BACKGROUND: We examined the clinical effectiveness of molnupiravir in reducing deaths in a real-world cohort of adult patients with COVID-19 during the Omicron outbreak. METHODS: This was a population-wide retrospective cohort study in the Czech Republic. We analyzed all 74 541 patients with an officially registered diagnosis of SARS-CoV-2 infection between 1 January and 31 December 2022, aged 18 years or older, treated with molnupiravir. The primary outcome was 30-day all-cause mortality; the secondary outcome was 30-day COVID-19-related mortality. Hazard ratios (HRs) were estimated using stratified Cox regression and the Fine-Gray model. RESULTS: The use of molnupiravir in adult SARS-CoV-2 positive patients was associated with a lower risk of both 30-day all-cause mortality: adjusted HR 0.58 (95% confidence interval, 0.53-0.64; P < .001) and 30-day COVID-19-related mortality: adjusted HR 0.50 (95% confidence interval, 0.42-0.58; P < .001). The effect of molnupiravir was highly significant regardless of sex, Deyo-Charlson Comorbidity Index score, hospitalization status, COVID-19 vaccination status, and patients older than age 65 years. CONCLUSIONS: In this cohort study, early initiation of molnupiravir was associated with a significant reduction in 30-day all-cause and COVID-19-related mortality in adult SARS-CoV-2 positive patients.

Department of Anaesthesia and Intensive Care Medicine Charles University Prague 3rd Faculty of Medicine Prague Czech Republic

Department of Anesthesiology Resuscitation and Intensive Medicine Charles University Prague Faculty of Medicine in Hradec Králové Hradec Králové Czech Republic

Department of Data Analysis Institute of Health Information and Statistics of the Czech Republic Prague Czech Republic

Department of Infectious Diseases Masaryk Hospital in Ústí and Labem Ústí and Labem Czech Republic

Department of Paediatric Anaesthesiology and Intensive Care Medicine University Hospital Brno and Medical Faculty of Masaryk University Brno Czech Republic

Department of Radiology and Nuclear Medicine University Hospital Brno and Medical Faculty of Masaryk University Prague Czech Republic

Department of Respiratory Medicine 1st Faculty of Medicine Charles University and Thomayer University Hospital Prague Czech Republic

Department of Simulation Medicine Faculty of Medicine Masaryk University Brno Czech Republic

Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University Brno Czech Republic

Minister of Health Ministry of Health of the Czech Republic Prague Czech Republic

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Polack  FP, Thomas  SJ, Kitchin  N, et al.  Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med  2020; 383:2603–15. PubMed PMC

Sadoff  J, Gray  G, Vandebosch  A, et al.  Safety and efficacy of single-dose Ad26.COV2.S vaccine against COVID-19. N Engl J Med  2021; 384:2187–201. PubMed PMC

Šmíd  M, Berec  L, Přibylová  L, et al.  Protection by vaccines and previous infection against the omicron variant of severe acute respiratory syndrome coronavirus 2. J Infect Dis  2022; 226:1385–90.Erratum in: J Infect Dis. 2023 Apr 18;227(8):1021–1022. PMID: 35482442; PMCID: PMC9129207. PubMed PMC

Jayk Bernal  A, Gomes da Silva  MM, Musungaie  DB, et al.  Molnupiravir for oral treatment of COVID-19 in nonhospitalized patients. N Engl J Med  2022; 386:509–20. PubMed PMC

Hammond  J, Leister-Tebbe  H, Gardner  A, et al.  Oral nirmatrelvir for high-risk, nonhospitalized adults with COVID-19. N Engl J Med  2022; 386:1397–408. PubMed PMC

Wen  W, Chen  C, Tang  J, et al.  Efficacy and safety of three new oral antiviral treatment (molnupiravir, fluvoxamine and Paxlovid) for COVID-19: a meta-analysis. Ann Med  2022; 54:516–23. PubMed PMC

Wong  CKH, Au  ICH, Lau  KTK, 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: an observational study. Lancet  2022; 400:1213–22. PubMed PMC

Xie  Y, Bowe  B, Al-Aly  Z. Molnupiravir and risk of hospital admission or death in adults with COVID-19: emulation of a randomized target trial using electronic health records. BMJ  2023; 380:e072705. PubMed PMC

Wan  EYF, Yan  VKC, Mok  AHY, et al.  Effectiveness of molnupiravir and nirmatrelvir-ritonavir in hospitalized patients with COVID-19: a target trial emulation study. Ann Intern Med  2023; 176:505–14. PubMed PMC

Lin  DY, Abi Fadel  F, Huang  S, et al.  Nirmatrelvir or molnupiravir use and severe outcomes from omicron infections. JAMA Netw Open  2023; 6:e2335077. PubMed PMC

Butler  CC, Hobbs  FDR, Gbinigie  OA, et al.  Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet  2023; 401:281–93. PubMed PMC

Habibzadeh  F. Disparity in the selection of patients in clinical trials. Lancet  2022; 399:1048. PubMed

Evans  A, Qi  C, Adebayo  JO, et al.  Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: a retrospective cohort study. J Infect  2023; 86:352–60. PubMed PMC

