Abstract: medRxiv preprint doi: https://doi.org/10.1101/2022.06.17.22276575; this version posted June 18, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 1 2 Change in Effectiveness of Sotrovimab for Preventing Hospitalization and Mortality in COVID-19 Outpatients During the Omicron Phase 3 4 Neil R. Aggarwal, MD, MHSca*; Laurel E. Beaty, MSb*; Tellen D. Bennett, MD, MS c,e; Nichole E. Carlson, PhD, MSb,e; Adit A. Ginde, MD, MPHd,e 5 a Department of Medicine, University of Colorado School of Medicine, Aurora, 80045, USA 6 7 b 8 9 c Section of Informatics and Data Science, Department of Pediatrics, University of Colorado Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, 80045, USA School of Medicine, Aurora, 80045, USA 10 11 d 12 13 e Colorado Clinical and Translational Sciences Institute, University of Colorado Anschutz 14 * Contributed equally to this manuscript 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 See Supplement for a full list of Contributors. Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, 80045, USA Medical Campus, Aurora, 80045, USA Corresponding author: Neil R. Aggarwal, MD, MHSc Department of Medicine University of Colorado School of Medicine 12700 E. 19th Ave, Mail Stop C-272 Aurora, CO 80045, USA Phone: +1-303-724-6038 Email: neil.aggarwal@cuanschutz.edu Running title: Sotrovimab for COVID-19 Outpatients Word counts: Abstract: 199, Manuscript text: 2924 Summary: Real-world evidence demonstrates that the neutralizing monoclonal antibody sotrovimab was not associated with lower 28-day hospitalization and mortality rates when administered to high-risk outpatients recently infected with SARS-CoV-2 during the Omicron variant phase, compared to a propensity-matched cohort of untreated outpatients. NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. 1 medRxiv preprint doi: https://doi.org/10.1101/2022.06.17.22276575; this version posted June 18, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 33 ABSTRACT 34 Background: Sotrovimab, a neutralizing monoclonal antibody (mAb) treatment authorized for 35 early symptomatic COVID-19 patients, was effective in preventing the progression of severe 36 disease and mortality following SARS-CoV-2 Delta variant infection. It is not known whether 37 sotrovimab is similarly effective for SARS-CoV-2 Omicron variant infection. 38 Methods: Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 39 infection from December 26, 2021 to March 10, 2022 (>96% Omicron BA.1 variant), using 40 electronic health records from a statewide health system linked to state-level vaccine and 41 mortality data. We used propensity matching to select up to 3 patients not receiving mAbs or 42 other authorized antivirals for each patient who received outpatient sotrovimab treatment. The 43 primary outcome was 28-day hospitalization; secondary outcomes included mortality. To 44 evaluate change in..