirmatrelvir; COVID-19; COVID-19 Drug Treatment


  • Fig. 1 Cumulative incidence of disease progression: the figure displays cumulative incidence plots for progression to severe disease within 21 days in the total cohort (A) and the propensity score-matched cohort (B). No statistically significant differences were identified in either group.


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