By testing for both SARS-CoV-2 spike and nucleocapsid antibodies, seroprevalence studies can estimate the proportion of a population with antibodies from previous infection (nucleocapsid antibody or infection-induced seroprevalence) and from infection or vaccination (spike antibody or combined infection- and vaccine-induced seroprevalence). US seroprevalence from July 2020 to May 2021 based on blood donations was reported previously.1 This report includes monthly estimates through the conclusion of the study in December 2021.
Methods were previously described.1 Briefly, this repeated cross-sectional study included monthly blood donations from individuals aged 16 years and older from 66 study regions that included all 50 states; Washington, DC; and Puerto Rico. Specimens were tested for spike and nucleocapsid antibodies with total immunoglobulin assays (eMethods in the Supplement). Results were weighted to account for demographic differences between donors and the general population. Seroprevalence in December 2021 and changes between May and December 2021 were estimated by age, sex, race and ethnicity, and census region. (See Figure 1 legend for information on race and ethnicity.)
Increases in infection-induced seroprevalence from January through December 2021 were compared with vaccination rates. Fully vaccinated was defined as receipt of at least 2 messenger RNA COVID-19 vaccine doses or at least 1 dose of Ad26.COV2.S (Janssen) according to data reported to the Centers for Disease Control and Prevention. The fully vaccinated rate was measured as of December 31, 2021, among adults aged 18 years or older residing in counties corresponding to each study region. Correlation between vaccination rates and increases in seroprevalence were assessed via linear regression. Analyses were conducted with R version 4.1.2. Significance was tested with a 2-sided t test on the regression slope coefficient, with P < .05 considered significant. This study was approved by institutional review boards of the University of California, San Francisco and Westat as non–human participants research.
Between July 2020 and December 2021, among 2 408 093 included specimens, 1 210 270 (50.3%) were donated by women, 2 034 035 (84.5%) by non-Hispanic White donors, 293 234 (12.2%) by people aged 16 to 29 years, 512 600 (21.3%) by those aged 65 years or older, and 2 102 626 (87.3%) by those who had donated previously. From May through December 2021, the infection-induced seroprevalence increased from 20.2% (95% CI, 19.9%-20.6%) to 28.8% (95% CI, 28.4%-29.2%) and the combined seroprevalence from 83.3% (82.9%-83.7%) to 94.7% (95% CI, 94.5%-94.9%) (Figure 1). In December 2021, the infection-induced seroprevalence was highest in people aged 16 to 29 years (40.0% [95% CI, 38.9%-41.0%]), in non-Hispanic Black (32.5% [95% CI, 30.4%-34.6%]) and Hispanic (40.2% [95% CI, 38.6%-41.9%]) populations, and in people living in the South (33.5% [95% CI, 32.8%-34.1%]) and Midwest (31.7% [95% CI, 30.8%-32.6%]) (Figure 1). All demographic groups had a combined seroprevalence of 92.9% or more.
Higher vaccination rates correlated with a smaller increase in infection-induced seroprevalence (regression line slope = −0.32; P < .001) (Figure 2). During 2021, infection-induced seroprevalence increased by 10.64% (95% CI, 10.62%-10.66%) in study regions with greater than 80% rates of fully vaccinated populations, whereas in those with less than 60% fully vaccinated populations it increased by 19.84% (95% CI, 19.82%-19.86%).
In this study of US blood donations, the combined seroprevalence from infection or vaccination reached 94.7% by December 2021. Despite this, record levels of infection and reinfections were reported as the Omicron variant became predominant in early 2022.2 The high infection rates are likely related to increased transmissibility and enhanced immune escape mutations of the Omicron variant, along with waning protection from previous vaccination and infection.3-5 During 2021, the infection-induced seroprevalence increased more in regions with low vaccination rates compared with those with high ones. The ability of SARS-CoV-2 variants to cause widespread transmission in the setting of high seroprevalence illustrates the value of COVID-19 vaccines, including recommended booster doses, to maximize protection.
Study limitations include that seroprevalence in blood donors might not represent the seroprevalence in the general population, children were not included, and the association of lower vaccination rates and increases in seroprevalence does not prove causality and might be confounded by increased adherence to nonpharmaceutical interventions in study regions with higher vaccination rates.1
Accepted for Publication: May 24, 2022.
Published Online: June 13, 2022. doi:10.1001/jama.2022.9745
Corresponding Author: Jefferson M. Jones, MD, MPH, Centers for Disease Control and Prevention, MS V18-4, 1600 Clifton Rd NE, Atlanta, GA 30329-4027 (firstname.lastname@example.org).
Author Contributions: Dr Opsomer had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Jones, Stone, Stramer, Busch.
Acquisition, analysis, or interpretation of data: Jones, Opsomer, Stone, Benoit, Ferg, Stramer, Busch.
Drafting of the manuscript: Jones, Opsomer, Stramer, Busch.
Critical revision of the manuscript for important intellectual content: Jones, Stone, Benoit, Ferg, Stramer, Busch.
Statistical analysis: Opsomer, Ferg, Busch.
Obtained funding: Jones, Stone, Busch.
Administrative, technical, or material support: Jones, Stone, Benoit, Stramer, Busch.
Supervision: Jones, Stone, Stramer, Busch.
Conflict of Interest Disclosures: Dr Stramer reported receiving a contract from the Centers for Disease Control and Prevention (CDC) via Vitalant Research Institute outside the submitted work. Dr Busch reported being an employee of Vitalant Research Institute and serving on the medical advisory board for Creative Testing Systems; Vitalant Research Institute receives research funds and reagents for studies from Ortho and Roche and Dr Busch has presented on behalf of both companies at meetings, with travel support, but does not receive personal compensation from these or other SARS-CoV-2 test-manufacturing companies. No other disclosures were reported.
Funding/Support: This study was funded by the CDC.
Role of the Funder/Sponsor: CDC employees contributed to the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The CDC did not have the right to veto publication or to control the decision regarding to which journal the study was submitted.
Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC.
Additional Contributions: We thank Dane Freeman, PhD, Georgia Tech Research Institute, for graphic assistance; he was compensated for his role in the study. We thank members from Vitalant Research Institute, Westat, American Red Cross, Georgia Tech Research Institute, all participating blood collection organizations, and all testing laboratories for their assistance on this project (see Supplement for organization and names of the National Blood Donor Seroprevalence Study team). Finally, we thank all blood donors who contributed to this study.
et al. Waning 2-dose and 3-dose effectiveness of mRNA vaccines against COVID-19–associated emergency department and urgent care encounters and hospitalizations among adults during periods of Delta and Omicron variant predominance—VISION Network, 10 states, August 2021-January 2022. MMWR Morb Mortal Wkly Rep
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