SARS-CoV-2-specific CD8+ T cells from people with long COVID establish and maintain effector phenotype and key TCR signatures over 2 years

Rowntree, LC; Audsley, J; Allen, LF; McQuilten, HA; Hagen, RR; Chaurasia, P; Petersen, J; Littler, DR; Tan, HX; Murdiyarso, L; Habel, JR; Foo, IJH; Zhang, W; Ten Berge, ERV; Ganesh, H; Kaewpreedee, P; Lee, KWK; Cheng, SMS; Kwok, JSY; Jayasinghe, D; Gras, S; Juno, JA; Wheatley, AK; Kent, SJ; Rossjohn, J; Cheng, AC; Kotsimbos, TC; Trubiano, JA; Holmes, NE; Pang Chan, KK; Hui, DSC; Peiris, M; Poon, LLM; Lewin, SR; Doherty, PC; Thevarajan, I; Valkenburg, SA; Kedzierska, K; Nguyen, THO

Author(s): Rowntree, LC; Audsley, J; Allen, LF; McQuilten, HA; Hagen, RR; Chaurasia, P; Petersen, J; Littler, DR; Tan, HX; Murdiyarso, L; Habel, JR; Foo, IJH; Zhang, W; Ten Berge, ERV; Ganesh, H; Kaewpreedee, P; Lee, KWK; Cheng, SMS; Kwok, JSY; Jayasinghe, D; Gras, S; Juno, JA; Wheatley, AK; Kent, SJ; Rossjohn, J; Cheng, AC; Kotsimbos, TC; Trubiano, JA; Holmes, NE; Pang Chan, KK; Hui, DSC; Peiris, M; Poon, LLM; Lewin, SR; Doherty, PC; Thevarajan, I; Valkenburg, SA; Kedzierska, K; Nguyen, THO;
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
Publisher's Version: https://doi.org/10.1073/pnas.2411428121
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.

Creation Date: 2024-10-01 07:30:55

Last Modified: 2024-10-01 07:37:32