Antibody reactivity to SARS-CoV-2 in adults from the Vancouver metropolitan area, Canada

Majdoubi, Abdelilah; Michalski, Christina; O039, Sarah E; Connell,; Dada, Sarah; Narpala, Sandeep; Gelinas, Jean; Mehta, Disha; Cheung, Claire; Basappa, Manjula; Liu, Aaron C; Gorges, Matthias; Barakauskas, Vilte E; Mehalko, Jennifer; Esposito, Dominic; Sekirov, Inna; Jassem, Agatha N; Goldfarb, David M; Douek, Daniel C; McDermott, Adrian B; Lavoie, Pascal M

BackgroundPre-existing antibody reactivity against SARS-CoV-2 in unexposed people is a potentially important consideration for COVID-19 severity and vaccine responses. However, it has been difficult to quantify due to a lack of reliable defined background titers in unexposed individuals. MethodsWe measured IgG against multiple SARS-CoV-2 antigens, SARS-CoV and other circulating coronavirus spike proteins using a highly sensitive multiplex assay, and total SARS-CoV-2 spike-specific antibodies (IgG/M/A) using a commercial CLIA assay in 276 adults from the Vancouver area, Canada between May 17th and June 19th 2020. Reactivity threshold in unexposed individuals were defined comparing to pre-pandemic sera and to sera from infants under 6 months of age. ResultsThe seroprevalence from a SARS-CoV-2 exposure, adjusted for false-positive and false-negative test results, was 0.60% in our adult cohort. High antibody reactivity to circulating endemic coronaviruses was observed in all adults and was [~]10-fold lower in infants <6 months. Consistent with a waning of maternal antibodies, reactivity in infants decreased more than 50-fold [~]8 months later. SARS-CoV-2 Spike, RBD, NTD or nucleocapsid antibody reactivity >100-fold above that of older infants was detected in the vast majority of unexposed adults and pre-pandemic sera. This antibody reactivity correlated with titers against circulating coronaviruses, but not with age, sex, or whether adults were healthcare workers. ConclusionA majority of unexposed adults have pre-existing antibody reactivity against SARS-CoV-2. The lack of similar antibody reactivity in infants where maternal antibodies have waned suggests that this cross-reactivity is acquired, likely from repeated exposures to circulating coronaviruses. FundingBC Childrens Hospital Foundation, NIH/NIAID