Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity

Cell. 2020 Nov 12;183(4):996-1012.e19. doi: 10.1016/j.cell.2020.09.038. Epub 2020 Sep 16.

Abstract

Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4+ and CD8+ T cells were each associated with milder disease. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4+ and CD8+ T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals ≥ 65 years old. Scarcity of naive T cells was also associated with aging and poor disease outcomes. A parsimonious explanation is that coordinated CD4+ T cell, CD8+ T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between aging and impaired adaptive immune responses to SARS-CoV-2.

Keywords: CD4; CD8; CXCL10; IP-10; Spike; T cells; adaptive immunity; antibody; coronavirus; epitopes; neutralizing antibodies.

Publication types

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

MeSH terms

  • Acute Disease
  • Adaptive Immunity*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Antigens, Viral / immunology*
  • Betacoronavirus / immunology
  • Betacoronavirus / isolation & purification
  • Betacoronavirus / metabolism
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Coronavirus Infections / immunology
  • Coronavirus Infections / pathology*
  • Coronavirus Infections / virology
  • Cytokines / blood
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / pathology*
  • Pneumonia, Viral / virology
  • Severity of Illness Index
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Cytokines

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2