Longitudinal antibody repertoire in "mild" versus "severe" COVID-19 patients reveals immune markers associated with disease severity and resolution

Sci Adv. 2021 Mar 5;7(10):eabf2467. doi: 10.1126/sciadv.abf2467. Print 2021 Mar.


Limited knowledge exists on immune markers associated with disease severity or recovery in patients with coronavirus disease 2019 (COVID-19). Here, we elucidated longitudinal evolution of SARS-CoV-2 antibody repertoire in patients with acute COVID-19. Differential kinetics was observed for immunoglobulin M (IgM)/IgG/IgA epitope diversity, antibody binding, and affinity maturation in "severe" versus "mild" COVID-19 patients. IgG profile demonstrated immunodominant antigenic sequences encompassing fusion peptide and receptor binding domain (RBD) in patients with mild COVID-19 who recovered early compared with "fatal" COVID-19 patients. In patients with severe COVID-19, high-titer IgA were observed, primarily against RBD, especially in patients who succumbed to SARS-CoV-2 infection. The patients with mild COVID-19 showed marked increase in antibody affinity maturation to prefusion SARS-CoV-2 spike that associated with faster recovery from COVID-19. This study revealed antibody markers associated with disease severity and resolution of clinical disease that could inform development and evaluation of effective immune-based countermeasures against COVID-19.

Publication types

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

MeSH terms

  • Antibodies, Viral / blood*
  • Antibodies, Viral / immunology*
  • Antibody Affinity / immunology
  • Antibody Formation / immunology
  • Antigens, Viral / immunology*
  • Biomarkers / blood*
  • COVID-19 / blood
  • COVID-19 / immunology*
  • COVID-19 / pathology*
  • COVID-19 / virology
  • Cytokines / blood
  • HEK293 Cells
  • Hospitalization
  • Humans
  • Immunoglobulin Class Switching
  • Kinetics
  • Neutralization Tests
  • Protein Binding
  • Protein Domains
  • SARS-CoV-2 / physiology*
  • Severity of Illness Index*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology
  • Viral Load


  • Antibodies, Viral
  • Antigens, Viral
  • Biomarkers
  • Cytokines
  • Spike Glycoprotein, Coronavirus