One Million and Counting: Estimates of Deaths in the United States from Ancestral SARS-CoV-2 and Variants

Background Over one million COVID-19 deaths have been recorded in the United States. Sustained global SARS-CoV-2 transmission has led to the emergence of new variants with increased transmissibility, virulence, and/or immune evasion. The specific burden of mortality from each variant over the course of the U.S. COVID-19 epidemic remains unclear. Methods We constructed an epidemiologic model using data reported by the CDC on COVID-19 mortality and circulating variant proportions to estimate the number of recorded COVID-19 deaths attributable to each SARS-CoV-2 variant in the U.S. We conducted sensitivity analysis to account for parameter uncertainty. Findings Of the 1,003,419 COVID-19 deaths recorded as of May 12, 2022, we estimate that 460,124 (46%) were attributable to WHO-designated variants. By U.S. Census Region, the South recorded the most variant deaths per capita (median estimate 158 per 100,000), while the Northeast recorded the fewest (111 per 100,000). Over 40 percent of national COVID-19 deaths were estimated to be caused by the combination of Alpha (median estimate 39,548 deaths), Delta (273,801), and Omicron (117,560). Interpretation SARS-CoV-2 variants that have emerged around the world have imposed a significant mortality burden in the U.S. In addition to national public health strategies, greater efforts are needed to lower the risk of new variants emerging, including through global COVID-19 vaccination, treatment, and outbreak mitigation. ### Competing Interest Statement N.D.G. is a consultant for Tempus Labs and the National Basketball Association for work related to COVID-19 but is outside the submitted work. V.P discloses reimbursement from Merck and Pfizer for travel to Scientific Input Engagements unrelated to COVID-19 and membership on the WHO Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC). ### Funding Statement This study did not receive any external funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the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 Datasets and R code needed to replicate this analysis are available online at [https://github.com/joewalker127/US\_Deaths\_COVID_Variants][1] [https://github.com/joewalker127/US\_Deaths\_COVID_Variants][1] [1]: https://github.com/joewalker127/US_Deaths_COVID_Variants