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Abstract
Preexisting cross-reactivity to SARS-CoV-2 occurs in the absence of prior viral exposure. However, this has been difficult to quantify at the population level due to a lack of reliably defined seroreactivity thresholds. Using an orthogonal antibody testing approach, we estimated that about 0.6% of nontriaged adults from the greater Vancouver, Canada, area between May 17 and June 19, 2020, showed clear evidence of a prior SARS-CoV-2 infection, after adjusting for false-positive and false-negative test results. Using a highly sensitive multiplex assay and positive/negative thresholds established in infants in whom maternal antibodies have waned, we determined that more than 90% of uninfected adults showed antibody reactivity against the spike protein, receptor-binding domain (RBD), N-terminal domain (NTD), or the nucleocapsid (N) protein from SARS-CoV-2. This seroreactivity was evenly distributed across age and sex, correlated with circulating coronaviruses’ reactivity, and was partially outcompeted by soluble circulating coronaviruses’ spike. Using a custom SARS-CoV-2 peptide mapping array, we found that this antibody reactivity broadly mapped to spike and to conserved nonstructural viral proteins. We conclude that most adults display preexisting antibody cross-reactivity against SARS-CoV-2, which further supports investigation of how this may impact the clinical severity of COVID-19 or SARS-CoV-2 vaccine responses.
Highlights
Coronavirus disease 2019 (COVID-19) was declared a global pandemic on March 11, 2020, and has resulted in almost 100 million confirmed cases and 2.1 million deaths worldwide as of January 24, 2020
This prevalence of SARS-CoV-2 infections was identical to the 0.55% prevalence reported by the British Columbia (BC) CDC on 885 residual sera obtained from an outpatient laboratory network in the Lower Mainland of BC between May 15 and May 27, 2020
The current study confirms that COVID-19 transmission in BC after the first wave was low, even among healthcare workers (HCW), contrasting with a high seroprevalence reported among HCW in other studies [13,14,15], which may be attributed to the very low number of total tested cases in BC during the first wave
Summary
Coronavirus disease 2019 (COVID-19) was declared a global pandemic on March 11, 2020, and has resulted in almost 100 million confirmed cases and 2.1 million deaths worldwide as of January 24, 2020. While much attention has focused on defining immune reactivity in individuals after infection, other data indicate that many individuals show preexisting SARSCoV-2 cross-reactive T and B cells without prior exposure to the virus [3,4,5]. The extent of preexisting SARS-CoV-2 antibody reactivity at the population level has been difficult to estimate, due to a lack of assay sensitivity [6] and clearly definable background thresholds to identify meaningful seroreactivity among individuals who have been unexposed to the virus [7]. The common occurrence of circulating coronaviruses year after year and their structural similarity with SARS-CoV-2 raises the possibility that the former may stimulate cross-reactive responses toward SARS-CoV-2 and that this heterotopic immunity may impact clinical susceptibility to COVID-19 and/or modulate responses to the SARS-CoV-2 vaccine [10, 11]
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