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A majority of uninfected adults show preexisting antibody reactivity against SARS-CoV-2
Abdelilah Majdoubi, … , Adrian B. McDermott, Pascal M. Lavoie
Abdelilah Majdoubi, … , Adrian B. McDermott, Pascal M. Lavoie
Published March 15, 2021
Citation Information: JCI Insight. 2021;6(8):e146316. https://doi.org/10.1172/jci.insight.146316.
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Research Article COVID-19 Immunology

A majority of uninfected adults show preexisting antibody reactivity against SARS-CoV-2

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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.

Authors

Abdelilah Majdoubi, Christina Michalski, Sarah E. O’Connell, Sarah Dada, Sandeep Narpala, Jean Gelinas, Disha Mehta, Claire Cheung, Dirk F.H. Winkler, Manjula Basappa, Aaron C. Liu, Matthias Görges, Vilte E. Barakauskas, Mike Irvine, Jennifer Mehalko, Dominic Esposito, Inna Sekirov, Agatha N. Jassem, David M. Goldfarb, Steven Pelech, Daniel C. Douek, Adrian B. McDermott, Pascal M. Lavoie

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Figure 1

Hierarchical clustering of individual based on serum SARS-CoV-2 antibody reactivity profiles.

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Hierarchical clustering of individual based on serum SARS-CoV-2 antibody...
COVID-19 diagnosis identifies convalescing individuals who had a positive viral test by PCR. This figure combines data from 276 study participants plus the 5 COVID-19 convalescent control sera. Color scale represents antibody reactivity as a Z score.

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