Differential T-Cell Reactivity to Endemic Coronaviruses and SARS-CoV-2 in Community and Health Care Workers

J Infect Dis. 2021 Jul 2;224(1):70-80. doi: 10.1093/infdis/jiab176.


Herein we measured CD4+ T-cell responses against common cold coronaviruses (CCC) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in high-risk health care workers (HCW) and community controls. We observed higher levels of CCC-reactive T cells in SARS-CoV-2-seronegative HCW compared to community donors, consistent with potential higher occupational exposure of HCW to CCC. We further show that SARS-CoV-2 T-cell reactivity of seronegative HCW was higher than community controls and correlation between CCC and SARS-CoV-2 responses is consistent with cross-reactivity and not associated with recent in vivo activation. Surprisingly, CCC T-cell reactivity was decreased in SARS-CoV-2-infected HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses, either directly or indirectly. This result was unexpected, but consistently detected in independent cohorts derived from Miami and San Diego. CD4+ T-cell responses against common cold coronaviruses (CCC) are elevated in SARS-CoV-2 seronegative high-risk health care workers (HCW) compared to COVID-19 convalescent HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses and/or cross-reactivity associated with a protective effect.

Keywords: COVID-19; SARS-CoV-2; T cells; coronaviruses; health care workers.

Publication types

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

MeSH terms

  • Adult
  • Antibodies, Viral
  • Biomarkers
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • COVID-19 / diagnosis
  • COVID-19 / epidemiology*
  • COVID-19 / immunology*
  • COVID-19 / virology
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Health Personnel*
  • Humans
  • Immunophenotyping
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Peptides / chemistry
  • Peptides / immunology
  • Public Health Surveillance
  • SARS-CoV-2 / immunology*
  • Seroepidemiologic Studies
  • Severity of Illness Index
  • Spike Glycoprotein, Coronavirus / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism


  • Antibodies, Viral
  • Biomarkers
  • Epitopes, T-Lymphocyte
  • Peptides
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2