Abstract
BACKGROUNDEstimates of seroprevalence to SARS-CoV-2 vary widely and may influence vaccination response. We ascertained IgG levels across a single US metropolitan site, Chicago, from June 2020 through December 2020.METHODSParticipants (n = 7935) were recruited through electronic advertising and received materials for a self-sampled dried-blood spot assay through the mail or a minimal contact in-person method. IgG against the receptor-binding domain of SARS-CoV-2 was measured using an established highly sensitive and highly specific assay.RESULTSOverall seroprevalence was 17.9%, with no significant difference between method of contact. Only 2.5% of participants reported having had a diagnosis of COVID-19 based on virus detection, consistent with a 7-fold greater exposure to SARS-CoV-2 measured by serology than that detected by viral testing. The range of IgG level observed in seropositive participants from this community survey overlapped with the range of IgG levels associated with COVID-19 cases having a documented positive PCR test. From a subset of those who participated in repeat testing, half of seropositive individuals retained detectable antibodies for 3 to 4 months.CONCLUSIONQuantitative IgG measurements with a highly specific and sensitive assay indicated more widespread exposure to SARS-CoV-2 than observed by viral testing. The range of IgG concentrations produced from these asymptomatic exposures was similar to IgG levels occurring after documented nonhospitalized COVID-19, which were considerably lower than those produced from hospitalized COVID-19 cases. The differing ranges of IgG response, coupled with the rate of decay of antibodies, may influence response to subsequent viral exposure and vaccine.FundingNational Science Foundation grant 2035114, NIH grant 3UL1TR001422-06S4, NIH National Center for Advancing Translational Sciences grants UL1 TR001422 and UL1 TR002389, Dixon Family Foundation, Northwestern University Cancer Center (NIH grant P30 CA060553), and Walder Foundation’s Chicago Coronavirus Assessment Network.
Highlights
The presence of serum antibodies specific to SARS-CoV-2, the virus that causes COVID-19, reflects prior exposure
The range of IgG concentrations produced from these asymptomatic exposures was similar to IgG levels occurring after documented nonhospitalized COVID-19, which were considerably lower than those produced from hospitalized COVID-19 cases
The antigen in this assay is restricted to the receptor-binding domain (RBD), a small and specific domain within the SARS-CoV-2 spike protein; multiple studies have documented specificity of 97.7%–100% when using this target, owing to RBD’s limited sequence homology to other viruses [1, 15, 16]
Summary
The presence of serum antibodies specific to SARS-CoV-2, the virus that causes COVID-19, reflects prior exposure. We used DBS in an assay that indexes IgG levels to an antibody with known affinity to yield a concentration in micrograms per ml (μg/ml). The antigen in this assay is restricted to the receptor-binding domain (RBD), a small and specific domain within the SARS-CoV-2 spike protein; multiple studies have documented specificity of 97.7%–100% when using this target, owing to RBD’s limited sequence homology to other viruses [1, 15, 16]. Half of the participants were recruited from a wide socioeconomic range by zip codes These participants received and returned their DBS test kits through the US Postal Service. We ascertained IgG levels across a single US metropolitan site, Chicago, from June 2020 through December 2020
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