Journal
JCI INSIGHT
Volume 6, Issue 8, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.146316
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Funding
- Mining for Miracles postdoctoral award from the British Columbia Children's Hospital (BCCH) Foundation
- BCCHRI Research Institute
- UBC Faculty of Medicine Summer Student Research Program Studentships
- UBC Four Year Fellowship
- BCCH Foundation through the Investigator Grant Award Program
- Michael Smith Foundation for Health Research
- BC Children's Hospital Foundation
- Intramural Research Program of the Vaccine Research Centre (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID), NIH
- Government of Canada
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Research suggests that most adults exhibit preexisting antibody cross-reactivity against SARS-CoV-2, involving spike protein among others. This finding supports further investigation into how this may impact the clinical severity of COVID-19 or SARS-CoV-2 vaccine responses.
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.
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