Effectiveness of Sotrovimab in Preventing COVID-19-related Hospitalizations or Deaths Among U.S. Veterans

Background Data on effectiveness of sotrovimab preventing COVID-19-related hospitalization or mortality, particularly after the emergence of the Omicron variant, are limited. Method Determine the real-world clinical effectiveness of sotrovimab for prevention of 30-day COVID-19 related hospitalization or mortality using a retrospective cohort within the U.S. Department of Veterans Affairs (VA) healthcare system. Veterans aged ≥18 years, diagnosed with COVID-19 between December 1, 2021, and April 4, 2022, were included. Sotrovimab recipients (n=2,816) were exactly matched to untreated controls (n=11,250) on date of diagnosis, vaccination status, and region. The primary outcome was COVID-19-related hospitalization or all-cause mortality within 30 days from diagnosis. Cox proportional hazards modeling estimated the hazard ratios (HR) and 95% Confidence Interval (CI) for the association between receipt of sotrovimab and outcomes. Results During BA.1 dominance, compared to matched controls, sotrovimab-treated patients had a 70% lower risk hospitalization within 30 days or mortality (HR 0.30; 95%CI, 0.23-0.40), a 66% lower risk of 30-day hospitalization (HR 0.34; 95%CI, 0.25-0.46), and a 77% lower risk of 30-day all-cause mortality (HR 0.23; 95%CI, 0.14-0.38). During BA.2 dominance sotrovimab-treated patients had a 71% (HR .29; 95%CI, 0.08-0.98) lower risk of 30-day COVID-19-related-hospitalization, emergency, or urgent care. Limitations include confounding by indication. Conclusions Using national real-world data from high risk and predominantly vaccinated Veterans, administration of sotrovimab, compared with no treatment, was associated with reduced risk of 30-day COVID-19-related hospitalization or all-cause mortality during the Omicron BA.1 period and reduced risk of progression to severe COVID-19 during the BA.2 dominant period. Summary Examination of national real-world evidence demonstrates sotrovimab is effective in preventing at risk positive COVID-19 cases from progressing to severe SARS-CoV-2 infections compared to matched untreated cases during Delta and early Omicron variant waves in the U.S. Veteran population. ### Competing Interest Statement V.C.M. reports research grants from the CDC, Gilead Sciences, NIH, Veterans Affairs, and ViiV Healthcare; honoraria from Eli Lilly and Company; has served as an advisory board member for Eli Lilly and Company and Novartis; and has participated as a study section chair for the NIH.Y.Y.X., G.Z., C.K. reported receiving grants from the U.S. Food and Drug Administration through an interagency agreement with the Veterans Health Administration and from the U.S. Department of Veterans Affairs Office of Rural Health. Y.Y.X., G.Z., J.S. also reported receiving funding from Vir Biotechnology to U.S. Department of Veterans Affairs for other research projects outside the submitted work. Y.Y.X., V.C.M are supported by VA/BLRD VA SEQCURE (821-SD-ID-42403). V.C.M. received support from the Emory Center for AIDS Research (P30 AI050409). A.A.G. received COVID-19 research project funding from the National Institutes of Health, Department of Defense, Centers for Disease Control and Prevention, AbbVie, and Faron Pharmaceuticals, outside the submitted work. M.M.C., C.R., S.S. are employees of and shareholders of Vir Biotechnology. M.D. is employee of and shareholder of GSK. ### Funding Statement This study was supported by the Department of Veterans Affairs Office of Research and Development, the VA Office of Rural Health, Clinical Epidemiology Program at the White River Junction VA Medical Center, by Vir Biotechnology in collaboration with GSK, by resources and the use of facilities at the White River Junction VA Medical Center and VA Informatics and Computing Infrastructure, and data from the VA COVID-19 Shared Data Resource. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the institutional review board of the VA Medical Center in White River Junction, Vermont and was granted a waiver of informed consent because the study was deemed minimal risk and consent impractical to acquire. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Requests for access to the de-identified study data can be sent via e-mail to Yinong.Young-Xu@va.gov. No supporting documents will be made available. The data will be made available to qualified scientific researchers for specific purposes outlined in a proposal after the researcher enters into a standard data sharing agreement and the proposal is approved. Researchers must commit to transparency in publication.