Social Vulnerability and Rurality Associated With Higher SARS-CoV-2 Infection-Induced Seroprevalence: A Nationwide Blood Donor Study, United States, July 2020 – June 2021

Background: Most studies on health disparities during COVID-19 pandemic focused on reported cases and deaths and were limited in capturing disparities in true infection rates or the impact of social determinants of health. This nationwide study aimed to examine SARS-CoV-2 (the virus that causes COVID-19) antibody seroprevalence in the U.S. and its associations with rurality and social vulnerability over time. Methods: This repeated cross-sectional study used data from blood donations made July 2020 - June 2021 in 50 states and Washington, D.C. Donor ZIP codes were matched to counties and linked with Social Vulnerability Index (SVI) and urban-rural classification. SARS-CoV-2 antibody seroprevalences induced by infection and infection-vaccination combined were estimated. Association of infection-induced seropositivity with demographics, rurality, SVI, and its four themes were quantified using stratified analyses and multivariate regression models. Findings: Weighted seroprevalence differed significantly by race/ethnicity, age, rurality, and social vulnerability with distinct temporal trends. From July 2020 to June 2021, infection-induced seroprevalence increased from 1.6% to 27.2% in rural counties and from 3.7% to 20.0% in urban counties. However, in June 2021, the combined infection- and vaccination-induced seroprevalence in rural counties was lower (80.0% vs. 88.1%). Adjusting for covariates, higher infection-induced seropositivity was associated with being Hispanic and non-Hispanic Black, younger, and living in rural or higher socially vulnerable counties. Interpretation: The findings demonstrated continuously increasing SARS-CoV-2 seroprevalence in the U.S. across all geographic, demographic, and social sectors. Infection-induced seroprevalence rates were consistently higher among Hispanic and non-Hispanic Black donors, and those from rural or socially vulnerable counties. Vaccine-induced seroprevalence was lower in rural counties than urban counties. The findings illustrated disparities in SARS-CoV-2 infections in the U.S. independent of case-based surveillance and testing availability, identified areas for targeted vaccination strategies, and can inform efforts to reduce inequities and prepare for future outbreaks. Funding Information: This analysis did not have external funding sources Declaration of Interests: All coauthors declare no conflict of interests. Ethics Approval Statement: The study was approved by CDC as non-research public health surveillance based on anonymization of data and routine consent for blood donation testing that includes use of residual samples for research purposes. The study does not require human-subject research review nor clearance by the Office of Management and Budget and was conducted consistent with applicable federal law and CDC policy.