Effectiveness and Adverse Events of Nirmatrelvir/Ritonavir Versus Molnupiravir for COVID-19 in Outpatient Setting: Multicenter Prospective Observational Study

Abstract

Background: In this study, we aimed to compare the effectiveness and adverse reactions of nirmatrelvir/ritonavir and molnupiravir in high-risk outpatients with coronavirus disease 2019 (COVID-19).Methods: This multicenter prospective observational study evaluated the rate of hospitalization, death, and adverse events within 28 days of oral antiviral agent prescription (molnupiravir, n = 240; nirmatrelvir/ritonavir, n = 240) to 480 nonhospitalized adult patients with COVID-19 from August 2, 2022 to March 31, 2023.Results: Patients receiving molnupiravir had a higher prevalence of comorbidities (85.8% vs. 70.4%;P < 0.001) and a higher Charlson comorbidity index (2.8 1.4 vs. 2.5 1.5; P = 0.009) than those receiving nirmatrelvir/ritonavir.Three patients required hospitalization (nirmatrelvir/ritonavir group, n = 1 [0.4%]; molnupiravir group, n = 2 [0.8%];P = 1.000).Nirmatrelvir/ritonavir was associated with a higher risk of adverse events than molnupiravir (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.27-3.03),especially for patients aged 65 years and older (OR, 3.04; 95% CI, 1.71-5.39).The severity of adverse events in both groups was mild to moderate and improved after discontinuation of medication.In the molnupiravir group, age 65 years (OR, 0.43 95% CI, 0.22-0.86)and appropriate vaccination (OR, 0.37; 95% CI, 0.15-0.91)reduced the occurrence of adverse events. Conclusion:The rates of hospitalization and death were low and not significantly different between high-risk patients who received either nirmatrelvir/ritonavir or molnupiravir.Although adverse events were more frequent with nirmatrelvir/ritonavir than with molnupiravir, none were severe.Nirmatrelvir/ritonavir can be safely used to treat COVID-19, while molnupiravir could be considered as an alternative treatment option for high-risk groups.

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