Transient and durable T cell reactivity after COVID-19

Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2203659119. doi: 10.1073/pnas.2203659119. Epub 2022 Jul 12.


This study analyzed whole blood samples (n = 56) retrieved from 30 patients at 1 to 21 (median 9) mo after verified COVID-19 to determine the polarity and duration of antigen-specific T cell reactivity against severe acute respiratory syndrome coronavirus 2-derived antigens. Multimeric peptides spanning the entire nucleocapsid protein triggered strikingly synchronous formation of interleukin (IL)-4, IL-12, IL-13, and IL-17 ex vivo until ∼70 d after confirmed infection, whereafter this reactivity was no longer inducible. In contrast, levels of nucleocapsid-induced IL-2 and interferon-γ remained stable and highly correlated at 3 to 21 mo after infection. Similar cytokine dynamics were observed in unvaccinated, convalescent patients using whole-blood samples stimulated with peptides spanning the N-terminal portion of the spike 1 protein. These results unravel two phases of T cell reactivity following natural COVID-19: an early, synchronous response indicating transient presence of multipolar, antigen-specific T helper (TH) cells followed by an equally synchronous and durable TH1-like reactivity reflecting long-lasting T cell memory.

Keywords: COVID-19; SARS-CoV-2; T cell cytokines; T helper cells; longevity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral / blood
  • Antigens, Viral / immunology
  • COVID-19* / blood
  • COVID-19* / immunology
  • Convalescence
  • Cytokines* / blood
  • Humans
  • Interferon-gamma / blood
  • Nucleocapsid Proteins / immunology
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus / immunology
  • T-Lymphocytes, Helper-Inducer* / immunology


  • Antibodies, Viral
  • Antigens, Viral
  • Cytokines
  • Nucleocapsid Proteins
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Interferon-gamma