COVID novel? likely not: In Vancouver, Canada in early 2020, a majority (more than 90%) of uninfected adults showed preexisting antibody reactivity against SARS-CoV-2

by Paul Alexander

determined that more than 90% of uninfected adults had antibody reactivity against spike protein, receptor-binding domain (RBD), N-terminal domain (NTD), or nucleocapsid (N) protein from SARS-CoV-2


Key findings:

  • About 1500 people in study had full symptoms of COVID-19, and about 75% of these participants first reported these symptoms in December 2019 and January-March in 2020.

  • Interestingly, the nucleocapsid protein of SARS-CoV-2, which is commonly targeted in other serological tests to monitor natural immunity, was often found to not elicit antibodies in confirmed COVID-19 cases.

  • Over 90% of the participants in the first SARS-CoV-2 antibody testing study had detectable antibodies against different proteins in SARS-CoV-2, which indicated a much higher level of infection of Canadians with the virus and higher antibody levels than previously reported.

“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.”