Abstract: The n e w e ng l a n d j o u r na l of m e dic i n e Original Article Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab Anil Gupta, M.D., Yaneicy Gonzalez‑Rojas, M.D., Erick Juarez, M.D., Manuel Crespo Casal, M.D., Jaynier Moya, M.D., Diego R. Falci, M.D., Ph.D., Elias Sarkis, M.D., Joel Solis, M.D., Hanzhe Zheng, Ph.D., Nicola Scott, M.Sc., Andrea L. Cathcart, Ph.D., Christy M. Hebner, Ph.D., Jennifer Sager, Ph.D., Erik Mogalian, Pharm.D., Ph.D., Craig Tipple, M.B., B.S., Ph.D., Amanda Peppercorn, M.D., Elizabeth Alexander, M.D., Phillip S. Pang, M.D., Ph.D., Almena Free, M.D., Cynthia Brinson, M.D., Melissa Aldinger, Pharm.D., and Adrienne E. Shapiro, M.D., Ph.D., for the COMET-ICE Investigators*​​ A BS T R AC T BACKGROUND Coronavirus disease 2019 (Covid-19) disproportionately results in hospitalization or death in older patients and those with underlying conditions. Sotrovimab is a pan-sarbecovirus monoclonal antibody that was designed to prevent progression of Covid-19 in high-risk patients early in the course of disease. METHODS In this ongoing, multicenter, double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, nonhospitalized patients with symptomatic Covid-19 (≤5 days after the onset of symptoms) and at least one risk factor for disease progression to receive a single infusion of sotrovimab at a dose of 500 mg or placebo. The primary efficacy outcome was hospitalization (for >24 hours) for any cause or death within 29 days after randomization. RESULTS In this prespecified interim analysis, which included an intention-to-treat population of 583 patients (291 in the sotrovimab group and 292 in the placebo group), 3 patients (1%) in the sotrovimab group, as compared with 21 patients (7%) in the placebo group, had disease progression leading to hospitalization or death (relative risk reduction, 85%; 97.24% confidence interval, 44 to 96; P = 0.002). In the placebo group, 5 patients were admitted to the intensive care unit, including 1 who died by day 29. Safety was assessed in 868 patients (430 in the sotrovimab group and 438 in the placebo group). Adverse events were reported by 17% of the patients in the sotrovimab group and 19% of those in the placebo group; serious adverse events were less common with sotrovimab than with placebo (in 2% and 6% of the patients, respectively). CONCLUSIONS Among high-risk patients with mild-to-moderate Covid-19, sotrovimab reduced the risk of disease progression. No safety signals were identified. (Funded by Vir Biotechnology and GlaxoSmithKline; COMET-ICE ClinicalTrials.gov number, NCT04545060.) From the Albion Finch Medical Centre, William Osler Health Centre, Toronto (A.G.); Optimus U (Y.G.-R.) and Florida International Medical Research (E.J.), Miami, Pines Care Research Center, Pembroke Pines (J.M.), and Sarkis Clinical Trials, Gainesville (E.S.) — all in Florida; Álvaro Cunqueiro Hospital, IIS Galicia Sur, Vigo, Spain (M.C.C.); Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil (D.R.F.); Centex Studies, McAllen (J. Solis), and Central Texas Clinical Research, Austin (C.B.) — both in Texas; Vir Biotechnology, San Francisco (H.Z., A.L.C., C.M.H., J. Sager, E.M., E.A., P.S.P., M.A.); GlaxoSmithKline, Stevenage, United Kingdom (N.S., C.T.); GlaxoSmithKline, Cambridge, MA (A.P.); Pinnacle Research Group, Anniston, AL (A.F.); and the Departments of Global Health and Medicine, University of Washington, and Fred Hutchinson Cancer Research..