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, Louise C.; Audsley, Jennifer; Allen, Lilith F.; McQuilten, Hayley A.; Hagen, Ruth R.; Chaurasia, Priyanka; Petersen, Jan; Littler, Dene R.; Tan, Hyon-Xhi; Murdiyarso, Lydia; Habel, Jennifer R.; Foo, Isabelle J. H.; Zhang, Wuji; ten Berge, Elizabeth R. V.; Ganesh, Hanujah; Kaewpreedee, Prathanporn; Lee, Kelly W. K.; Cheng, Samuel M. S.; Kwok, Janette S. Y.; Jayasinghe, Dhilshan; Gras, Stephanie; Juno, Jennifer A.; Wheatley, Adam K.; Kent, Stephen J.; Rossjohn, Jamie; Cheng, Allen C.; Kotsimbos, Tom C.; Trubiano, Jason A.; Holmes, Natasha E.; Pang Chan, Ken Ka; Hui, David S. C.; Peiris, Malik; Poon, Leo L. M.; Lewin, Sharon R.; Doherty, Peter C.; Thevarajan, Irani; Valkenburg, Sophie A.; Kedzierska, Katherine; Nguyen, Thi H. O.
SIGNIFICANCE
Long COVID occurs in 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. As the recall of T cell memory promotes more rapid recovery and ameliorates disease outcomes, establishment of robust memory T cells is important for protection against subsequent infections, even when the virus mutates.
We defined how SARS-CoV-2-specific T cell and B cell responses are established and maintained following infection and vaccination for 2 y in people with long COVID. We found robust and prototypical SARS-CoV-2-specific T cells with effector phenotype and key T cell receptor signatures in people with long COVID following SARS-CoV-2 infection and subsequent COVID-19 vaccination.
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.
Link | PDF (Proceedings of the National Academy of Sciences) [Open Access]
Rowntree, Louise C.; Audsley, Jennifer; Allen, Lilith F.; McQuilten, Hayley A.; Hagen, Ruth R.; Chaurasia, Priyanka; Petersen, Jan; Littler, Dene R.; Tan, Hyon-Xhi; Murdiyarso, Lydia; Habel, Jennifer R.; Foo, Isabelle J. H.; Zhang, Wuji; ten Berge, Elizabeth R. V.; Ganesh, Hanujah; Kaewpreedee, Prathanporn; Lee, Kelly W. K.; Cheng, Samuel M. S.; Kwok, Janette S. Y.; Jayasinghe, Dhilshan; Gras, Stephanie; Juno, Jennifer A.; Wheatley, Adam K.; Kent, Stephen J.; Rossjohn, Jamie; Cheng, Allen C.; Kotsimbos, Tom C.; Trubiano, Jason A.; Holmes, Natasha E.; Pang Chan, Ken Ka; Hui, David S. C.; Peiris, Malik; Poon, Leo L. M.; Lewin, Sharon R.; Doherty, Peter C.; Thevarajan, Irani; Valkenburg, Sophie A.; Kedzierska, Katherine; Nguyen, Thi H. O.
SIGNIFICANCE
Long COVID occurs in 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. As the recall of T cell memory promotes more rapid recovery and ameliorates disease outcomes, establishment of robust memory T cells is important for protection against subsequent infections, even when the virus mutates.
We defined how SARS-CoV-2-specific T cell and B cell responses are established and maintained following infection and vaccination for 2 y in people with long COVID. We found robust and prototypical SARS-CoV-2-specific T cells with effector phenotype and key T cell receptor signatures in people with long COVID following SARS-CoV-2 infection and subsequent COVID-19 vaccination.
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.
Link | PDF (Proceedings of the National Academy of Sciences) [Open Access]
