Early antiviral CD4+ and CD8+ T cells are associated with upper airway clearance of SARS-CoV-2

JCI Insight. 2024 Dec 20;9(24):e186078. doi: 10.1172/jci.insight.186078.

Abstract

T cells are involved in protective immunity against numerous viral infections. Data regarding functional roles of human T cells in SARS-CoV-2 (SARS2) viral clearance in primary COVID-19 are limited. To address this knowledge gap, we assessed samples for associations between SARS2 upper respiratory tract viral RNA levels and early virus-specific adaptive immune responses for 95 unvaccinated clinical trial participants with acute primary COVID-19 aged 18-86 years old, approximately half of whom were considered at high risk for progression to severe COVID-19. Functionality and magnitude of acute SARS2-specific CD4+ and CD8+ T cell responses were evaluated, in addition to antibody responses. Most individuals with acute COVID-19 developed SARS2-specific T cell responses within 6 days of COVID-19 symptom onset. Early CD4+ T cell and CD8+ T cell responses were polyfunctional, and both strongly associated with reduced upper respiratory tract SARS2 viral RNA, independent of neutralizing antibody titers. Overall, these findings provide evidence for protective roles for circulating SARS2-specific CD4+ and CD8+ T cells during acute COVID-19.

Keywords: Adaptive immunity; Cellular immune response; Immunology; Infectious disease; T cells.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • CD4-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / immunology
  • COVID-19* / immunology
  • COVID-19* / virology
  • Female
  • Humans
  • Male
  • Middle Aged
  • RNA, Viral
  • SARS-CoV-2* / immunology
  • Young Adult

Substances

  • Antibodies, Viral
  • RNA, Viral
  • Antibodies, Neutralizing

Grants and funding

This work was supported in part by the National Institute of Allergy and Infectious diseases (NIAID) of the National Institutes of Health (NIH), Department of Health and Human Services, under contract no. 75N93019C00065 (A.S, D.W.), under awards AI036214, AI131385, UM1AI068634, UM1AI068636, and UM1AI106701. Additional support was provided in part by the John and Mary Tu Foundation, NIH T32 AI007036 (S.I.R.) and an A.P. Giannini Foundation fellowship award (S.I.R.). Bamlanivimab was donated by Eli Lilly and Company. The content presented is the sole responsibility of the authors and may not represent the opinions of the NIH.