Effectiveness of Molnupiravir and Nirmatrelvir–Ritonavir in Hospitalized Patients With COVID-19
Eric Yuk Fai Wan, Vincent Ka Chun Yan, Anna Hoi Ying Mok, MPH Boyuan Wang, MPhil Wanchun Xu, Franco Wing Tak Cheng, Francisco Tsz Tsun Lai, Celine Sze Ling Chui, PhD Xue Li, Carlos King Ho Wong, Philip Hei Li, Benjamin John Cowling, Ivan Fan Ngai Hung, Chak Sing Lau, Ian Chi Kei Wong, Esther Wai Yin Chan
Annals of Internal Medicine, doi:10.7326/m22-3057
Background: Whether hospitalized patients benefit from COVID-19 oral antivirals is uncertain. Objective: To examine the real-world effectiveness of molnupiravir and nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the Omicron outbreak. Design: Target trial emulation study. Setting: Electronic health databases in Hong Kong.
Participants: The molnupiravir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 26 February and 18 July 2022 (n = 16 495). The nirmatrelvirritonavir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 16 March and 18 July 2022 (n = 7119). Intervention: Initiation of molnupiravir or nirmatrelvir-ritonavir within 5 days of hospitalization with COVID-19 versus no initiation of molnupiravir or nirmatrelvir-ritonavir. Measurements: Effectiveness against all-cause mortality, intensive care unit (ICU) admission, or use of ventilatory support within 28 days.
Results: The use of oral antivirals in hospitalized patients with COVID-19 was associated with a lower risk for all-cause mortality (molnupiravir: hazard ratio [HR], 0.87 [95% CI, 0.81 to 0.93]; nirmatrelvir-ritonavir: HR, 0.77 [CI, 0.66 to 0.90]) but no significant risk reduction in terms of ICU admission (molnupiravir: HR, 1.02 [CI, 0.76 to 1.36]; nirmatrelvir-ritonavir: HR, 1.08 [CI, 0.58 to 2.02]) or the need for ventilatory support (molnupiravir: HR, 1.07 [CI, 0.89 to 1.30]; nirmatrelvir-ritonavir: HR, 1.03 [CI, 0.70 to 1.52]). There was no significant interaction between drug treatment and the number of COVID-19 vaccine doses received, thereby supporting the effectiveness of oral antivirals regardless of vaccination status. No significant interaction between nirmatrelvir-ritonavir treatment and age, sex, or Charlson Comorbidity Index was observed, whereas molnupiravir tended to be more effective in older people.
Limitation: The outcome of ICU admission or need for ventilatory support may not capture all severe COVID-19 cases; unmeasured confounders, such as obesity and health behaviors, may exist.
Conclusion: Molnupiravir and nirmatrelvir-ritonavir reduced all-cause mortality in both vaccinated and unvaccinated hospitalized patients. No significant reduction in ICU admission or the need for ventilatory support was observed.
Disclaimer: The corresponding authors had full access to all of the data in the study and take final responsibility for the decision to submit it for publication.
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