COVID-19 immune signatures reveal stable antiviral T cell function despite declining humoral responses

Immunity. 2021 Feb 9;54(2):340-354.e6. doi: 10.1016/j.immuni.2021.01.008.

Abstract

Cellular and humoral immunity to SARS-CoV-2 is critical to control primary infection and correlates with severity of disease. The role of SARS-CoV-2-specific T cell immunity, its relationship to antibodies, and pre-existing immunity against endemic coronaviruses (huCoV), which has been hypothesized to be protective, were investigated in 82 healthy donors (HDs), 204 recovered (RCs), and 92 active COVID-19 patients (ACs). ACs had high amounts of anti-SARS-CoV-2 nucleocapsid and spike IgG but lymphopenia and overall reduced antiviral T cell responses due to the inflammatory milieu, expression of inhibitory molecules (PD-1, Tim-3) as well as effector caspase-3, -7, and -8 activity in T cells. SARS-CoV-2-specific T cell immunity conferred by polyfunctional, mainly interferon-γ-secreting CD4+ T cells remained stable throughout convalescence, whereas humoral responses declined. Immune responses toward huCoV in RCs with mild disease and strong cellular SARS-CoV-2 T cell reactivity imply a protective role of pre-existing immunity against huCoV.

Keywords: COVID-19; SARS-CoV-2; antibody; antiviral T cell immunity; caspases; cell death; chemokine receptors; convalescence; endemic human coronavirus; humoral immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • COVID-19 / immunology*
  • Female
  • Humans
  • Immunity, Cellular / immunology*
  • Immunity, Humoral / immunology
  • Male
  • Middle Aged
  • SARS-CoV-2 / immunology
  • Young Adult

Substances

  • Antibodies, Viral