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Cited by 269COVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 ResearchRespiratory viral infections research

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

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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 Infectious Diseases
DOI 10.1016/s1473-3099(22)00507-2PMC PMC9401976

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Abstract

Background Data on the effectiveness of oral antivirals in patients with mild-to-moderate COVID-19 are urgently needed. This retrospective cohort study aimed to evaluate the clinical and virological outcomes associated with molnupiravir or nirmatrelvir-ritonavir use in hospitalised patients with mild-to-moderate COVID-19 during a pandemic wave dominated by the omicron BA.2 subvariant. Methods We analysed data from a territory-wide retrospective cohort of patients in Hong Kong who were hospitalised with a confirmed diagnosis of SARS-CoV-2 infection between Feb 26 and April 26, 2022. Data were extracted from the Hospital Authority, the Department of Health, and the Hong Kong Death Registry. Patients were eligible for inclusion if their admission date was within 3 days before or after confirmation of their COVID-19 diagnosis. Those who were admitted to hospital more than 5 days after symptom onset, were younger than 18 years, had a history of oral antiviral use before admission, required supplemental oxygen on admission, had drug-related contraindications to nirmatrelvir-ritonavir use, or had severe renal or severe liver impairment were excluded. Patients who received the oral antivirals molnupiravir or nirmatrelvir-ritonavir were matched with controls using propensity-score matching in a ratio of 1:1. The primary outcome was all-cause mortality and secondary outcomes included a composite outcome of disease progression (all-cause mortality, initiation of invasive mechanical ventilation [IMV], intensive care unit [ICU] admission, or the need for oxygen therapy) and each of these individual disease progression outcomes, and time to reaching a low viral burden (RT-PCR cycle threshold value ≥30). For each event outcome, crude incidence rates were calculated and hazard ratios (HRs) estimated using Cox regression models. Findings We identified 40 776 patients hospitalised with SARS-CoV-2 infection during the study period, with a mean follow-up of 41·3 days (total 925 713 person-days). After exclusions and propensity-score matching, we included 1856 molnupiravir recipients and 1856 matched controls, and 890 nirmatrelvir-ritonavir recipients and 890 matched controls. A lower risk of all-cause mortality was observed in molnupiravir recipients (crude incidence rate per 10 000 person-days 19·98 events [95% CI 16·91-23·45]) versus matched controls (38·07 events [33·85-42·67]; HR 0·48 [95% CI 0·40-0·59], p<0·0001) and in nirmatrelvir-ritonavir recipients (10·28 events [7·03-14·51]) versus matched controls (26·47 events [21·34-32·46]; HR 0·34 [0·23-0·50], p<0·0001). Oral antiviral recipients also had lower risks of the composite disease progression outcome (molnupiravir HR 0·60 [95% CI 0·52-0·69], p<0·0001; nirmatrelvir-ritonavir 0·57 [0·45-0·72], p<0·0001) and need for oxygen therapy (molnupiravir 0·69 [0·57-0·83], p=0·0001; nirmatrelvir-ritonavir 0·73 [0·54-0·97], p=0·032) compared with controls. Time to achieving a low viral burden was significantly shorter among oral antiviral recipients than matched controls (molnupiravir HR 1·38 [95% CI 1·15-1·64], p=0·0005; nirmatrelvir-ritonavir 1·38 [1·07-1·79], p=0·013). Significant differences in initiation of IMV and ICU admission were not found. Interpretation During a wave of SARS-CoV-2 omicron BA.2, initiation of novel oral antiviral treatments in hospitalised patients not requiring oxygen therapy on admission showed substantial clinical benefit. Our findings support the early use of oral antivirals in this population of patients. Funding Health and Medical Research Fund (Health Bureau, Government of the Hong Kong Special Administrative Region). Translation For the Chinese translation of the abstract see Supplementary Materials section.

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  1. [44]44. University of Oxford PANORAMIC: platform adaptive trial of novel antivirals for early treatment of COVID-19 in the community. https://www.panoramictrial.org/

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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
  • Hong Kong Science and Technology Parks Corporation (HK)
  • University of Hong Kong (HK)
Corresponding author
  • Wong, Carlos K H
  • Cowling, Benjamin J
ORCID
Venue
The Lancet Infectious Diseases
Publisher
Elsevier BV
Published
2022-12
Volume
22
Issue
12
Pages
1681-1693
ISSN
1473-3099 (ISSN-L)
DOI
10.1016/s1473-3099(22)00507-2
PMC
PMC9401976
OpenAlex
W4293280590
Cited by
269
References
36
Citations by year
2026: 11 · 2025: 31 · 2024: 65 · 2023: 111 · 2022: 50
FWCI
31.41
Type
journal article
Language
en
Update notices
erratum (2024-02-01)
Open access
Licence
Locations
  • The Lancet Infectious Diseases (publishedVersion)
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
  • Health and Medical Research Fund (COVID190210)
  • Food and Health Bureau
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
COVID-19 pandemic, SARS-CoV-2, molnupiravir, nirmatrelvir/ritonavir, oral antivirals, Omicron BA.2, hospitalized patients, mild to moderate COVID-19, all-cause mortality, disease progression, mechanical ventilation, intensive care unit admission, oxygen therapy, viral load
MeSH terms
SARS-CoV-2, COVID-19 Testing, COVID-19 Drug Treatment, Antiviral Agents, Cytidine, Hong Kong, Humans, Hydroxylamines, Oxygen, Retrospective Studies, Disease Progression, Ritonavir

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