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Clinical Trial
. 2023 Apr;176(4):505-514.
doi: 10.7326/M22-3057. Epub 2023 Mar 14.

Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in Hospitalized Patients With COVID-19 : A Target Trial Emulation Study

Eric Yuk Fai Wan  1 , Vincent Ka Chun Yan  2 , Anna Hoi Ying Mok  3 , Boyuan Wang  3 , Wanchun Xu  3 , Franco Wing Tak Cheng  2 , Francisco Tsz Tsun Lai  4 , Celine Sze Ling Chui  5 , Xue Li  6 , Carlos King Ho Wong  1 , Philip Hei Li  7 , Benjamin John Cowling  8 , Ivan Fan Ngai Hung  7 , Chak Sing Lau  7 , Ian Chi Kei Wong  9 , Esther Wai Yin Chan  10
Affiliations
Clinical Trial

Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in Hospitalized Patients With COVID-19 : A Target Trial Emulation Study

Eric Yuk Fai Wan et al. Ann Intern Med. 2023 Apr.

Abstract

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 nirmatrelvir-ritonavir 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.

Primary funding source: Health and Medical Research Fund Research on COVID-19, Government of the Hong Kong Special Administrative Region; Research Grants Council, Collaborative Research Fund; and Health Bureau, Government of the Hong Kong Special Administrative Region.

PubMed Disclaimer

Conflict of interest statement

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-3057.

Figures

Visual Abstract.
Visual Abstract.. Effectiveness of Molnupiravir and Nirmatrelvir–Ritonavir.
Using electronic databases during the Omicron wave of COVID-19 in Hong Kong, the authors performed a target trial emulation study of the effect of molnupiravir and nirmatrelvir–ritonavir on all-cause mortality, intensive care unit admissions, and use of ventilatory support in hospitalized patients with COVID-19.
Figure 1.
Figure 1.. Study flow diagram.
Identification of molnupiravir and nirmatrelvir–ritonavir users with different vaccination status. ICU = intensive care unit.
Figure 2.
Figure 2.. 28-day cumulative incidence of outcomes.
ICU = intensive care unit; RD = risk difference.
See this image and copyright information in PMC

Comment in

References

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