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JCI Insight . A majority of uninfected adults show pre-existing antibody reactivity against SARS-CoV-2

tetano

Editor, Senior Moderator
JCI Insight


. 2021 Mar 15;146316.
doi: 10.1172/jci.insight.146316. Online ahead of print.
A majority of uninfected adults show pre-existing antibody reactivity against SARS-CoV-2


Abdelilah Majdoubi[SUP] 1 [/SUP], Christina Michalski[SUP] 1 [/SUP], Sarah E O'Connell[SUP] 2 [/SUP], Sarah Dada[SUP] 1 [/SUP], Sandeep R Narpala[SUP] 2 [/SUP], Jean P Gelinas[SUP] 3 [/SUP], Disha Mehta[SUP] 3 [/SUP], Claire Cheung[SUP] 1 [/SUP], Dirk Fh Winkler[SUP] 4 [/SUP], Manjula Basappa[SUP] 2 [/SUP], Aaron C Liu[SUP] 1 [/SUP], Matthias G?rges[SUP] 5 [/SUP], Vilte E Barakauskas[SUP] 6 [/SUP], Michael A Irvine[SUP] 7 [/SUP], Jennifer Mehalko[SUP] 8 [/SUP], Dominic Esposito[SUP] 8 [/SUP], Inna Sekirov[SUP] 9 [/SUP], Agatha N Jassem[SUP] 9 [/SUP], David M Goldfarb[SUP] 1 [/SUP], Steven Pelech[SUP] 4 [/SUP], Daniel C Douek[SUP] 2 [/SUP], Adrian B McDermott[SUP] 2 [/SUP], Pascal M Lavoie[SUP] 1 [/SUP]



Affiliations

Abstract

Pre-existing cross-reactivity to SARS-CoV-2 may occur in 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 ~0.6% of non-triaged adults from the greater Vancouver area, Canada between May 17th and June 19th 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 determine that more than 90% of uninfected adults showed antibody reactivity against the spike, receptor-binding domain (RBD), N-terminal domains (NTD) or the nucleocapsid (N) protein from SARS-CoV-2. This sero-reactivity 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 non-structural viral proteins. We conclude that most adults display pre-existing 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.

Keywords: Adaptive immunity; COVID-19; Immunology.
 
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