{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T07:41:25Z","timestamp":1787557285926,"version":"build-2736575974"},"reference-count":84,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":29,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Australian Partnership for Preparedness Research on Infectious Disease Emergencies"},{"name":"APPRISE"},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Randomized controlled trials (RCTs) of oral antivirals for COVID-19 conducted early in the pandemic had favorable results in unvaccinated populations. We conducted a systematic review and meta-analysis of the effectiveness of nirmatrelvir-ritonavir and molnupiravir against hospitalization and death in vaccinated populations in the post-Omicron era.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically searched PubMed, Embase and the Cochrane library for RCTs conducted from January 2020, and observational studies in adults who were vaccinated conducted from January 2022. We performed a random effects meta-analysis using the inverse variance method with subgroup analysis by age (&amp;lt;65 vs \u226565 years) and study quality (excluding vs including studies at serious risk of bias).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 43 studies (8 RCTs, 35 observational). Two RCTs were in vaccinated populations in which no association between treatment with nirmatrelvir-ritonavir and a reduction in death, or treatment with molnupiravir and a reduction in hospitalization or death, was observed. In the meta-analysis of observational studies, nirmatrelvir-ritonavir was associated with a reduction in hospitalization (n = 11; odds ratio (OR): 0.60; 95% CI .54\u2013.67, hazard ratio (HR): 0.69; 95% CI .62\u2013.76) and mortality (n = 9; OR: 0.33, 95% CI .22\u2013.48; HR: 0.56, 95% CI .36\u2013.87). Molnupiravir was not associated with a significant reduction in hospitalization (n = 5; OR = 0.83; 95% CI .65\u20131.07) with mixed results for mortality (n = 9; OR = 0.61; 95% CI .41\u2013.91; HR = 0.65; 95% CI .42\u20131.01).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In vaccinated populations, RCTs have not demonstrated a reduction in hospitalization or death among populations treated with nirmatrelvir-ritonavir or with molnupiravir. However, RCTs of nirmatrelvir-ritonavir had limited statistical power to detect clinically important differences. Observational studies of nirmatrelvir-ritonavir, but not molnupiravir, consistently suggested a benefit against these outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trail Registration<\/jats:title>\n                    <jats:p>PROSPERO (CRD420251266532)<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ofid\/ofag339","type":"journal-article","created":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T11:34:39Z","timestamp":1780227279000},"source":"Crossref","is-referenced-by-count":1,"title":["Evaluating the Effectiveness of Antivirals for COVID-19 in the Post-vaccine, Omicron Era: A Systematic Review and Meta-analysis"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3984-6017","authenticated-orcid":false,"given":"Laura J","family":"Edwards","sequence":"first","affiliation":[{"name":"School of Population Health, UNSW Sydney , Sydney, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bette","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Population Health, UNSW Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"National Centre for Immunisation Research and Surveillance , Sydney, New South Wales ,","place":["Australia"]},{"name":"Faculty of Medicine and Health, University of Sydney , Sydney, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James G","family":"Wood","sequence":"additional","affiliation":[{"name":"School of Population Health, UNSW Sydney , Sydney, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Stephens","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Tasmania , Hobart, Tasmania ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen C","family":"Cheng","sequence":"additional","affiliation":[{"name":"Infectious Diseases, Monash Health , Melbourne, Victoria ,","place":["Australia"]},{"name":"School of Clinical Sciences, Monash University , Melbourne, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"2026073009015915000_ofag339-B1","author":"World Health Organization"},{"key":"2026073009015915000_ofag339-B2","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41586-020-2521-4","article-title":"Factors associated with COVID-19-related death using OpenSAFELY","volume":"584","author":"Williamson","year":"2020","journal-title":"Nature"},{"key":"2026073009015915000_ofag339-B3","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1186\/s12879-021-06378-z","article-title":"High risk groups for severe COVID-19 in a whole of population cohort in Australia","volume":"21","author":"Liu","year":"2021","journal-title":"BMC Infect Dis"},{"key":"2026073009015915000_ofag339-B4","author":"Global Burden of Disease 2023"},{"key":"2026073009015915000_ofag339-B5","author":"US Food and Drug Association"},{"key":"2026073009015915000_ofag339-B6","author":"US Food and Drug Administration"},{"key":"2026073009015915000_ofag339-B7","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2023.1253799","article-title":"Adverse events associated with molnupiravir: a real-world disproportionality analysis in food and drug administration adverse event reporting system","volume":"14","author":"Liang","year":"2023","journal-title":"Front Pharmacol"},{"key":"2026073009015915000_ofag339-B8","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.15585\/mmwr.mm7143a3","article-title":"Notes from the field: dispensing of oral antiviral drugs for treatment of COVID-19 by Zip code\u2013level social vulnerability\u2014United States, December 23, 2021\u2013August 28, 2022","volume":"71","author":"Sullivan","year":"2022","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2026073009015915000_ofag339-B9","author":"Australian Government Department of Health Disability and Ageing"},{"key":"2026073009015915000_ofag339-B10","author":"NHS England"},{"key":"2026073009015915000_ofag339-B11","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.4269\/ajtmh.21-1339","article-title":"Making statistical sense of the molnupiravir MOVe-OUT clinical trial","volume":"106","author":"Thorlund","year":"2022","journal-title":"Am J Trop Med Hyg"},{"key":"2026073009015915000_ofag339-B12","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1093\/jac\/dkac440","article-title":"Evaluation of publication bias for 12 clinical trials of molnupiravir to treat SARS-CoV-2 infection in 13694 patients with meta-analysis","volume":"78","author":"Lawrence","year":"2023","journal-title":"J Antimicrob 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