Wong  CKH, Au  ICH, Lau  KTK, et al.  Real-world effectiveness of early molnupiravir or nirmatrelvir-ritonavir in hospitalised patients with COVID-19 without supplemental oxygen requirement on admission during Hong Kong's omicron BA.2 wave: a retrospective cohort study. Lancet Infect Dis  2022; 22:1681–93. PubMed PMC

Najjar-Debbiny  R, Gronich  N, Weber  G, et al.  Effectiveness of molnupiravir in high-risk patients: a propensity score matched analysis. Clin Infect Dis  2023;76:453–60. PubMed

WHO . Therapeutics and COVID-19: living guideline. Geneva: World Health Organization, 2022. PubMed

European Medicines Agency. Summary of product characteristics. Paxlovid. 2022. Available at: https://www.ema.europa.eu/en/documents/product-information/paxlovid-epar-product-information_en.pdf [Accessed 23 June 2023].

Mathis  A, Rooks  R. Geographic differences in vaccine hesitancy among older adults. Public Policy Aging Rep  2022; 32(4):146–148. PubMed PMC

Zhang  D, Zhou  W, Poon  PK, et al.  Vaccine resistance and hesitancy among older adults who live alone or only with an older partner in community in the early stage of the fifth wave of COVID-19 in Hong Kong. Vaccines (Basel)  2022; 10:1118. PubMed PMC

gisaid.org/hcov19-variants [Internet]. GISAID hCoV-19 Variants Dashboard; c2008 [cited 2023 Jun 23]. Available at: https://gisaid.org/hcov-19-variants-dashboard/.

Shu  Y, McCauley  J. GISAID: global initiative on sharing all influenza data - from vision to reality. Euro Surveill  2017; 22:30494. PubMed PMC

Information System of Infectious Diseases. Prague: Institute of Health Information and Statistics of the Czech Republic; c2018 [updated 2023 Mar 31; cited 2023 Jun 23]. Available at: https://www.uzis.cz/isin.

Berec  L, Šmíd  M, Přibylová  L, et al.  Protection provided by vaccination, booster doses and previous infection against COVID-19 infection, hospitalisation or death over time in Czechia. PLoS One  2022; 17:e0270801.Erratum in: PLoS One. 2023 Nov 28;18(11):e0295159. PMID: 35802590; PMCID: PMC9269461. PubMed PMC

Death Certificate System [Internet]. Prague: Czech Statistical Office; c1999 [updated 2001 Nov 20; cited 2023 Jun 23]. Available at: https://www.uzis.cz/lpz.

National Registry of Reimbursed Health Services [Internet]. Prague: Institute of Health Information and Statistics of the Czech Republic; c2016 [updated 2023 Mar 31; cited 2023 Jun 23]. Available at: https://www.uzis.cz/nrhzs.

Rozhodnutí o dočasném povolení distribuce, výdeje a používání léčivého přípravku LAGEVRIO. Ministry of Health of the Czech Republic, Č. j.: MZDR 41627/2021-3/OLZP (Dec. 7, 2021). Available at: https://www.mzcr.cz/rozhodnuti-o-docasnem-povoleni-distribuce-vydeje-a-pouzivani-leciveho-pripravku-lagevrio/.

Wang  C, Liu  B, Zhang  S, et al.  Differences in incidence and fatality of COVID-19 by SARS-CoV-2 omicron variant versus Delta variant in relation to vaccine coverage: a world-wide review. J Med Virol  2023; 95:e28118. PubMed PMC

Wai  AK, Chan  CY, Cheung  AW, et al.  Association of molnupiravir and nirmatrelvir-ritonavir with preventable mortality, hospital admissions and related avoidable healthcare system cost among high-risk patients with mild to moderate COVID-19. Lancet Reg Health West Pac  2023;30:100602. PubMed PMC

Wai  AK, Lee  TT, Chan  SC, et al.  Association of molnupiravir and nirmatrelvir-ritonavir with reduced mortality and sepsis in hospitalized omicron patients: a territory-wide study. Sci Rep  2023; 13:7832. PubMed PMC

Lui  DTW, Chung  MSH, Lau  EHY, et al.  Analysis of all-cause hospitalization and death among nonhospitalized patients with type 2 diabetes and SARS-CoV-2 infection treated with molnupiravir or nirmatrelvir-ritonavir during the omicron wave in Hong Kong. JAMA Netw Open  2023; 6:e2314393. PubMed PMC

OECD/European Observatory on Health Systems and Policies, Czech Republic: Country Health Profile 2021, State of Health in the EU, OECD Publishing, Paris, 2021. Available at: 10.1787/8b341a5e-en. DOI

Zhang  T, Nishiura  H. Estimating infection fatality risk and ascertainment bias of COVID-19 in Osaka, Japan from February 2020 to January 2022. Sci Rep  2023; 13:5540. PubMed PMC

Dorabawila  V, Barnes  V, Ramesh  N, et al.  Comparison of COVID-19 home-testers vs. Laboratory-testers in New York state (excluding New York city), November 2021 to April 2022. Front Public Health  2023; 11:1058644. PubMed PMC

Rader  B, Gertz  A, Iuliano  AD, et al.  Use of at-home COVID-19 tests - United States, August 23, 2021-march 12, 2022. MMWR Morb Mortal Wkly Rep  2022; 71:489–94. PubMed PMC