Serologic Cross-Reactivity of SARS-CoV-2 with Endemic and Seasonal Betacoronaviruses

J Clin Immunol. 2021 Jul;41(5):906-913. doi: 10.1007/s10875-021-00997-6. Epub 2021 Mar 16.


In order to properly understand the spread of SARS-CoV-2 infection and development of humoral immunity, researchers have evaluated the presence of serum antibodies of people worldwide experiencing the pandemic. These studies rely on the use of recombinant proteins from the viral genome in order to identify serum antibodies that recognize SARS-CoV-2 epitopes. Here, we discuss the cross-reactivity potential of SARS-CoV-2 antibodies with the full spike proteins of four other betacoronaviruses that cause disease in humans, MERS-CoV, SARS-CoV, HCoV-OC43, and HCoV-HKU1. Using enzyme-linked immunosorbent assays (ELISAs), we detected the potential cross-reactivity of antibodies against SARS-CoV-2 towards the four other coronaviruses, with the strongest cross-recognition between SARS-CoV-2 and SARS /MERS-CoV antibodies, as expected based on sequence homology of their respective spike proteins. Further analysis of cross-reactivity could provide informative data that could lead to intelligently designed pan-coronavirus therapeutics or vaccines.

Keywords: Coronavirus; Infectious disease; Serology.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood
  • Betacoronavirus / immunology*
  • Cross Reactions
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Middle Aged
  • SARS-CoV-2 / immunology*
  • Sequence Homology, Amino Acid
  • Spike Glycoprotein, Coronavirus / immunology
  • Young Adult


  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus