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Estimated US Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence Based on Blood Donations, July 2020-May 2021

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Based on blood donations in the US from July 2020 through May 2021, how did infection- and vaccine-induced SARS-CoV-2 seroprevalence vary over time by demographic group and by geographic region?

Findings  In this repeated cross-sectional study that included 1 443 519 blood donation specimens from a catchment area representing 74% of the US population, estimated SARS-CoV-2 seroprevalence weighted for differences between the study sample and general population increased from 3.5% in July 2020 to 20.2% for infection-induced antibodies and 83.3% for combined infection- and vaccine-induced antibodies in May 2021. Seroprevalence differed by age, race and ethnicity, and geographic region of residence, but these differences changed over the course of the study.

Meaning  Based on a sample of blood donations in the US from July 2020 through May 2021, estimated SARS-CoV-2 seroprevalence increased over time and varied by age, race and ethnicity, and geographic region.

Abstract

Importance  People who have been infected with or vaccinated against SARS-CoV-2 have reduced risk of subsequent infection, but the proportion of people in the US with SARS-CoV-2 antibodies from infection or vaccination is uncertain.

Objective  To estimate trends in SARS-CoV-2 seroprevalence related to infection and vaccination in the US population.

Design, Setting, and Participants  In a repeated cross-sectional study conducted each month during July 2020 through May 2021, 17 blood collection organizations with blood donations from all 50 US states; Washington, DC; and Puerto Rico were organized into 66 study-specific regions, representing a catchment of 74% of the US population. For each study region, specimens from a median of approximately 2000 blood donors were selected and tested each month; a total of 1 594 363 specimens were initially selected and tested. The final date of blood donation collection was May 31, 2021.

Exposure  Calendar time.

Main Outcomes and Measures  Proportion of persons with detectable SARS-CoV-2 spike and nucleocapsid antibodies. Seroprevalence was weighted for demographic differences between the blood donor sample and general population. Infection-induced seroprevalence was defined as the prevalence of the population with both spike and nucleocapsid antibodies. Combined infection- and vaccination-induced seroprevalence was defined as the prevalence of the population with spike antibodies. The seroprevalence estimates were compared with cumulative COVID-19 case report incidence rates.

Results  Among 1 443 519 specimens included, 733 052 (50.8%) were from women, 174 842 (12.1%) were from persons aged 16 to 29 years, 292 258 (20.2%) were from persons aged 65 years and older, 36 654 (2.5%) were from non-Hispanic Black persons, and 88 773 (6.1%) were from Hispanic persons. The overall infection-induced SARS-CoV-2 seroprevalence estimate increased from 3.5% (95% CI, 3.2%-3.8%) in July 2020 to 20.2% (95% CI, 19.9%-20.6%) in May 2021; the combined infection- and vaccination-induced seroprevalence estimate in May 2021 was 83.3% (95% CI, 82.9%-83.7%). By May 2021, 2.1 SARS-CoV-2 infections (95% CI, 2.0-2.1) per reported COVID-19 case were estimated to have occurred.

Conclusions and Relevance  Based on a sample of blood donations in the US from July 2020 through May 2021, vaccine- and infection-induced SARS-CoV-2 seroprevalence increased over time and varied by age, race and ethnicity, and geographic region. Despite weighting to adjust for demographic differences, these findings from a national sample of blood donors may not be representative of the entire US population.

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Article Information

Corresponding Author: Jefferson M. Jones, MD, MPH, CDR, US Public Health Service, Seroprevalence Team Lead, Epidemiology Task Force, Centers for Disease Control and Prevention COVID-19 Response, 1600 Clifton Rd NE, MS V18-4, Atlanta, GA 30329-4027 (ioe8@cdc.gov).

Accepted for Publication: August 19, 2021.

Published Online: September 2, 2021. doi:10.1001/jama.2021.15161

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, Sulaeman, Saa, Biggerstaff, Strauss, Destree, Nguyen, Weales, Brown, Gould, Miller, Fry, Hall, Gundlapalli, Basavaraju, Patton, Simmons, Thornburg, Kleinman, Stramer, Busch.

