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. 2021 Oct 12;326(14):1400-1409.
doi: 10.1001/jama.2021.15161.

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

Jefferson M Jones  1 , Mars Stone  2 , Hasan Sulaeman  2 , Rebecca V Fink  3 , Honey Dave  2 , Matthew E Levy  3 , Clara Di Germanio  2 , Valerie Green  4 , Edward Notari  5 , Paula Saa  6 , Brad J Biggerstaff  1 , Donna Strauss  7 , Debra Kessler  7 , Ralph Vassallo  2 , Rita Reik  8 , Susan Rossmann  9 , Mark Destree  10 , Kim-Anh Nguyen  11 , Merlyn Sayers  12 , Chris Lough  13 , Daniel W Bougie  14 , Megan Ritter  15 , Gerardo Latoni  16 , Billy Weales  17 , Stacy Sime  18 , Jed Gorlin  19 , Nicole E Brown  1 , Carolyn V Gould  1 , Kevin Berney  1 , Tina J Benoit  1 , Maureen J Miller  1 , Dane Freeman  20 , Deeksha Kartik  20 , Alicia M Fry  1 , Eduardo Azziz-Baumgartner  1 , Aron J Hall  1 , Adam MacNeil  1 , Adi V Gundlapalli  1 , Sridhar V Basavaraju  1 , Susan I Gerber  1 , Monica E Patton  1 , Brian Custer  2 , Phillip Williamson  4 , Graham Simmons  2 , Natalie J Thornburg  1 , Steven Kleinman  21 , Susan L Stramer  6 , Jean Opsomer  3 , Michael P Busch  2
Affiliations

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

Jefferson M Jones et al. JAMA. .

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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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.. Weighted SARS-CoV-2 Seroprevalence, US, July 2020-May 2021
Because the number of participating blood collection organizations increased, the number of blood donations included increased from 116 513 in July 2020 to 134 949 in May 2021 (see eTable 1 and eTable 5 in Supplement 1). Blood donations were collected from a catchment area representing 69% of the US population in July, increasing to 74% of the US population from October 2020 through May 2021. The solid black line illustrates the weighted spike antibody seroprevalence, representing the proportion of the population with antibodies from infection, vaccination, or both (combined seroprevalence). The dashed line illustrates the weighted seroprevalence of the population with both spike and nucleocapsid antibodies, representing the proportion of the population with antibodies from infection (infection-induced seroprevalence). Displayed error bars are 95% CIs. The x-axis tick marks indicate the middle of each month. For median specimen collection date each month, see eTable 5 in Supplement 1.
Figure 2.
Figure 2.. Weighted SARS-CoV-2 Seroprevalence by Study Region, US, January-May 2021
Maps display weighted seroprevalence by study region and month. On the left, spike and nucleocapsid antibody seroprevalence representing antibodies from infection. On the right, spike antibody seroprevalence representing antibodies from infection, vaccination, or both. The maps show the lower 48 states, the District of Columbia, Alaska, Hawaii, and Puerto Rico, and are Lambert Conformal projections that maintain direction, angle, and shape but not area or distance. See eTables 1 and 5 in Supplement 1, eTable 7 in Supplement 3, and eTable 8 in Supplement 4 for detailed data.
Figure 3.
Figure 3.. Weighted SARS-CoV-2 Seroprevalence by Census Region, Race and Ethnicity, Sex, and Age Group, US, July 2020-May 2021
Blood donations were collected from a catchment area representing 69% of the US population in July, increasing to 74% of the US population from October 2020 through May 2021. The solid lines illustrate the weighted spike antibody seroprevalence, representing the proportion of the population with antibodies from infection, vaccination, or both (combined seroprevalence). The dashed lines illustrate the weighted seroprevalence of the population with both spike and nucleocapsid antibodies, representing the proportion of the population with antibodies from infection (infection-induced seroprevalence). Displayed error bars are 95% CIs. All blood donor specimens missing race and ethnicity data were excluded except for specimens collected in the Puerto Rico study region, in which donor race and ethnicity data were not collected. The x-axis tick marks represent the middle of each month (range, 12th-15th day of each month). See eTables 1 and 5 in Supplement 1, eTable 7 in Supplement 3, and eTable 8 in Supplement 4 for detailed data. aThe monthly median number of blood donations was 8172 (25th-75th percentile [Q1-Q3], 7996-8223) for Hispanic persons, 3934 (Q1-Q3, 3758-3967) for non-Hispanic Asian persons, 3440 (Q1-Q3, 3187-3526) for non-Hispanic Black persons, and 114 172 (Q1-Q3, 110 818-114 910) for non-Hispanic White persons. bThe monthly median number of blood donations was 65 940 (Q1-Q3, 65 547-66 477) for males and 68 263 (Q1-Q3, 65 793-68 658) for females. cThe monthly median number of blood donations was 16 091 (Q1-Q3, 14 947-16 894) for people aged 16-29 years, 40 882 (Q1-Q3, 40 105-42 123) for people aged 30-49 years, 48 290 (Q1-Q3, 47 672-49 966) for people aged 50-64 years, and 26 798 (Q1-Q3, 26 160-27 496) for people aged ≥65 years.
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