Immunological imprinting of the antibody response in COVID-19 patients

Nat Commun. 2021 Jun 18;12(1):3781. doi: 10.1038/s41467-021-23977-1.


In addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.

Publication types

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

MeSH terms

  • Aged
  • Antibodies, Viral / blood*
  • Antibodies, Viral / immunology
  • Antibody Formation
  • COVID-19 / blood
  • COVID-19 / immunology*
  • COVID-19 / transmission
  • COVID-19 / virology
  • Cross Reactions
  • Female
  • Humans
  • Male
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / pathogenicity
  • Spike Glycoprotein, Coronavirus / immunology*


  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2