{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:44:09Z","timestamp":1790765049510,"version":"4.1.0"},"reference-count":12,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Ritonavir-boosted nirmatrelvir and molnupiravir are currently used in the US and in other countries to treat nonhospitalized patients who have mild-to-moderate COVID-19 and who are at high risk for progression to severe disease. The associations of these 2 oral antiviral drugs with hospitalization and death resulting from infection with new SARS-CoV-2 Omicron subvariants, particularly BQ.1.1 and XBB.1.5, are unknown.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To assess the association of nirmatrelvir or molnupiravir use with the risks of hospitalization and death among patients infected with new Omicron subvariants.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This was a cohort study of patients who received a diagnosis of COVID-19 at Cleveland Clinic from April 1, 2022, to February 20, 2023 (during which the Omicron variant evolved from BA.2 to BA.4\/BA.5, then to BQ.1\/BQ.1.1, and finally to XBB\/XBB.1.5) and who were at high risk of progressing to severe disease, with follow-up through 90 days after diagnosis. The final date for follow-up data collection was February 27, 2023.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Treatment with ritonavir-boosted nirmatrelvir or molnupiravir.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was time to death. The secondary outcome was time to either hospitalization or death. The association of either nirmatrelvir or molnupiravir use with each outcome was measured by the hazard ratio (HR) adjusted for demographic factors, socioeconomic status, date of COVID-19 diagnosis, coexisting medical conditions, COVID-19 vaccination status, and previous SARS-CoV-2 infection.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n There were 68\u202f867 patients (29\u202f386 [42.7%] aged \u226565 years; 26\u202f755 [38.9%] male patients; 51\u202f452 [74.7%] non-Hispanic White patients). Thirty of 22\u202f594 patients treated with nirmatrelvir, 27 of 5311 patients treated with molnupiravir, and 588 of 40\u202f962 patients who received no treatment died within 90 days of Omicron infection. The adjusted HRs of death were 0.16 (95% CI, 0.11-0.23) for nirmatrelvir and 0.23 (95% CI, 0.16-0.34) for molnupiravir. The adjusted HRs of hospitalization or death were 0.63 (95% CI, 0.59-0.68) for nirmatrelvir and 0.59 (95% CI, 0.53-0.66) for molnupiravir. The associations of both drugs with both outcomes were observed across subgroups defined by age, race and ethnicity, date of COVID-19 diagnosis, vaccination status, previous infection status, and coexisting conditions.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n These findings suggest that the use of either nirmatrelvir or molnupiravir is associated with reductions in mortality and hospitalization in patients infected with Omicron, regardless of age, race and ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions. Both drugs can, therefore, be used to treat nonhospitalized patients who are at high risk of progressing to severe COVID-19.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.35077","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T11:01:58Z","timestamp":1695294118000},"page":"e2335077","source":"Crossref","is-referenced-by-count":55,"title":["Nirmatrelvir or Molnupiravir Use and Severe Outcomes From Omicron Infections"],"prefix":"10.1001","volume":"6","author":[{"given":"Dan-Yu","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Abi Fadel","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaiqi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex T.","family":"Milinovich","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gretchen L.","family":"Sacha","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Bartley","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijit","family":"Duggal","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2023,9,21]]},"reference":[{"issue":"6","key":"zoi231009r3","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1056\/NEJMoa2116044","article-title":"Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients.","volume":"386","author":"Jayk Bernal","year":"2022","journal-title":"N Engl J Med"},{"issue":"15","key":"zoi231009r4","doi-asserted-by":"publisher","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"},{"issue":"9","key":"zoi231009r5","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1056\/NEJMoa2204919","article-title":"Nirmatrelvir use and severe Covid-19 outcomes during the omicron surge.","volume":"387","author":"Arbel","year":"2022","journal-title":"N Engl J Med"},{"issue":"10359","key":"zoi231009r6","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1016\/S0140-6736(22)01586-0","article-title":"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.","volume":"400","author":"Wong","year":"2022","journal-title":"Lancet"},{"issue":"10373","key":"zoi231009r7","doi-asserted-by":"publisher","first-page":"281","DOI":"10.2139\/ssrn.4237902","article-title":"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.","volume":"401","author":"Butler","year":"2023","journal-title":"Lancet"},{"issue":"6","key":"zoi231009r9","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1016\/j.chest.2021.01.057","article-title":"Phenotypes and subphenotypes of patients with COVID-19: a latent class modeling analysis.","volume":"159","author":"Wang","year":"2021","journal-title":"Chest"},{"key":"zoi231009r10","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.annepidem.2018.11.008","article-title":"Material community deprivation and hospital utilization during the first year of life: an urban population-based cohort study.","volume":"30","author":"Brokamp","year":"2019","journal-title":"Ann Epidemiol"},{"key":"zoi231009r1","unstructured":"Food and Drug Administration. Fact sheet for healthcare providers: emergency use authorization for Paxlovid. December 2021. Revised May 2023. Accessed August 22, 2023. https:\/\/www.fda.gov\/media\/155050\/download"},{"key":"zoi231009r2","unstructured":"Food and Drug Administration. Fact sheet for healthcare providers: emergency use authorization for Lagevrio (molnupiravir) capsules. December 2021. Accessed August 22, 2023. https:\/\/www.fda.gov\/media\/155054\/download"},{"key":"zoi231009r8","unstructured":"Food and Drug Administration. Fact sheet for healthcare providers: emergency use authorization for bebtelovimab. November 4, 2022. Accessed August 22, 2023. https:\/\/www.fda.gov\/media\/156152\/download"},{"key":"zoi231009r11","unstructured":"Pfizer. Pfizer reports additional data on PAXLOVID\u2122 supporting upcoming new drug application submission to U.S. FDA. June 14, 2022. 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