Acquisition, analysis, or interpretation of data: Jones, Stone, Sulaeman, Fink, Dave, Levy, Di Germanio, Green, Notari, Saa, Biggerstaff, Kessler, Vassallo, Reik, Rossmann, Nguyen, Sayers, Lough, Bougie, Ritter, Latoni, Sime, Gorlin, Brown, Berney, Benoit, Miller, Freeman, Kartik, Azziz-Baumgartner, Hall, MacNeil, Gundlapalli, Basavaraju, Gerber, Patton, Custer, Williamson, Simmons, Kleinman, Stramer, Opsomer, Busch.

Drafting of the manuscript: Jones, Saa, Ritter, Miller, Freeman, Kartik, Gundlapalli, Basavaraju, Stramer, Opsomer, Busch.

Critical revision of the manuscript for important intellectual content: Jones, Stone, Sulaeman, Fink, Dave, Levy, Di Germanio, Green, Notari, Saa, Biggerstaff, Strauss, Kessler, Vassallo, Reik, Rossmann, Destree, Nguyen, Sayers, Lough, Bougie, Ritter, Latoni, Weales, Sime, Gorlin, Brown, Gould, Berney, Benoit, Miller, Fry, Azziz-Baumgartner, Hall, MacNeil, Gundlapalli, Basavaraju, Gerber, Patton, Custer, Williamson, Simmons, Thornburg, Kleinman, Stramer, Busch.

Statistical analysis: Jones, Sulaeman, Levy, Biggerstaff, Berney, Freeman, Kartik, Opsomer, Busch.

Obtained funding: Stone, Saa, Gould, Hall, Patton, Simmons, Stramer, Busch.

Administrative, technical, or material support: Jones, Stone, Sulaeman, Fink, Dave, Levy, Di Germanio, Green, Notari, Saa, Strauss, Kessler, Vassallo, Reik, Rossmann, Destree, Nguyen, Sayers, Lough, Bougie, Ritter, Latoni, Weales, Sime, Gorlin, Brown, Gould, Berney, Benoit, Miller, Azziz-Baumgartner, Hall, Gundlapalli, Basavaraju, Gerber, Patton, Custer, Williamson, Simmons, Thornburg, Stramer, Busch.

Supervision: Jones, Stone, Sulaeman, Saa, Reik, Ritter, Gould, Fry, Hall, MacNeil, Gundlapalli, Patton, Custer, Thornburg, Stramer, Opsomer, Busch.

Conflict of Interest Disclosures: The Gulf Coast Regional Blood Center uses Roche assays for testing and Dr Rossmann reported serving as principal investigator on Roche blood donor testing, for which she received no direct compensation outside the submitted work. Dr Sime reported collecting convalescent plasma from blood donors for LifeServe Blood Center during the time samples were collected outside the submitted work. Dr Kartik reported receiving personal fees from Brigham and Women’s Hospital and PathAI outside the submitted work. Dr Custer reported receiving personal fees and grants from Grifols Diagnostic Solutions outside the submitted work. Dr Kleinman reported receiving personal fees from Creative Testing Solutions and Roche Molecular Systems outside the submitted work. Dr Stramer reported receiving a contract from the 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 in the past 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 members from Vitalant Research Institute, Westat, the American Red Cross, each of the 17 participating blood collection organizations and 10 testing laboratories, and Georgia Tech Research Institute for their assistance on this study.

