{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T20:43:00Z","timestamp":1781901780894,"version":"3.54.5"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immunocompromised patients, especially those receiving B\u2013cell\u2013depleting therapy (BCDT), remain at high risk for severe coronavirus disease 2019 (COVID\u201319). Although monoclonal antibodies showed benefit pre\u2013Omicron, the real\u2013world effectiveness of the oral antivirals in BCDT recipients is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We emulated a target trial using the Cleveland Clinic electronic health record. Adult patients (\u226518\u2005years) with immune\u2013mediated inflammatory diseases who received rituximab or ocrelizumab and tested positive for severe acute respiratory syndrome coronavirus 2 between 19 December 2021 and 30 June 2025 were eligible. The primary endpoint was hospitalization or death within 21\u2005days; the secondary endpoint was death within 90\u2005days. Propensity scores adjusted for confounding, and Weighted Cox regression models were used to evaluated treatment effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 255 853 COVID\u201319 cases, 876 met criteria for the nirmatrelvir\/ritonavir cohort (411 treated, 465 untreated) and 566 for the molnupiravir cohort (91 treated, 475 untreated). In the nirmatrelvir\/ritonavir cohort, 18 (4.4%) of treated versus 43 (9.2%) of untreated patients were hospitalized or died within 21\u2005days. After weighting, nirmatrelvir\/ritonavir reduced the hazard by 44% (hazard ratio [HR], 0.56; 95% confidence interval [CI], \u202f0.31\u20130.99). In the molnupiravir cohort, 6 (6.6%) of treated and 46 (9.7%) of untreated patients met the primary endpoint; the weighted HR was 0.56 (95% CI, 0.24\u20131.33), not statistically significant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Early outpatient nirmatrelvir\/ritonavir significantly lowers the risk of COVID\u201319\u2013related hospitalization or death in patients on BCDT. Molnupiravir showed a nonsignificant trend toward benefit. These findings support prioritizing nirmatrelvir\/ritonavir for high\u2013risk immunocompromised populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciaf521","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T12:23:25Z","timestamp":1761222205000},"page":"1065-1073","source":"Crossref","is-referenced-by-count":3,"title":["Effectiveness of Nirmatrelvir\/Ritonavir or Molnupiravir Use in Immunocompromised Patients on B-Cell\u2013Depleting Therapy With COVID-19: A Target Trial Emulation Study"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8773-7739","authenticated-orcid":false,"given":"Cassandra","family":"Calabrese","sequence":"first","affiliation":[{"name":"Department of Rheumatologic and Immunologic Diseases, Cleveland Clinic , Cleveland, Ohio ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4663-6202","authenticated-orcid":false,"given":"Yifan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Cleveland Clinic , Cleveland, Ohio ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijit","family":"Duggal","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Cleveland Clinic , Cleveland, Ohio ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5161-246X","authenticated-orcid":false,"given":"Shuaiqi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Cleveland Clinic , Cleveland, Ohio ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2569-5334","authenticated-orcid":false,"given":"Yiying","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Cleveland Clinic , Cleveland, Ohio ,","place":["USA"]},{"name":"Department of Mathematics and Statistics, Cleveland State University , Cleveland, Ohio ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shravan","family":"Kethireddy","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Cleveland Clinic , Cleveland, Ohio ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0070-8100","authenticated-orcid":false,"given":"Gretchen L","family":"Sacha","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Cleveland Clinic , Cleveland, Ohio ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Department of Rheumatologic and Immunologic Diseases, Cleveland Clinic , Cleveland, Ohio ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8212-6931","authenticated-orcid":false,"given":"Xiaofeng F","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Cleveland Clinic , Cleveland, Ohio ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"2026020907383293900_ciaf521-B1","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.cmi.2023.03.017","article-title":"Clinical outcomes of the severe acute respiratory syndrome coronavirus 2 Omicron and Delta variant: systematic review and meta-analysis of 33 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COVID-19 Global Rheumatology Alliance physician registry","volume":"80","author":"Sparks","year":"2021","journal-title":"Ann Rheum Dis"},{"key":"2026020907383293900_ciaf521-B10","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1002\/art.42287","article-title":"Breakthrough SARS-CoV-2 infections in patients with immune-mediated disease undergoing B cell-depleting therapy: a retrospective cohort analysis","volume":"74","author":"Calabrese","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"2026020907383293900_ciaf521-B11","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1080\/23744235.2023.2276784","article-title":"Clinical outcomes and immunological features of COVID-19 patients receiving B-cell depletion therapy during the Omicron era","volume":"56","author":"Lee","year":"2024","journal-title":"Infect 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