Efficacy of COVID-19 Oral antivirals in hospitalised oldest-old with high morbidity burden: a target trial emulation study

{ 'indexed': {'date-parts': [[2024, 8, 15]], 'date-time': '2024-08-15T00:19:03Z', 'timestamp': 1723681143148}, 'reference-count': 27, 'publisher': 'Oxford University Press (OUP)', 'issue': '8', 'license': [ { 'start': { 'date-parts': [[2024, 8, 1]], 'date-time': '2024-08-01T00:00:00Z', 'timestamp': 1722470400000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://academic.oup.com/pages/standard-publication-reuse-rights'}], 'funder': [ {'name': 'Health and Medical Research Fund Research on COVID-19'}, {'name': 'Government of the Hong Kong Special Administrative Region'}, {'name': 'Research Grants Council'}, {'name': 'Collaborative Research Fund'}, {'DOI': '10.13039/100022720', 'name': 'Health Bureau', 'doi-asserted-by': 'publisher'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'published-print': {'date-parts': [[2024, 8, 6]]}, 'abstract': '<jats:title>Abstract</jats:title>\n' ' <jats:sec>\n' ' <jats:title>Background</jats:title>\n' ' <jats:p>Molnupiravir and nirmatrelvir-ritonavir are orally administered ' 'pharmacotherapies for mild to moderate COVID-19. However, the effectiveness of these drugs ' 'among very old (≥80\xa0years), hospitalised patients remains unclear, limiting the ' 'risk–benefit assessment of these antivirals in this specific group. This study investigates ' 'the effectiveness of these antivirals in reducing mortality among this group of hospitalised ' 'patients with COVID-19.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Methods</jats:title>\n' ' <jats:p>Using a territory-wide public healthcare database in Hong Kong, a ' 'target trial emulation study was conducted with data from 13 642 eligible participants for ' 'the molnupiravir trial and 9553 for the nirmatrelvir-ritonavir trial. The primary outcome was ' 'all-cause mortality. Immortal time and confounding bias was minimised using ' 'cloning-censoring-weighting approach. Mortality odds ratios were estimated by pooled logistic ' 'regression after adjusting confounding biases by stabilised inverse probability ' 'weights.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>Both molnupiravir (HR: 0.895, 95% CI: 0.826–0.970) and ' 'nirmatrelvir-ritonavir (HR: 0.804, 95% CI: 0.678–0.955) demonstrated moderate mortality risk ' 'reduction among oldest-old hospitalised patients. No significant interaction was observed ' 'between oral antiviral treatment and vaccination status. The 28-day risk of mortality was ' 'lower in initiators than non-initiators for both molnupiravir (risk difference: −1.09%, 95% ' 'CI: −2.29, 0.11) and nirmatrelvir-ritonavir (risk difference: −1.71%, 95% CI: −3.30, −0.16) ' 'trials. The effectiveness of these medications was observed regardless of the patients’ prior ' 'vaccination status.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Conclusions</jats:title>\n' ' <jats:p>Molnupiravir and nirmatrelvir-ritonavir are moderately effective in ' 'reducing mortality risk among hospitalised oldest-old patients with COVID-19, regardless of ' 'their vaccination status.