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SARS-CoV-2-specific CD8 + T cells from people with long COVID establish and maintain effector phenotype and key TCR signatures over 2 years.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Sep 24; Vol. 121 (39), pp. e2411428121. Date of Electronic Publication: 2024 Sep 16. - Publication Year :
- 2024
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Abstract
- Long COVID occurs in a small but important minority of patients following COVID-19, reducing quality of life and contributing to healthcare burden. Although research into underlying mechanisms is evolving, immunity is understudied. SARS-CoV-2-specific T cell responses are of key importance for viral clearance and COVID-19 recovery. However, in long COVID, the establishment and persistence of SARS-CoV-2-specific T cells are far from clear, especially beyond 12 mo postinfection and postvaccination. We defined ex vivo antigen-specific B cell and T cell responses and their T cell receptors (TCR) repertoires across 2 y postinfection in people with long COVID. Using 13 SARS-CoV-2 peptide-HLA tetramers, spanning 11 HLA allotypes, as well as spike and nucleocapsid probes, we tracked SARS-CoV-2-specific CD8 <superscript>+</superscript> and CD4 <superscript>+</superscript> T cells and B-cells in individuals from their first SARS-CoV-2 infection through primary vaccination over 24 mo. The frequencies of ORF1a- and nucleocapsid-specific T cells and B cells remained stable over 24 mo. Spike-specific CD8 <superscript>+</superscript> and CD4 <superscript>+</superscript> T cells and B cells were boosted by SARS-CoV-2 vaccination, indicating immunization, in fully recovered and people with long COVID, altered the immunodominance hierarchy of SARS-CoV-2 T cell epitopes. Meanwhile, influenza-specific CD8 <superscript>+</superscript> T cells were stable across 24 mo, suggesting no bystander-activation. Compared to total T cell populations, SARS-CoV-2-specific T cells were enriched for central memory phenotype, although the proportion of central memory T cells decreased following acute illness. Importantly, TCR repertoire composition was maintained throughout long COVID, including postvaccination, to 2 y postinfection. Overall, we defined ex vivo SARS-CoV-2-specific B cells and T cells to understand primary and recall responses, providing key insights into antigen-specific responses in people with long COVID.<br />Competing Interests: Competing interests statement:Hayley McQuilten consults for Ena Respiratory.
- Subjects :
- Humans
Epitopes, T-Lymphocyte immunology
Spike Glycoprotein, Coronavirus immunology
Middle Aged
Male
Female
Post-Acute COVID-19 Syndrome
Phenotype
B-Lymphocytes immunology
Immunologic Memory immunology
Coronavirus Nucleocapsid Proteins immunology
Aged
CD8-Positive T-Lymphocytes immunology
SARS-CoV-2 immunology
COVID-19 immunology
Receptors, Antigen, T-Cell immunology
Receptors, Antigen, T-Cell metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 121
- Issue :
- 39
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 39284068
- Full Text :
- https://doi.org/10.1073/pnas.2411428121