Molnupiravir and nirmatrelvir-ritonavir reduce mortality risk during post-acute COVID-19 phase

Wan et al., Journal of Infection, doi:10.1016/j.jinf.2023.02.029

Feb 2023

Retrospective 30,040 hospitalized patients in Hong Kong, showing lower mortality with paxlovid treatment. Patients with contraindications to paxlovid were not excluded.

Confounding by contraindication. Hoertel et al. find that over 50% of patients that died had a contraindication for the use of Paxlovid Hoertel. Retrospective studies that do not exclude contraindicated patients may significantly overestimate efficacy.

Black box warning. The FDA notes that "severe, life-threatening, and/or fatal adverse reactions due to drug interactions have been reported in patients treated with paxlovid" FDA.

1. FDA, Fact sheet for healthcare providers: emergency use authorization for paxlovid, www.fda.gov/media/155050/download.fda.gov.

2. Hoertel et al., Prevalence of Contraindications to Nirmatrelvir-Ritonavir Among Hospitalized Patients With COVID-19 at Risk for Progression to Severe Disease, JAMA Network Open, doi:10.1001/jamanetworkopen.2022.42140.jamanetwork.com, doi.org.

Important missing comments or errors? Let us know.

Study covers molnupiravir and paxlovid.

risk of death, 28.0% lower, HR 0.72, p < 0.001, treatment 541 of 6,604 (8.2%), control 2,541 of 17,283 (14.7%), adjusted per study, multivariable, Cox proportional hazards.

risk of hospitalization, 24.0% lower, HR 0.76, p < 0.001, treatment 1,772 of 6,604 (26.8%), control 2,541 of 17,283 (14.7%), adjusted per study, multivariable, Cox proportional hazards.

risk of progression, 18.0% lower, HR 0.82, p < 0.001, treatment 1,816 of 6,604 (27.5%), control 2,541 of 17,283 (14.7%), adjusted per study, A&E admission, multivariable, Cox proportional hazards.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Wan et al., 22 Feb 2023, retrospective, China, peer-reviewed, 13 authors, study period 26 February, 2022 - 30 September, 2022. Contact: ewchan@hku.hk, wongick@hku.hk.

This Paper Paxlovid All

Molnupiravir and nirmatrelvir-ritonavir reduce mortality risk during post-acute COVID-19 phase

Eric Yuk Fai Wan, MPH Boyuan Wang, BSc Sukriti Mathur, Cheyenne I Ying Chan, Vincent Ka Chun Yan, Francisco Tsz Tsun Lai, Celine Sze Ling Chui, PhD Xue Li, Carlos King Ho Wong, Chak Philip Hei Li, Chak Sing Lau, Prof Ian Chi Kei Wong, Dr Esther Wai Yin Chan

Journal of Infection, doi:10.1016/j.jinf.2023.02.029

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Ethics approval This study was approved by the Central Institutional Review Board of the Hospital Authority of Hong Kong (CIRB-2021-005-4) and the DH Ethics Committee (LM171/2021). Data sharing Data will not be made available to others because the data custodians have not given permission. Sources of funding

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Wan, Mok, Yan, Wang, Zhang et al., Vaccine effectiveness of BNT162b2 and CoronaVac against SARS-CoV-2 Omicron BA.2 infection, hospitalisation, severe complications, cardiovascular disease and mortality in patients with diabetes mellitus: A case control study, Journal of Infection

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Wong, Au, Lau, Lau, Cowling et al., Real-world effectiveness of molnupiravir and nirmatrelvir plus ritonavir against mortality, hospitalisation, and in-hospital outcomes among community-dwelling, ambulatory patients with confirmed SARS-CoV-2 infection during the omicron wave in Hong Kong: a, Beta-blockers

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Late treatment
is less effective

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