SARS-CoV-2-specific CD8+ T cells from people with long COVID establish and maintain effector phenotype and key TCR signatures over 2 years
Details
Publication Year 2024-09-24,Volume 121,Issue #39,Page e2411428121
Journal Title
Proceedings of the National Academy of Sciences of the United States of America
Publication Type
Research article
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(+) and CD4(+) 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(+) and CD4(+) 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(+) 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.
Publisher
National Academy of Sciences
Keywords
Humans; *CD8-Positive T-Lymphocytes/immunology; *SARS-CoV-2/immunology; *COVID-19/immunology; *Receptors, Antigen, T-Cell/immunology/metabolism; 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; SARS-CoV-2 epitopes; T cell receptors; T cells; long COVID
Department(s)
Infectious Diseases
Open Access at Publisher's Site
https://doi.org/10.1073/pnas.2411428121
Terms of Use/Rights Notice
Refer to copyright notice on published article.


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