References
1.
Centers for Disease Control and Prevention. COVID data tracker. Accessed July 30, 2021. https://covid.cdc.gov/covid-data-tracker/
2.
Reese  H , Iuliano  AD , Patel  NN ,  et al.  Estimated incidence of coronavirus disease 2019 (COVID-19) illness and hospitalization: United States, February-September, 2020.   Clin Infect Dis. 2021;72(12):e1010-e1017. doi:10.1093/cid/ciaa1780 PubMedGoogle ScholarCrossref
3.
Petersen  LR , Sami  S , Vuong  N ,  et al.  Lack of antibodies to SARS-CoV-2 in a large cohort of previously infected persons.   Clin Infect Dis. Published November 4, 2020. PubMedGoogle Scholar
4.
Busch  MP , Stone  M .  Serosurveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incidence using global blood donor populations.   Clin Infect Dis. 2021;72(2):254-256. doi:10.1093/cid/ciaa1116 PubMedGoogle ScholarCrossref
5.
Krammer  F , Srivastava  K , Alshammary  H ,  et al.  Antibody responses in seropositive persons after a single dose of SARS-CoV-2 mRNA vaccine.   N Engl J Med. 2021;384(14):1372-1374. doi:10.1056/NEJMc2101667 PubMedGoogle ScholarCrossref
6.
National Institutes of Health. COVID-19 SeroHub. Accessed July 30, 2021. https://covid19serohub.nih.gov/
7.
World Health Organization. SeroTracker. Accessed June 17, 2021. https://serotracker.com/
8.
Dodd  RY , Xu  M , Stramer  SL .  Change in donor characteristics and antibodies to SARS-CoV-2 in donated blood in the US, June-August 2020.   JAMA. 2020;324(16):1677-1679. doi:10.1001/jama.2020.18598 PubMedGoogle ScholarCrossref
9.
HHS Regulations for the Protection of Human Subjects in Research. 45 CFR §46 (2018).
10.
Institutional Review Boards. 21 CFR §56 (2020).
11.
Protection of privacy of individuals who are research subjects, 42 USC §241(d) (2011).
12.
Records maintained on individuals, 5 USC §552a (2010).
13.
Paperwork Reduction Act, 44 USC §3501 et seq (1995).
14.
Stone  M , Di Germanio  C , Wright  DJ ,  et al; NHLBI Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P).  Use of US blood donors for national serosurveillance of SARS-CoV-2 antibodies: basis for an expanded national donor serosurveillance program.   Clin Infect Dis. Published June 10, 2021. doi:10.1093/cid/ciab537 PubMedGoogle Scholar
15.
Peluso  MJ , Takahashi  S , Hakim  J ,  et al.  SARS-CoV-2 antibody magnitude and detectability are driven by disease severity, timing, and assay.   Sci Adv. 2021;7(31):eabh3409. doi:10.1126/sciadv.abh3409PubMedGoogle Scholar
17.
Takahashi  S , Greenhouse  B , Rodríguez-Barraquer  I .  Are seroprevalence estimates for severe acute respiratory syndrome coronavirus 2 biased?   J Infect Dis. 2020;222(11):1772-1775. doi:10.1093/infdis/jiaa523 PubMedGoogle ScholarCrossref
18.
Centers for Disease Control and Production. US COVID-19 vaccine product information. Accessed July 30, 2021. https://www.cdc.gov/vaccines/covid-19/info-by-product/index.html
19.
Atsma  F , Veldhuizen  I , Verbeek  A , de Kort  W , de Vegt  F .  Healthy donor effect: its magnitude in health research among blood donors.   Transfusion. 2011;51(8):1820-1828. doi:10.1111/j.1537-2995.2010.03055.x PubMedGoogle ScholarCrossref
20.
US Census Bureau. American Community Survey data. Accessed December 10, 2020. https://www.census.gov/programs-surveys/acs/data.html
21.
Rust  KF , Rao  JN .  Variance estimation for complex surveys using replication techniques.   Stat Methods Med Res. 1996;5(3):283-310. doi:10.1177/096228029600500305 PubMedGoogle ScholarCrossref
22.
Cromer  D , Juno  JA , Khoury  D ,  et al.  Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection.   Nat Rev Immunol. 2021;21(6):395-404. doi:10.1038/s41577-021-00550-x PubMedGoogle ScholarCrossref
23.
Centers for Disease Control and Prevention. Science brief: COVID-19 vaccines and vaccination. Accessed July 16, 2021. https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/fully-vaccinated-people.html
24.
Feng  S , Phillips  DJ , White  T ,  et al; Oxford COVID Vaccine Trial Group.  Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection.   medRxiv. Published June 24, 2021. doi:10.1101/2021.06.21.21258528Google Scholar
25.
