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Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2

Long COVID (LC), a type of post-acute sequelae of SARS-CoV-2 infection (PASC), occurs after at least 10% of SARS-CoV-2 infections, yet its etiology remains poorly understood. Here, we used multiple “omics” assays (CyTOF, RNAseq/scRNAseq, Olink) and serology to deeply characterize both global and SAR...

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Autores principales: Yin, Kailin, Peluso, Michael J., Luo, Xiaoyu, Thomas, Reuben, Shin, Min-Gyoung, Neidleman, Jason, Andrew, Alicer, Young, Kyrlia, Ma, Tongcui, Hoh, Rebecca, Anglin, Khamal, Huang, Beatrice, Argueta, Urania, Lopez, Monica, Valdivieso, Daisy, Asare, Kofi, Deveau, Tyler-Marie, Munter, Sadie E., Ibrahim, Rania, Ständker, Ludger, Lu, Scott, Goldberg, Sarah A., Lee, Sulggi A., Lynch, Kara L., Kelly, J. Daniel, Martin, Jeffrey N., Münch, Jan, Deeks, Steven G., Henrich, Timothy J., Roan, Nadia R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934605/
https://www.ncbi.nlm.nih.gov/pubmed/36798286
http://dx.doi.org/10.1101/2023.02.09.527892
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author Yin, Kailin
Peluso, Michael J.
Luo, Xiaoyu
Thomas, Reuben
Shin, Min-Gyoung
Neidleman, Jason
Andrew, Alicer
Young, Kyrlia
Ma, Tongcui
Hoh, Rebecca
Anglin, Khamal
Huang, Beatrice
Argueta, Urania
Lopez, Monica
Valdivieso, Daisy
Asare, Kofi
Deveau, Tyler-Marie
Munter, Sadie E.
Ibrahim, Rania
Ständker, Ludger
Lu, Scott
Goldberg, Sarah A.
Lee, Sulggi A.
Lynch, Kara L.
Kelly, J. Daniel
Martin, Jeffrey N.
Münch, Jan
Deeks, Steven G.
Henrich, Timothy J.
Roan, Nadia R.
author_facet Yin, Kailin
Peluso, Michael J.
Luo, Xiaoyu
Thomas, Reuben
Shin, Min-Gyoung
Neidleman, Jason
Andrew, Alicer
Young, Kyrlia
Ma, Tongcui
Hoh, Rebecca
Anglin, Khamal
Huang, Beatrice
Argueta, Urania
Lopez, Monica
Valdivieso, Daisy
Asare, Kofi
Deveau, Tyler-Marie
Munter, Sadie E.
Ibrahim, Rania
Ständker, Ludger
Lu, Scott
Goldberg, Sarah A.
Lee, Sulggi A.
Lynch, Kara L.
Kelly, J. Daniel
Martin, Jeffrey N.
Münch, Jan
Deeks, Steven G.
Henrich, Timothy J.
Roan, Nadia R.
author_sort Yin, Kailin
collection PubMed
description Long COVID (LC), a type of post-acute sequelae of SARS-CoV-2 infection (PASC), occurs after at least 10% of SARS-CoV-2 infections, yet its etiology remains poorly understood. Here, we used multiple “omics” assays (CyTOF, RNAseq/scRNAseq, Olink) and serology to deeply characterize both global and SARS-CoV-2-specific immunity from blood of individuals with clear LC and non-LC clinical trajectories, 8 months following infection and prior to receipt of any SARS-CoV-2 vaccine. Our analysis focused on deep phenotyping of T cells, which play important roles in immunity against SARS-CoV-2 yet may also contribute to COVID-19 pathogenesis. Our findings demonstrate that individuals with LC exhibit systemic inflammation and immune dysregulation. This is evidenced by global differences in T cell subset distribution in ways that imply ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. Individuals with LC harbored increased frequencies of CD4+ T cells poised to migrate to inflamed tissues, and exhausted SARS-CoV-2-specific CD8+ T cells. They also harbored significantly higher levels of SARS-CoV-2 antibodies, and in contrast to non-LC individuals, exhibited a mis-coordination between their SARS-CoV-2-specific T and B cell responses. RNAseq/scRNAseq and Olink analyses similarly revealed immune dysregulatory mechanisms, along with non-immune associated perturbations, in individuals with LC. Collectively, our data suggest that proper crosstalk between the humoral and cellular arms of adaptive immunity has broken down in LC, and that this, perhaps in the context of persistent virus, leads to the immune dysregulation, inflammation, and clinical symptoms associated with this debilitating condition.
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spelling pubmed-99346052023-02-17 Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2 Yin, Kailin Peluso, Michael J. Luo, Xiaoyu Thomas, Reuben Shin, Min-Gyoung Neidleman, Jason Andrew, Alicer Young, Kyrlia Ma, Tongcui Hoh, Rebecca Anglin, Khamal Huang, Beatrice Argueta, Urania Lopez, Monica Valdivieso, Daisy Asare, Kofi Deveau, Tyler-Marie Munter, Sadie E. Ibrahim, Rania Ständker, Ludger Lu, Scott Goldberg, Sarah A. Lee, Sulggi A. Lynch, Kara L. Kelly, J. Daniel Martin, Jeffrey N. Münch, Jan Deeks, Steven G. Henrich, Timothy J. Roan, Nadia R. bioRxiv Article Long COVID (LC), a type of post-acute sequelae of SARS-CoV-2 infection (PASC), occurs after at least 10% of SARS-CoV-2 infections, yet its etiology remains poorly understood. Here, we used multiple “omics” assays (CyTOF, RNAseq/scRNAseq, Olink) and serology to deeply characterize both global and SARS-CoV-2-specific immunity from blood of individuals with clear LC and non-LC clinical trajectories, 8 months following infection and prior to receipt of any SARS-CoV-2 vaccine. Our analysis focused on deep phenotyping of T cells, which play important roles in immunity against SARS-CoV-2 yet may also contribute to COVID-19 pathogenesis. Our findings demonstrate that individuals with LC exhibit systemic inflammation and immune dysregulation. This is evidenced by global differences in T cell subset distribution in ways that imply ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. Individuals with LC harbored increased frequencies of CD4+ T cells poised to migrate to inflamed tissues, and exhausted SARS-CoV-2-specific CD8+ T cells. They also harbored significantly higher levels of SARS-CoV-2 antibodies, and in contrast to non-LC individuals, exhibited a mis-coordination between their SARS-CoV-2-specific T and B cell responses. RNAseq/scRNAseq and Olink analyses similarly revealed immune dysregulatory mechanisms, along with non-immune associated perturbations, in individuals with LC. Collectively, our data suggest that proper crosstalk between the humoral and cellular arms of adaptive immunity has broken down in LC, and that this, perhaps in the context of persistent virus, leads to the immune dysregulation, inflammation, and clinical symptoms associated with this debilitating condition. Cold Spring Harbor Laboratory 2023-08-04 /pmc/articles/PMC9934605/ /pubmed/36798286 http://dx.doi.org/10.1101/2023.02.09.527892 Text en https://creativecommons.org/licenses/by-nd/4.0/This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Yin, Kailin
Peluso, