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Seroprevalence of Antibodies to SARS-CoV-2 in 10 Sites in the United States, March 23-May 12, 2020

Educational Objective
To estimate prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in convenience samples from several geographic sites in the US.
1 Credit CME
Key Points

Question  What proportion of persons in 10 US sites had detectable antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 23 to May 12, 2020?

Findings  In this cross-sectional study of 16 025 residual clinical specimens, estimates of the proportion of persons with detectable SARS-CoV-2 antibodies ranged from 1.0% in the San Francisco Bay area (collected April 23-27) to 6.9% of persons in New York City (collected March 23-April 1). Six to 24 times more infections were estimated per site with seroprevalence than with coronavirus disease 2019 (COVID-19) case report data.

Meaning  For most sites, it is likely that greater than 10 times more SARS-CoV-2 infections occurred than the number of reported COVID-19 cases; most persons in each site, however, likely had no detectable SARS-CoV-2 antibodies.

Abstract

Importance  Reported cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely underestimate the prevalence of infection in affected communities. Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected.

Objective  To estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the US.

Design, Setting, and Participants  This cross-sectional study performed serologic testing on a convenience sample of residual sera obtained from persons of all ages. The serum was collected from March 23 through May 12, 2020, for routine clinical testing by 2 commercial laboratory companies. Sites of collection were San Francisco Bay area, California; Connecticut; south Florida; Louisiana; Minneapolis-St Paul-St Cloud metro area, Minnesota; Missouri; New York City metro area, New York; Philadelphia metro area, Pennsylvania; Utah; and western Washington State.

Exposures  Infection with SARS-CoV-2.

Main Outcomes and Measures  The presence of antibodies to SARS-CoV-2 spike protein was estimated using an enzyme-linked immunosorbent assay, and estimates were standardized to the site populations by age and sex. Estimates were adjusted for test performance characteristics (96.0% sensitivity and 99.3% specificity). The number of infections in each site was estimated by extrapolating seroprevalence to site populations; estimated infections were compared with the number of reported coronavirus disease 2019 (COVID-19) cases as of last specimen collection date.

Results  Serum samples were tested from 16 025 persons, 8853 (55.2%) of whom were women; 1205 (7.5%) were 18 years or younger and 5845 (36.2%) were 65 years or older. Most specimens from each site had no evidence of antibodies to SARS-CoV-2. Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein antibodies ranged from 1.0% in the San Francisco Bay area (collected April 23-27) to 6.9% of persons in New York City (collected March 23-April 1). The estimated number of infections ranged from 6 to 24 times the number of reported cases; for 7 sites (Connecticut, Florida, Louisiana, Missouri, New York City metro area, Utah, and western Washington State), an estimated greater than 10 times more SARS-CoV-2 infections occurred than the number of reported cases.

Conclusions and Relevance  During March to early May 2020, most persons in 10 diverse geographic sites in the US had not been infected with SARS-CoV-2 virus. The estimated number of infections, however, was much greater than the number of reported cases in all sites. The findings may reflect the number of persons who had mild or no illness or who did not seek medical care or undergo testing but who still may have contributed to ongoing virus transmission in the population.

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: July 7, 2020.

Corresponding Author: Fiona P. Havers, MD, MHS, CDC COVID-19 Response Team, Centers for Disease Control and Prevention, 1600 Clifton Rd, MS H24-6, Atlanta, GA 30329 (fhavers@cdc.gov).

Published Online: July 21, 2020. doi:10.1001/jamainternmed.2020.4130

Author Contributions: Drs Havers and Lim had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Havers, Reed, Lim, Hall, Fry, Owen, Blackmore, Blog, Lindquist, Turabelidze, Wiesman, Schiffer, Thornburg.

Acquisition, analysis, or interpretation of data: Havers, Reed, Lim, Montgomery, Klena, Cannon, Chiang, Gibbons, Krapiunaya, Morales-Betoulle, Roguski, Rasheed, Freeman, Lester, Mills, Carroll, Owen, Johnson, Semenova, Blog, Chai, Dunn, Hand, Jain, Lynfield, Pritchard, Sokol, Sosa, Watkins, Williams, Yendell, Schiffer, Thornburg.

Drafting of the manuscript: Havers, Lim, Klena, Fry, Thornburg.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Havers, Lim, Gibbons, Roguski, Schiffer.

Obtained funding: Havers.

Administrative, technical, or material support: Havers, Montgomery, Klena, Cannon, Chiang, Morales-Betoulle, Mills, Carroll, Owen, Johnson, Semenova, Blackmore, Blog, Chai, Dunn, Jain, Lindquist, Pritchard, Sokol, Sosa, Turabelidze, Watkins, Wiesman, Williams, Schiffer, Thornburg.

Study supervision: Havers, Reed, Montgomery, Hall, Fry, Johnson, Blog, Pritchard, Schiffer, Thornburg.

Conflict of Interest Disclosures: Dr Wiesman reported receiving grants from US Department of Health and Human Services during the conduct of the study. No other disclosures were reported.

Funding/Support: This work was supported by the Centers for Disease Control and Prevention, Atlanta, Georgia.

Role of the Funder/Sponsor: The Centers for Disease Control and Prevention was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The author members of the CDC COVID-19 Response Team are Drs Havers, Reed, Lim, Montgomery, Klena, Hall, Fry, Chiang, Morales-Betoulle, Rasheed, Freeman, Lester, Mills, Carroll, Owen, Johnson, Semenova, and Thornburg; Mses Cannon, Gibbons, Krapiunaya, and Roguski; and Mr Schiffer. The author members of the State Collaborator Group are Drs Blackmore, Blog, Chai, Dunn, Jain, Lindquist, Lynfield, Sosa, Turabelidze, Watkins, Wiesman, Williams, and Yendell; Mses Hand and Sokol; and Mr Pritchard.

Disclaimer: The findings and conclusions in the article are those of the authors and do not necessarily represent the views of the US Centers for Disease Control and Prevention.

Additional Contributions: We thank LabCorp and Quest for supplying specimens. From Quest: William A. Meyer III, PhD, Larry A. Hirsch, BS, Taylor Hwang, BS, and Janet M. Rochat, MS. From the New York City Department of Mental Health and Hygiene: Marcelle Layton, MD. From the Centers for Disease Control and Prevention Molecular Pathogenesis and Immunology Research Laboratory team: Bailey Alston, MS, Muyiwa Ategbole, MPH, Shanna Bolcen, MSPH, Darbi Boulay, BS, Peter Browning, BS, Li Cronin, MS, Ebenezer David, PhD, Rita Desai, BS, Monica Epperson, PhD, Yamini Gorantla, PhD, Lily Jia, MS, Han Li, PhD, Pete Maniatis, MS, Jeff Martin, BA, Kimberly Moss, BS, Kristina Ortiz, MS, Palak Patel, MS, So Hee Park, BS, Yunlong Qin, PhD, Evelene Steward-Clark, MS, Heather Tatum, BS, Andrew Vogan, MS, and Briana Zellner, PhD. We also thank Ian E. Fellows, PhD, of Fellows Statistics for input on statistical methodology. These individuals were not compensated directly by CDC for their participation in this specific study.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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