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Cited by 299COVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 ResearchRespiratory viral infections research

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

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Wong, Carlos K H, Au, Ivan C H, Lau, Kristy T K, Lau, Eric H Y, Cowling, Benjamin J, Leung, Gabriel M·2022·The Lancet
DOI 10.1016/s0140-6736(22)01586-0PMC PMC9539539

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Abstract

Background Little is known about the real-world effectiveness of oral antivirals against the SARS-CoV-2 omicron (B.1.1.529) variant. We aimed to assess the clinical effectiveness of two oral antiviral drugs among community-dwelling COVID-19 outpatients in Hong Kong. Methods In this observational study, we used data from the Hong Kong Hospital Authority to identify an unselected, territory-wide cohort of non-hospitalised patients with an officially registered diagnosis of SARS-CoV-2 infection between Feb 26 and June 26, 2022, during the period in which the omicron subvariant BA.2.2 was dominant in Hong Kong. We used a retrospective cohort design as primary analysis, and a case-control design as sensitivity analysis. We identified patients with COVID-19 who received either molnupiravir (800 mg twice daily for 5 days) or nirmatrelvir plus ritonavir (nirmatrelvir 300 mg and ritonavir 100 mg twice daily for 5 days, or nirmatrelvir 150 mg and ritonavir 100 mg if estimated glomerular filtration rate was 30-59 mL/min per 1·73 m 2). Outpatient oral antiviral users were matched with controls using propensity score (1:10) according to age, sex, date of SARS-CoV-2 infection diagnosis, Charlson Comorbidity Index score, and vaccination status. Study outcomes were death, COVID-19-related hospitalisation, and in-hospital disease progression (in-hospital death, invasive mechanical ventilation, or intensive care unit admission). Hazard ratios (HRs) were estimated by Cox regression for the primary analysis, and odds ratios in oral antiviral users compared with non-users by logistic regression for the sensitivity analysis. Findings Among 1 074 856 non-hospitalised patients with COVID-19, 5383 received molnupiravir and 6464 received nirmatrelvir plus ritonavir in the community setting. Patients were followed up for a median of 103 days in the molnupiravir group and 99 days in the nirmatrelvir plus ritonavir group. Compared with nirmatrelvir plus ritonavir users, those on molnupiravir were older (4758 [85·9%] vs 4418 [88.7%] aged >60 years) and less likely to have been fully vaccinated (1850 [33·4%] vs 800 [16·1%]). Molnupiravir use was associated with lower risks of death (HR 0·76 [95% CI 0·61-0·95]) and in-hospital disease progression (0·57 [0·43-0·76]) than non-use was, whereas risk of hospitalisation was similar in both groups (0·98 [0·89-1·06]). Nirmatrelvir plus ritonavir use was associated with lower risks of death (0·34 [0·22-0·52]), hospitalisation (0·76 [0·67-0·86]), and in-hospital disease progression (0·57 [0·38-0·87]) than non-use was. We consistently found reduced risks of mortality and hospitalisation associated with early oral antiviral use among older patients. The findings from the case-control analysis broadly supported those from the primary analysis. Interpretation During Hong Kong's wave of SARS-CoV-2 omicron subvariant BA.2.2, among non-hospitalised patients with COVID-19, early initiation of novel oral antivirals was associated with reduced risks of mortality and in-hospital disease progression. Nirmatrelvir plus ritonavir use was additionally associated with a reduced risk of hospitalisation. Funding Health and Medical Research Fund, Health Bureau, Government of Hong Kong Special Administrative Region, China. Translation For the Chinese translation of the abstract see Supplementary Materials section.

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Authors
Wong, C. K. H., Au, I. C. H., Lau, K. T. K., Lau, E. H. Y., Cowling, B. J., & Leung, G. M.
Affiliations
  • Laboratory of Data Discovery for Health (HK)
  • University of Hong Kong (HK)
Corresponding author
  • Wong, Carlos K H
  • Cowling, Benjamin J
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2022-10
Volume
400
Issue
10359
Pages
1213-1222
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(22)01586-0
PMC
PMC9539539
OpenAlex
W4303423758
Cited by
299
References
26
Citations by year
2026: 20 · 2025: 39 · 2024: 80 · 2023: 135 · 2022: 23
FWCI
33.86
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet (publishedVersion)
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion, cc-by)
  • The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
Funders
  • Food and Health Bureau (COVID190210)
  • Health and Medical Research Fund (COVID190210)
Topics
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
Keywords
Omicron variant, molnupiravir, oral antiviral therapy, real-world effectiveness, hospitalization, mortality, hospitalization outcomes, mechanical ventilation, intensive care unit admission, Hong Kong
MeSH terms
SARS-CoV-2, COVID-19 Drug Treatment, Antiviral Agents, Cytidine, Hong Kong, Hospitalization, Humans, Hydroxylamines, Retrospective Studies, Hospital Mortality, Disease Progression, Ritonavir, Independent Living

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