Mapping a Pandemic: SARS-CoV-2 Seropositivity in the United States

16.8 million SARS-CoV-2 infections in the US went undiagnosed in the first 6 months of the pandemic compared to 3.5 million diagnosed infections.
Elucidating seroprevalence in COVID-19 Symptoms of SARS-CoV-2 infection range from completely asymptomatic, to those of a common cold, to a drop in oxygen saturation and lung function, and death in some patients. To evaluate the proportion of the U.S. population who had an undiagnosed infection during the first wave of the COVID-19 pandemic, we measured antibody prevalence in study participants who had not previously been diagnosed with a SARS-CoV-2 infection. By mid-July of 2020, 16.8 million people had an undiagnosed SARS-CoV-2 infection, almost five times the rate of diagnosed infections.
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.