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

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<sup>+</sup> and CD4<sup>+</sup> 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<sup>+</sup> and CD4<sup>+</sup> 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<sup>+</sup> 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.

Authors

Institutions

Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2024-09-16
DOI
https://doi.org/10.1073/pnas.2411428121
Citations
15
Primary Topic
Long-Term Effects of COVID-19
Type
article
Field-Weighted Citation Impact
5.54

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

Prathanporn Kaewpreedee, Adam K. Wheatley, Katherine Kedzierska, Malik Peiris et al.
15 citations
Proceedings of the National Academy of Sciences
Long-Term Effects of COVID-19
5.54
article

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

Prathanporn Kaewpreedee, Adam K. Wheatley, Katherine Kedzierska, Malik Peiris, Samuel M. S. Cheng, Jennifer R. Habel, Jan Petersen, Priyanka Chaurasia, Dhilshan Jayasinghe, Thi H. O. Nguyen, Allen Cheng, Leo L. M. Poon, Jason A. Trubiano, Isabelle J. H. Foo, Hayley A. McQuilten, Jennifer A. Juno, Lydia Murdiyarso, Louise C. Rowntree, Stephen John Kent, Sophie A. Valkenburg, Janette Kwok, Jennifer Audsley, Sharon R. Lewin, Hyon‐Xhi Tan, Dene R. Littler, Peter C. Doherty, Wuji Zhang, Natasha E. Holmes, Jamie Rossjohn, Ruth R. Hagen, Stéphanie Gras, David S.C. Hui, Ka Pang Chan, Irani Thevarajan, Tom Kotsimbos, Kelly W. K. Lee, Elizabeth R. V. ten Berge, Lilith F. Allen, Hanujah Ganesh
article en
15 citations

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<sup>+</sup> and CD4<sup>+</sup> 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<sup>+</sup> and CD4<sup>+</sup> 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<sup>+</sup> 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.

Proceedings of the National Academy of SciencesVol. 121(39)
The Royal Melbourne Hospital (AU), The University of Melbourne (AU), Chinese University of Hong Kong (HK), La Trobe University (AU), Peter MacCallum Cancer Centre (AU), Queen Mary Hospital (CN), Hong Kong Science and Technology Parks Corporation (HK), Australian Regenerative Medicine Institute (AU), The Alfred Hospital (AU), Peter Doherty Institute (AU), Prince of Wales Hospital (CN), Monash Health (AU), HKU-Pasteur Research Pole (HK), Austin Health (AU), Monash University (AU), Cardiff University (GB), University of Hong Kong (HK)
Snow Medical, National Health and Medical Research Council, Health and Medical Research Fund
Openalex Percentile: Top 3%
Long-Term Effects of COVID-19
5.54
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.