Journal Article

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

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

2021

Overview

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.

• Publisher: American Society for Clinical Investigation,American Society for Clinical investigation
• Subject: Adult / Antibodies / Antibodies, Neutralizing - blood / Antibodies, Neutralizing - immunology / Antibodies, Viral - blood / Antibodies, Viral - immunology / Antigens / Antigens, Viral - immunology / Asymptomatic / British Columbia - epidemiology / Competition / Coronaviridae / Coronaviruses / COVID-19 / COVID-19 - blood / COVID-19 - diagnosis / COVID-19 - immunology / COVID-19 - prevention & control / COVID-19 Serological Testing - statistics & numerical data / COVID-19 vaccines / COVID-19 Vaccines - administration & dosage / Cross Reactions - immunology / Cross-reactivity / Cross-Sectional Studies / Female / Geography / Healthy Volunteers / Humans / Immunity, Humoral / Immunoassay - statistics & numerical data / Immunology / Infections / Male / Middle Aged / Nucleocapsids / Peptide mapping / Peptides / Population / Prospective Studies / Proteins / SARS-CoV-2 - immunology / SARS-CoV-2 - isolation & purification / Severe acute respiratory syndrome coronavirus 2 / Severity of Illness Index / Spike protein