A majority of uninfected adults show preexisting antibody reactivity against SARS-CoV-2 Academic Article uri icon

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  • 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.


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

publication date

  • April 22, 2021