SARS-CoV-2-specific CD8+ T cells from people with [LC] establish and maintain effector phenotype and key TCR signatures over 2 years, 2024, Rowntree+

Discussion in 'Long Covid research' started by SNT Gatchaman, Sep 16, 2024.

  1. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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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
    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]
     
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  2. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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  3. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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  4. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    So why isn't that made clear in the abstract and why doesn't the abstract point out that the results were mostly the same for both groups? And why doesn't the title say so too?

    I haven't read the paper in detail because I doubt studies of T cell repertoire will tell us much but from what I can see the results tell us nothing much about Long Covid, just about the response to the virus in everybody.
     
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  5. Hutan

    Hutan Moderator Staff Member

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    This study made it on to the news on the radio and I've come here to find out more. I had the same reaction to the news item - there was nothing said about what was different with people with Long Covid and yet it was hailed as some important advance that would lead to a treatment. I hoped that the paper would actually have something interesting to say - that there was some difference.

    From the abstract, they didn't find any difference between what was happening in people who recovered and people with Long covid. I guess it's information, but I wouldn't have thought it was worth an item on the radio news.
     
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