</jats:p>\n' ' </jats:sec>', 'DOI': '10.1093/ageing/afae180', 'type': 'journal-article', 'created': {'date-parts': [[2024, 8, 14]], 'date-time': '2024-08-14T15:26:27Z', 'timestamp': 1723649187000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Efficacy of COVID-19 Oral antivirals in hospitalised oldest-old with high morbidity burden: a ' 'target trial emulation study', 'prefix': '10.1093', 'volume': '53', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-9121-1959', 'authenticated-orcid': False, 'given': 'Francisco Tsz Tsun', 'family': 'Lai', 'sequence': 'first', 'affiliation': [ { 'name': 'Centre for Safe Medication Practice and Research , Department of ' 'Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 ' 'Sassoon Road, Southern District, Hong Kong Special ' 'Administrative Region , China'}, { 'name': 'The University of Hong Kong , Department of Pharmacology and ' 'Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, ' 'Southern District, Hong Kong Special Administrative Region , ' 'China'}, { 'name': 'Department of Family Medicine and Primary Care , School of ' 'Clinical Medicine, Li Ka Shing Faculty of Medicine, , 21 Sassoon ' 'Road, Southern District, Hong Kong Special Administrative Region ' ', China'}, { 'name': 'The University of Hong Kong , School of Clinical Medicine, Li Ka ' 'Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, ' 'Hong Kong Special Administrative Region , China'}, { 'name': 'Laboratory of Data Discovery for Health (D24H) , 19 Science Park ' 'West Avenue, Hong Kong Science Park, Tai Po District, Hong Kong ' 'Special Administrative Region , China'}]}, { 'given': 'Boyuan', 'family': 'Wang', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Family Medicine and Primary Care , School of ' 'Clinical Medicine, Li Ka Shing Faculty of Medicine, , 21 Sassoon ' 'Road, Southern District, Hong Kong Special Administrative Region ' ', China'}, { 'name': 'The University of Hong Kong , School of Clinical Medicine, Li Ka ' 'Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, ' 'Hong Kong Special Administrative Region , China'}]}, { 'given': 'Cuiling', 'family': 'Wei', 'sequence': 'additional', 'affiliation': [ { 'name': 'Centre for Safe Medication Practice and Research , Department of ' 'Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 ' 'Sassoon Road, Southern District, Hong Kong Special ' 'Administrative Region , China'}, { 'name': 'The University of Hong Kong , Department of Pharmacology and ' 'Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, ' 'Southern District, Hong Kong Special Administrative Region , ' 'China'}]}, { 'ORCID': 'http://orcid.org/0000-0003-1513-8726', 'authenticated-orcid': False, 'given': 'Celine Sze Ling', 'family': 'Chui', 'sequence': 'additional', 'affiliation': [ { 'name': 'Laboratory of Data Discovery for Health (D24H) , 19 Science Park ' 'West Avenue, Hong Kong Science Park, Tai Po District, Hong Kong ' 'Special Administrative Region , China'}, { 'name': 'School of Nursing , Li Ka Shing Faculty of Medicine, , 21 ' 'Sassoon Road, Southern District, Hong Kong Special ' 'Administrative Region , China'}, { 'name': 'The University of Hong Kong , Li Ka Shing Faculty of Medicine, , ' '21 Sassoon Road, Southern District, Hong Kong Special ' 'Administrative Region , China'}, { 'name': 'School of Public Health , Li Ka Shing Faculty of Medicine, , 21 ' 'Sassoon Road, Southern District, Hong Kong Special ' 'Administrative Region , China'}, { 'name': 'The University of Hong Kong , Li Ka Shing Faculty of Medicine, , ' '21 Sassoon Road, Southern District, Hong Kong Special ' 'Administrative Region , China'}, { 'name': 'Advanced Data Analytics for Medical Science (ADAMS) Limited , 19 ' 'Science Park West Avenue, Hong Kong Science Park, Tai Po ' 'District, Hong Kong Special Administrative Region , China'}]}, { 'given': 'Xue', 'family': 'Li', 'sequence': 'additional', 'affiliation': [ { 'name': 'Centre for Safe Medication Practice and Research , Department of ' 'Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 ' 'Sassoon Road, Southern District, Hong Kong Special ' 'Administrative Region , China'}, { 'name': 'The University of Hong Kong , Department of Pharmacology and ' 'Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, ' 'Southern District, Hong Kong Special Administrative Region , ' 'China'}, { 'name': 'Laboratory of Data Discovery for Health (D24H) , 19 Science Park ' 'West Avenue, Hong Kong Science Park, Tai Po District, Hong Kong ' 'Special Administrative Region , China'}, { 'name': 'Department of Medicine , School of Clinical Medicine, Li Ka ' 'Shing Faculty of Medicine, , 102 Pok Fu Lam Road, Southern ' 'District, Hong Kong Special Administrative Region , China'}, { 'name': 'The University of Hong Kong , School of Clinical Medicine, Li Ka ' 'Shing Faculty of Medicine, , 102 Pok Fu Lam Road, Southern ' 'District, Hong Kong Special Administrative Region , China'}]}, { 'given': 'Ching Lung', 'family': 'Cheung', 'sequence': 'additional', 'affiliation': [ { 'name': 'Centre for Safe Medication Practice and Research , Department of ' 'Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 ' 'Sassoon Road, Southern District, Hong Kong Special ' 'Administrative Region , China'}, { 'name': 'The University of Hong Kong , Department of Pharmacology and ' 'Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, ' 'Southern District, Hong Kong Special Administrative Region , ' 'China'}, { 'name': 'Laboratory of Data Discovery for Health (D24H) , 19 Science Park ' 'West Avenue, Hong Kong Science Park, Tai Po District, Hong Kong ' 'Special Administrative Region , China'}]}, { 'ORCID': 'http://orcid.org/0000-0001-8242-0014', 'authenticated-orcid': False, 'given': 'Ian Chi Kei', 'family': 'Wong', 'sequence': 'additional', 'affiliation': [ { 'name': 'Centre for Safe Medication Practice and Research , Department of ' 'Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 ' 'Sassoon Road, Southern District, Hong Kong Special ' 'Administrative Region , China'}, { 'name': 'The University of Hong Kong , Department of Pharmacology and ' 'Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, ' 'Southern District, Hong Kong Special Administrative Region , ' 'China'}, { 'name': 'Laboratory of Data Discovery for Health (D24H) , 19 Science Park ' 'West Avenue, Hong Kong Science Park, Tai Po District, Hong Kong ' 'Special Administrative Region , China'}, { 'name': 'Aston Pharmacy School, Aston University , Birmingham, B4 7ET , ' 'United Kingdom'}, { 'name': 'Department of Pharmacy, The University of Hong Kong-Shenzhen ' 'Hospital , 1 Haiyuan First Road, Futian District, Shenzhen , ' 'China'}, { 'name': 'School of Pharmacy, Macau University of Science and Technology , ' 'Avenida Wai Long, Taipa, Macau , China'}]}, { 'given': 'Esther Wai Yin', 'family': 'Chan', 'sequence': 'additional', 'affiliation': [ { 'name': 'Centre for Safe Medication Practice and Research , Department of ' 'Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 ' 'Sassoon Road, Southern District, Hong Kong Special ' 'Administrative Region , China'}, { 'name': 'The University of Hong Kong , Department of Pharmacology and ' 'Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, ' 'Southern District, Hong Kong Special Administrative Region , ' 'China'}, { 'name': 'Laboratory of Data Discovery for Health (D24H) , 19 Science Park ' 'West Avenue, Hong Kong Science Park, Tai Po District, Hong 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'key': '2024081414092700600_ref4', 'doi-asserted-by': 'crossref', 'first-page': '118', 'DOI': '10.1016/j.ejim.2022.05.024', 'article-title': 'Efficacy and safety of molnupiravir for COVID-19 patients', 'volume': '102', 'author': 'Fatima', 'year': '2022', 'journal-title': 'Eur J Intern Med'}, { 'key': '2024081414092700600_ref5', 'article-title': 'Nirmatrelvir–ritonavir for the treatment of COVID-19 patients: a ' 