Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection

Cell. 2021 Apr 1;184(7):1858-1864.e10. doi: 10.1016/j.cell.2021.02.010. Epub 2021 Feb 9.


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread within the human population. Although SARS-CoV-2 is a novel coronavirus, most humans had been previously exposed to other antigenically distinct common seasonal human coronaviruses (hCoVs) before the coronavirus disease 2019 (COVID-19) pandemic. Here, we quantified levels of SARS-CoV-2-reactive antibodies and hCoV-reactive antibodies in serum samples collected from 431 humans before the COVID-19 pandemic. We then quantified pre-pandemic antibody levels in serum from a separate cohort of 251 individuals who became PCR-confirmed infected with SARS-CoV-2. Finally, we longitudinally measured hCoV and SARS-CoV-2 antibodies in the serum of hospitalized COVID-19 patients. Our studies indicate that most individuals possessed hCoV-reactive antibodies before the COVID-19 pandemic. We determined that ∼20% of these individuals possessed non-neutralizing antibodies that cross-reacted with SARS-CoV-2 spike and nucleocapsid proteins. These antibodies were not associated with protection against SARS-CoV-2 infections or hospitalizations, but they were boosted upon SARS-CoV-2 infection.

Keywords: SARS-CoV-2; antibodies; coronavirus; pre-existing immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alphacoronavirus / immunology*
  • Animals
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • Betacoronavirus / immunology*
  • COVID-19 / immunology*
  • COVID-19 Serological Testing
  • Child
  • Child, Preschool
  • Chlorocebus aethiops
  • Cross Protection
  • Cross Reactions
  • Disease Susceptibility
  • HEK293 Cells
  • Humans
  • Infant
  • Infant, Newborn
  • Vero Cells


  • Antibodies, Viral