Abstract: RESEARCH ARTICLE Sotrovimab in Hospitalized Patients with SARS-CoV-2 Omicron Variant Infection: a Propensity Score-Matched Retrospective Cohort Study Marcel S. Woo,a,b Thomas Theo Brehm,c,d Marlene Fischer,e Andreas Heyer,c Dominic Wichmann,e Sabine Jordan,c Dominik Nörz,f Marc Lütgehetmann,d,f Marylyn M. Addo,c,d,g Ansgar W. Lohse,c,d Stefan Schmiedel,c,d Stefan Kluge,e Julian Schulze zur Wieschc,d Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany a Institute of Neuroimmunology and Multiple Sclerosis (INIMS), Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany b c I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany German Center for Infection Research (DZIF), University Medical Center Hamburg-Eppendorf, Lübeck-Borstel-Riems, Hamburg, Germany d Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany e Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany f Institute of Infection Research and Vaccine Development (IIRVD), University Medical Center Hamburg-Eppendorf, Hamburg, Germany g Marcel S. Woo, Thomas Theo Brehm, Stefan Kluge, and Julian Schulze zur Wiesch contributed equally to this article. Author order was determined in order of increasing seniority. In vitro data suggest the monoclonal antibody sotrovimab may have lost inhibitory capability against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) Omicron variant. We aimed to provide real-life data on clinical outcomes in hospitalized patients. We retrospectively analyzed patients who were treated at the University Medical Center Hamburg-Eppendorf, Germany, between December 2021 and June 2022. Out of all 1,254 patients, 185 were treated with sotrovimab: 147 patients received sotrovimab monotherapy, and 38 received combination treatment with sotrovimab and remdesivir. We compared in-hospital mortality for the different treatment regimens for patients treated on regular wards and the intensive care unit separately and performed propensity score matching by age, sex, comorbidities, immunosuppression, and additional dexamethasone treatment to select patients who did not receive antiviral treatment for comparison. No difference in in-hospital mortality was observed between any of the treatment groups and the respective control groups. These findings underline that sotrovimab adds no clinical benefit for hospitalized patients with SARS-CoV-2 Omicron variant infections. IMPORTANCE This study shows that among hospitalized patients with SARS-CoV-2 Omicron variant infection at risk of disease progression, treatment with sotrovimab alone or in combination with remdesivir did not decrease in-hospital mortality. These real-world clinical findings in combination with previous in vitro data about lacking neutralizing activity of sotrovimab against SARS-CoV-2 Omicron variant do not support sotrovimab as a treatment option in these patients. KEYWORDS SARS-CoV-2, COVID-19, Omicron, sotrovimab, remdesivir, monoclonal antibodies, Omicron variant A s of September 2022, more than 6.4 million people have died from coronavirus disease 2019 (COVID-19) worldwide (1). The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) Omicron variant (B.1.1.529) emerged in November 2021 and quickly replaced the Delta variant..