'systematic review and meta-analysis', 'volume': '95', 'author': 'Cheema', 'year': '2023', 'journal-title': 'J Med Virol'}, { 'key': '2024081414092700600_ref6', 'doi-asserted-by': 'crossref', 'first-page': '1397', 'DOI': '10.1056/NEJMoa2118542', 'article-title': 'Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19', 'volume': '386', 'author': 'Hammond', 'year': '2022', 'journal-title': 'N Engl J Med'}, { 'key': '2024081414092700600_ref7', 'doi-asserted-by': 'crossref', 'DOI': '10.1056/EVIDoa2100043', 'article-title': 'Phase 2/3 trial of molnupiravir for treatment of Covid-19 in ' 'nonhospitalized adults', 'volume': '1', 'author': 'Caraco', 'year': '2022', 'journal-title': 'NEJM Evid'}, { 'key': '2024081414092700600_ref8', 'doi-asserted-by': 'crossref', 'DOI': '10.1056/EVIDoa2100044', 'article-title': 'Randomized trial of molnupiravir or placebo in patients hospitalized ' 'with Covid-19', 'volume': '1', 'author': 'Arribas', 'year': '2022', 'journal-title': 'NEJM Evid'}, {'key': '2024081414092700600_ref9', 'volume': '176', 'journal-title': 'Ann Intern Med.'}, { 'key': '2024081414092700600_ref10', 'doi-asserted-by': 'crossref', 'first-page': 'E220', 'DOI': '10.1503/cmaj.221608', 'article-title': 'Population-based evaluation of the effectiveness of ' 'nirmatrelvir–ritonavir for reducing hospital admissions and mortality ' 'from COVID-19', 'volume': '195', 'author': 'Schwartz', 'year': '2023', 'journal-title': 'Cmaj'}, { 'key': '2024081414092700600_ref11', 'doi-asserted-by': 'crossref', 'first-page': '505', 'DOI': '10.7326/M22-3057', 'article-title': 'Effectiveness of Molnupiravir and Nirmatrelvir–ritonavir in ' 'hospitalized patients with COVID-19: a target trial emulation study', 'volume': '176', 'author': 'Wan', 'year': '2023', 'journal-title': 'Ann Intern Med'}, { 'key': '2024081414092700600_ref12', 'doi-asserted-by': 'crossref', 'first-page': '501', 'DOI': '10.1093/ageing/afaa093', 'article-title': 'COVID-19 in older people: a rapid clinical review', 'volume': '49', 'author': 'Lithander', 'year': '2020', 'journal-title': 'Age Ageing'}, { 'key': '2024081414092700600_ref13', 'doi-asserted-by': 'crossref', 'first-page': '6', 'DOI': '10.1046/j.1365-2125.2003.02007.x', 'article-title': 'Age-related changes in pharmacokinetics and pharmacodynamics: basic ' 'principles and practical applications', 'volume': '57', 'author': 'Mangoni', 'year': '2004', 'journal-title': 'Br J Clin Pharmacol'}, { 'key': '2024081414092700600_ref14', 'doi-asserted-by': 'crossref', 'first-page': '1912', 'DOI': '10.1016/j.jacc.2022.08.800', 'article-title': 'Cardiovascular drug interactions with nirmatrelvir/ritonavir in ' 'patients with COVID-19: JACC review topic of the week', 'volume': '80', 'author': 'Abraham', 'year': '2022', 'journal-title': 'J Am Coll Cardiol'}, { 'key': '2024081414092700600_ref15', 'doi-asserted-by': 'crossref', 'first-page': '64', 'DOI': '10.1016/S1473-3099(21)00451-5', 'article-title': "Bell's palsy following vaccination with mRNA (BNT162b2) and inactivated " '(CoronaVac) SARS-CoV-2 vaccines: a case series and nested case-control ' 'study', 'volume': '22', 'author': 'Wan', 'year': '2022', 'journal-title': 'Lancet Infect Dis'}, { 'key': '2024081414092700600_ref16', 'doi-asserted-by': 'crossref', 'first-page': '673', 'DOI': '10.1093/cid/ciab989', 'article-title': 'Epidemiology of acute myocarditis/pericarditis in Hong Kong adolescents ' 'following Comirnaty vaccination', 'volume': '75', 'author': 'Chua', 'year': '2022', 'journal-title': 'Clin Infect Dis'}, { 'key': '2024081414092700600_ref17', 'doi-asserted-by': 'crossref', 'first-page': '564', 'DOI': '10.1136/annrheumdis-2021-221571', 'article-title': 'Two-dose COVID-19 