Abstract: PLOS ONE RESEARCH ARTICLE The clinical effectiveness of REGEN-COV in SARS-CoV-2 infection with Omicron versus Delta variants Hayley B. Gershengorn ID1,2*, Samira Patel3, Tanira Ferreira1, Sankalp Das3, Dipen J. Parekh4, Bhavarth Shukla5 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, United States of America, 2 Division of Critical Care Medicine, Albert Einstein College of Medicine, Bronx, NY, United States of America, 3 Care Transformation, University of Miami Hospital and Clinics, Miami, FL, United States of America, 4 Department of Urology, University of Miami Miller School of Medicine, Miami, FL, United States of America, 5 Division of Infectious Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, United States of America * hbg20@med.miami.edu Abstract OPEN ACCESS Background Citation: Gershengorn HB, Patel S, Ferreira T, Das S, Parekh DJ, Shukla B (2022) The clinical effectiveness of REGEN-COV in SARS-CoV-2 infection with Omicron versus Delta variants. PLoS ONE 17(12): e0278770. https://doi.org/10.1371/ journal.pone.0278770 In vitro studies suggesting that REGEN-COV (casirivimab plus imdevimab monoclonal antibodies) had poor efficacy against Omicron-variant SARS-CoV-2 infection led to amendment of REGEN-COV’s Emergency Use Authorization to recommend use only in regions without high Omicron prevalence. REGEN-COV’s relative clinical effectiveness for Omicron is unknown. Editor: Vipa Thanachartwet, Mahidol University, Faculty of Tropical Medicine, THAILAND Methods and findings Received: July 26, 2022 Accepted: November 23, 2022 Published: December 2, 2022 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0278770 Copyright: © 2022 Gershengorn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: Data cannot be shared publicly because of HIPAA. Data are available from the University of Miami Institutional Data Access / Ethics Committee (contact via We conducted a retrospective cohort study of non-hospitalized adults who tested positive for SARS-CoV-2 by polymerase chain reaction at the University of Miami Health System from July 19 –November 21, 2021 (Delta period) and December 6, 2021 –January 7, 2022 (Omicron period). Subjects were stratified be REGEN-COV receipt within 72h of test positivity and by time period of infection. We constructed multivariable logistic regression models to assess the differential association of REGEN-COV receipt with hospitalization within 30 days (primary outcome) and ED presentation; all models included three exposure terms (REGEN-COV receipt, Omicron vs Delta period, interaction of REGEN-COV with time period) and potential confounders (vaccination status, vaccine boosting, cancer diagnosis). Our cohort consisted of 2,083 adults in the Delta period (213 [10.2%] received REGENCOV) and 4,201 in the Omicron period (156 [3.7%]..