Khoury  DS , Cromer  D , Reynaldi  A ,  et al.  Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection.   Nat Med. 2021;27(7):1205-1211. doi:10.1038/s41591-021-01377-8 PubMedGoogle ScholarCrossref
26.
Bergwerk  M , Gonen  T , Lustig  Y ,  et al.  COVID-19 breakthrough infections in vaccinated health care workers.   N Engl J Med. Published July 28, 2021. doi:10.1056/NEJMoa2109072 PubMedGoogle Scholar
27.
Pingali  C , Meghani  M , Razzaghi  H ,  et al.  COVID-19 vaccination coverage among insured persons aged ≥16 years, by race/ethnicity and other selected characteristics - eight integrated health care organizations, United States, December 14, 2020-May 15, 2021.   MMWR Morb Mortal Wkly Rep. 2021;70(28):985-990. doi:10.15585/mmwr.mm7028a1 PubMedGoogle ScholarCrossref
28.
Anand  S , Montez-Rath  M , Han  J ,  et al.  Prevalence of SARS-CoV-2 antibodies in a large nationwide sample of patients on dialysis in the USA: a cross-sectional study.   Lancet. 2020;396(10259):1335-1344. doi:10.1016/S0140-6736(20)32009-2 PubMedGoogle ScholarCrossref
29.
Bajema  KL , Wiegand  RE , Cuffe  K ,  et al.  Estimated SARS-CoV-2 seroprevalence in the US as of September 2020.   JAMA Intern Med. 2020;181(4):450-460. doi:10.1001/jamainternmed.2020.7976PubMedGoogle ScholarCrossref
30.
Hutchins  HJ , Wolff  B , Leeb  R ,  et al.  COVID-19 mitigation behaviors by age group: United States, April-June 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(43):1584-1590. doi:10.15585/mmwr.mm6943e4 PubMedGoogle ScholarCrossref
31.
Wong  LSY , Loo  EXL , Kang  AYH , Lau  HX , Tambyah  PA , Tham  EH .  Age-related differences in immunological responses to SARS-CoV-2.   J Allergy Clin Immunol Pract. 2020;8(10):3251-3258. doi:10.1016/j.jaip.2020.08.026 PubMedGoogle ScholarCrossref
32.
Centers for Disease Control and Prevention. Interim guidance for SARS-CoV-2 testing and screening at institutions of higher education (IHEs). Accessed July 30, 2021. https://www.cdc.gov/coronavirus/2019-ncov/community/colleges-universities/ihe-testing.html
33.
Centers for Disease Control and Prevention. Testing guidelines for nursing homes. Accessed July 30, 2021. https://www.cdc.gov/coronavirus/2019-ncov/hcp/nursing-homes-testing.html
34.
Pray  IW , Ford  L , Cole  D ,  et al; CDC COVID-19 Surge Laboratory Group.  Performance of an antigen-based test for asymptomatic and symptomatic SARS-CoV-2 testing at two university campuses: Wisconsin, September-October 2020.   MMWR Morb Mortal Wkly Rep. 2021;69(5152):1642-1647. doi:10.15585/mmwr.mm695152a3 PubMedGoogle ScholarCrossref
35.
US Food and Drug Administration. Updated information for blood establishments regarding the COVID-19 pandemic and blood donation. Accessed March 30, 2021. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/updated-information-blood-establishments-regarding-covid-19-pandemic-and-blood-donation
36.
Bone  A , Guthmann  JP , Assal  A ,  et al.  Incidence of H1N1 2009 virus infection through the analysis of paired plasma specimens among blood donors, France.   PLoS One. 2012;7(3):e33056. doi:10.1371/journal.pone.0033056 PubMedGoogle Scholar
37.
Diesel  J , Sterrett  N , Dasgupta  S ,  et al.  COVID-19 vaccination coverage among adults: United States, December 14, 2020-May 22, 2021.   MMWR Morb Mortal Wkly Rep. 2021;70(25):922-927. doi:10.15585/mmwr.mm7025e1 PubMedGoogle ScholarCrossref
38.
Patel  EU , Bloch  EM , Grabowski  MK ,  et al.  Sociodemographic and behavioral characteristics associated with blood donation in the United States: a population-based study.   Transfusion. 2019;59(9):2899-2907. doi:10.1111/trf.15415 PubMedGoogle ScholarCrossref
39.
Barry  V , Dasgupta  S , Weller  DL ,  et al.  Patterns in COVID-19 vaccination coverage, by social vulnerability and urbanicity: United States, December 14, 2020-May 1, 2021.   MMWR Morb Mortal Wkly Rep. 2021;70(22):818-824. doi:10.15585/mmwr.mm7022e1 PubMedGoogle ScholarCrossref
40.
Karmakar  M , Lantz  PM , Tipirneni  R .  Association of social and demographic factors with COVID-19 incidence and death rates in the US.   JAMA Netw Open. 2021;4(1):e2036462. doi:10.1001/jamanetworkopen.2020.36462 PubMedGoogle Scholar
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