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

Abstract

Asymptomatic SARS-CoV-2 infection and delayed implementation of diagnostics have led to poorly defined viral prevalence rates. To address this, we analyzed seropositivity in US adults who have not previously been diagnosed with COVID-19. Individuals with characteristics that reflect the US population (n = 11,382) and who had not previously been diagnosed with COVID-19 were selected by quota sampling from 241,424 volunteers (ClinicalTrials.govNCT04334954). Enrolled participants provided medical, geographic, demographic, and socioeconomic information and 9,028 blood samples. The majority (88.7%) of samples were collected between May 10th and July 31st, 2020. Samples were analyzed via ELISA for anti-Spike and anti-RBD antibodies. Estimation of seroprevalence was performed by using a weighted analysis to reflect the US population. We detected an undiagnosed seropositivity rate of 4.6% (95% CI: 2.6 – 6.5%). There was distinct regional variability, with heightened seropositivity in locations of early outbreaks. Subgroup analysis demonstrated that the highest estimated undiagnosed seropositivity within groups was detected in younger participants (ages 18-45, 5.9%), females (5.5%), Black/African American (14.2%), Hispanic (6.1%), and Urban residents (5.3%), and lower undiagnosed seropositivity in those with chronic diseases. During the first wave of infection over the spring/summer of 2020 an estimate of 4.6% of adults had a prior undiagnosed SARS-CoV-2 infection. These data indicate that there were 4.8 (95% CI: 2.8-6.8) undiagnosed cases for every diagnosed case of COVID-19 during this same time period in the United States, and an estimated 16.8 million undiagnosed cases by mid-July 2020.

Antigen-based multiplex strategies to discriminate SARS-CoV-2 natural and vaccine induced immunity from seasonal human coronavirus humoral responses

“…A native-like SARS-CoV-2 prefusion stabilized S-2P glycoprotein ectodomain trimer (hereafter referred to as spike) (8,9) has been adopted for large-scale SARS-CoV-2 antigenbased serology and serosurveillance (10)(11)(12)(13). The receptor-binding domain (RBD) located within the more variable S1 subunit of the S glycoprotein, lacking potentially conserved epitopes with endemic seasonal human coronavirus (HCoV) S glycoproteins and conferring specificity for SARS-CoV-2, has also been extensively used in antigen-based immunoassays (10,(14)(15)(16).…”

SARS-CoV-2 incidence and risk factors in a national, community-based prospective cohort of U.S. adults

“…3 One recent study in a nationally representative sample of U.S. adults found that 4.6% had a history of undiagnosed SARS-CoV-2 as of July 2020: about 5 undiagnosed infections for every diagnosed case. 4…”

“…A major challenge of controlling community transmission of SARS-CoV-2 is that the virus’ infectious period allows for onward spread prior to recognition of infection, by the substantial proportion of people with asymptomatic infection, and during the pre-symptomatic period among those who go on to develop symptoms. 4, 5…”

Vaccination Planning under Uncertainty, with Application to Covid-19

“…Epidemiologists have conjectured a wide range of possibilities for the degree to which confirmed cases undercount actual cases. A plausible possibility is that the actual number of cases is five times the number of confirmed cases (Kalish et al, 2021), which implies that the actual cumulative number of cases is about 89.5 million. The size of the American population is about 331 million.…”

“…Confirmed cases undercount actual cases to an unknown degree. A plausible possibility is that the actual number of cases was five times the number of confirmed cases(Kalish et al, 2021). If so, the actual number of new cases per day was 1,080,350.…”