Early cross-coronavirus reactive signatures of humoral immunity against COVID-19

Sci Immunol. 2021 Oct 15;6(64):eabj2901. doi: 10.1126/sciimmunol.abj2901. Epub 2021 Oct 15.


The introduction of vaccines has inspired hope in the battle against SARS-CoV-2. However, the emergence of viral variants, in the absence of potent antivirals, has left the world struggling with the uncertain nature of this disease. Antibodies currently represent the strongest correlate of immunity against SARS-CoV-2, thus we profiled the earliest humoral signatures in a large cohort of acutely ill (survivors and nonsurvivors) and mild or asymptomatic individuals with COVID-19. Although a SARS-CoV-2–specific immune response evolved rapidly in survivors of COVID-19, nonsurvivors exhibited blunted and delayed humoral immune evolution, particularly with respect to S2-specific antibodies. Given the conservation of S2 across β-coronaviruses, we found that the early development of SARS-CoV-2–specific immunity occurred in tandem with preexisting common β-coronavirus OC43 humoral immunity in survivors, which was also selectively expanded in individuals that develop a paucisymptomatic infection. These data point to the importance of cross-coronavirus immunity as a correlate of protection against COVID-19.

Publication types

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

MeSH terms

  • Adolescent
  • COVID-19 / immunology*
  • Cohort Studies
  • Coronavirus OC43, Human / immunology
  • Cross Reactions*
  • Disease Progression
  • Humans
  • Immunity, Humoral*
  • Immunoglobulin Class Switching
  • Receptors, Fc / immunology
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / immunology
  • Survivors
  • Young Adult


  • Receptors, Fc
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2