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Undiagnosed SARS-CoV-2 seropositivity during the first 6 months of the COVID-19 pandemic in the United States

Science Translational Medicine2021Vol. 13(601)

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Heather Kalish, Carleen Klumpp‐Thomas, Sally Hunsberger, Holly Ann Baus, Michael P. Fay, Nalyn Siripong, Jing Wang, Jennifer Hicks, Jennifer Mehalko, Jameson Travers, Matthew Drew, Kyle Pauly, Jacquelyn Spathies, Tran B. Ngo, Kenneth M. Adusei, Maria Karkanitsa, Jennifer A. Croker, Yan Li, Barry I. Graubard, Lindsay Czajkowski, Olivia Belliveau, Cheryl Chairez, Kelly Snead, Peter Frank, Anandakumar Shunmugavel, Alison Han, Luca T. Giurgea, Luz Angela Rosas, Rachel Bean, Rani Athota, Adriana Cervantes-Medina, Monica Gouzoulis, Brittany Heffelfinger, Shannon Valenti, Rocco Caldararo, Michelle M. Kolberg, Andrew P. Kelly, Reid Simon, Saifullah Shafiq, Vanessa Wall, Susan Reed, Eric W. Ford, Ravi Lokwani, John-Paul Denson, Simon Messing, Sam Michael, William Gillette, Robert P. Kimberly, Steven E. Reís, Matthew D. Hall, Dominic Esposito, Matthew J. Memoli, Kaitlyn Sadtler

Abstract

Asymptomatic SARS-CoV-2 infection and delayed implementation of diagnostics have led to poorly defined viral prevalence rates in the United States and elsewhere. To address this, we analyzed seropositivity in 9089 adults in the United States who had not been diagnosed previously with COVID-19. Individuals with characteristics that reflected the U.S. population (n = 27,716) were selected by quota sampling from 462,949 volunteers. Enrolled participants (n = 11,382) provided medical, geographic, demographic, and socioeconomic information and dried blood samples. Survey questions coincident with the Behavioral Risk Factor Surveillance System survey, a large probability-based national survey, were used to adjust for selection bias. Most blood samples (88.7%) were collected between 10 May and 31 July 2020 and were processed using ELISA to measure seropositivity (IgG and IgM antibodies against SARS-CoV-2 spike protein and the spike protein receptor binding domain). The overall weighted undiagnosed seropositivity estimate was 4.6% (95% CI, 2.6 to 6.5%), with race, age, sex, ethnicity, and urban/rural subgroup estimates ranging from 1.1% to 14.2%. The highest seropositivity estimates were in African American participants; younger, female, and Hispanic participants; and residents of urban centers. These data indicate that there were 4.8 undiagnosed SARS-CoV-2 infections for every diagnosed case of COVID-19, and an estimated 16.8 million infections were undiagnosed by mid-July 2020 in the United States.

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Abstract

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