SARS-CoV-2-reactive interferon-γ-producing CD8+ T cells in patients hospitalized with coronavirus disease 2019

J Med Virol. 2021 Jan;93(1):375-382. doi: 10.1002/jmv.26213. Epub 2020 Jul 2.

Abstract

There is limited information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T-cell immune responses in patients with coronavirus disease 2019 (COVID-19). Both CD4+ and CD8+ T cells may be instrumental in resolution of and protection from SARS-CoV-2 infection. Here, we tested 25 hospitalized patients either with microbiologically documented COVID-19 (n = 19) or highly suspected of having the disease (n = 6) for presence of SARS-CoV-2-reactive CD69+ expressing interferon-γ (IFN-γ) producing CD8+ T cells using flow-cytometry for intracellular cytokine staining assay. Two sets of overlapping peptides encompassing the SARS-CoV-2 Spike glycoprotein N-terminal 1 to 643 amino acid sequence and the entire sequence of SARS-CoV-2 M protein were used simultaneously as antigenic stimulus. Ten patients (40%) had detectable responses, displaying frequencies ranging from 0.15 to 2.7% (median of 0.57 cells/µL; range, 0.43-9.98 cells/µL). The detection rate of SARS-CoV-2-reactive IFN-γ CD8+ T cells in patients admitted to intensive care was comparable (P = .28) to the rate in patients hospitalized in other medical wards. No correlation was found between SARS-CoV-2-reactive IFN-γ CD8+ T-cell counts and SARS-CoV-2 S-specific antibody levels. Likewise, no correlation was observed between either SARS-CoV-2-reactive IFN-γ CD8+ T cells or S-specific immunoglobulin G-antibody titers and blood cell count or levels of inflammatory biomarkers. In summary, in this descriptive, preliminary study we showed that SARS-CoV-2-reactive IFN-γ CD8+ T cells can be detected in a non-negligible percentage of patients with moderate to severe forms of COVID-19. Further studies are warranted to determine whether quantitation of these T-cell subsets may provide prognostic information on the clinical course of COVID-19.

Keywords: CD8+ T cells; COVID-19; SARS-CoV-2; T-cell immunity.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Viral / blood
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • COVID-19 / diagnosis
  • COVID-19 / immunology*
  • Female
  • Hospitalization
  • Humans
  • Immunoglobulin G / blood
  • Interferon-gamma / blood*
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Preliminary Data
  • Spike Glycoprotein, Coronavirus / immunology

Substances

  • Antibodies, Viral
  • Immunoglobulin G
  • Spike Glycoprotein, Coronavirus
  • spike glycoprotein, SARS-CoV
  • Interferon-gamma