SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19

Nature. 2020 Nov;587(7833):270-274. doi: 10.1038/s41586-020-2598-9. Epub 2020 Jul 29.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic1,2. Clinical manifestations of COVID-19 vary, ranging from asymptomatic infection to respiratory failure. The mechanisms that determine such variable outcomes remain unresolved. Here we investigated CD4+ T cells that are reactive against the spike glycoprotein of SARS-CoV-2 in the peripheral blood of patients with COVID-19 and SARS-CoV-2-unexposed healthy donors. We detected spike-reactive CD4+ T cells not only in 83% of patients with COVID-19 but also in 35% of healthy donors. Spike-reactive CD4+ T cells in healthy donors were primarily active against C-terminal epitopes in the spike protein, which show a higher homology to spike glycoproteins of human endemic coronaviruses, compared with N-terminal epitopes. Spike-protein-reactive T cell lines generated from SARS-CoV-2-naive healthy donors responded similarly to the C-terminal region of the spike proteins of the human endemic coronaviruses 229E and OC43, as well as that of SARS-CoV-2. This results indicate that spike-protein cross-reactive T cells are present, which were probably generated during previous encounters with endemic coronaviruses. The effect of pre-existing SARS-CoV-2 cross-reactive T cells on clinical outcomes remains to be determined in larger cohorts. However, the presence of spike-protein cross-reactive T cells in a considerable fraction of the general population may affect the dynamics of the current pandemic, and has important implications for the design and analysis of upcoming trials investigating COVID-19 vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Betacoronavirus / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Coronavirus 229E, Human / immunology
  • Coronavirus Infections / immunology*
  • Coronavirus NL63, Human / immunology
  • Coronavirus OC43, Human / immunology
  • Cross Reactions
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Healthy Volunteers
  • Humans
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / immunology*
  • Spike Glycoprotein, Coronavirus / immunology*

Substances

  • Epitopes, T-Lymphocyte
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2