vaccination and possible arthritis flare among ' 'patients with rheumatoid arthritis in Hong Kong', 'volume': '81', 'author': 'Li', 'year': '2022', 'journal-title': 'Ann Rheum Dis'}, { 'key': '2024081414092700600_ref18', 'doi-asserted-by': 'crossref', 'first-page': '411', 'DOI': '10.1038/s41467-022-28068-3', 'article-title': 'Multimorbidity and adverse events of special interest associated with ' 'Covid-19 vaccines in Hong Kong', 'volume': '13', 'author': 'Lai', 'year': '2022', 'journal-title': 'Nat Commun'}, { 'key': '2024081414092700600_ref19', 'doi-asserted-by': 'crossref', 'first-page': '362', 'DOI': '10.7326/M21-3700', 'article-title': 'Carditis after COVID-19 vaccination with a messenger RNA vaccine and an ' 'inactivated virus vaccine: a case–control study', 'volume': '175', 'author': 'Lai', 'year': '2022', 'journal-title': 'Ann Intern Med'}, { 'key': '2024081414092700600_ref20', 'doi-asserted-by': 'crossref', 'first-page': '864', 'DOI': '10.1111/joim.13453', 'article-title': 'Post-Covid-19-vaccination adverse events and healthcare utilization ' 'among individuals with or without previous SARS-CoV-2 infection', 'volume': '291', 'author': 'Lai', 'year': '2022', 'journal-title': 'J Intern Med'}, { 'key': '2024081414092700600_ref21', 'doi-asserted-by': 'crossref', 'first-page': '2608', 'DOI': '10.1136/gutjnl-2021-326860', 'article-title': 'Lack of inflammatory bowel disease flare-up following two-dose BNT162b2 ' 'vaccine: a population-based cohort study', 'volume': '71', 'author': 'Li', 'year': '2022', 'journal-title': 'Gut'}, { 'key': '2024081414092700600_ref22', 'article-title': 'Herpes zoster related hospitalization after inactivated (CoronaVac) and ' 'mRNA (BNT162b2) SARS-CoV-2 vaccination: a self-controlled case series ' 'and nested case-control study', 'volume': '21', 'author': 'Wan', 'year': '2022', 'journal-title': 'Lancet Reg Health West Pac'}, { 'key': '2024081414092700600_ref23', 'doi-asserted-by': 'crossref', 'first-page': '505', 'DOI': '10.1089/thy.2021.0684', 'article-title': 'Safety of inactivated and mRNA COVID-19 vaccination among patients ' 'treated for hypothyroidism: a population-based cohort study', 'volume': '32', 'author': 'Xiong', 'year': '2022', 'journal-title': 'Thyroid'}, {'key': '2024081414092700600_ref24', 'volume': '32', 'journal-title': 'Adv Clin Exp Med'}, { 'key': '2024081414092700600_ref25', 'doi-asserted-by': 'crossref', 'first-page': '1054', 'DOI': '10.1016/S0140-6736(20)30566-3', 'article-title': 'Clinical course and risk factors for mortality of adult inpatients with ' 'COVID-19 in Wuhan, China: a retrospective cohort study', 'volume': '395', 'author': 'Zhou', 'year': '2020', 'journal-title': 'Lancet'}, { 'key': '2024081414092700600_ref26', 'doi-asserted-by': 'crossref', 'first-page': '1', 'DOI': '10.1186/s12916-022-02715-4', 'article-title': 'Individual and neighborhood risk factors of hospital admission and ' 'death during the COVID-19 pandemic: a population-based cohort study', 'volume': '21', 'author': 'Bell', 'year': '2023', 'journal-title': 'BMC Med'}, { 'key': '2024081414092700600_ref27', 'article-title': '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', 'volume': '30', 'author': 'Wai', 'year': '2023', 'journal-title': 'Lancet Reg Health West Pac'}], 'container-title': 'Age and Ageing', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://academic.oup.com/ageing/article-pdf/53/8/afae180/58817538/afae180.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'syndication'}, { 'URL': 'https://academic.oup.com/ageing/article-pdf/53/8/afae180/58817538/afae180.pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 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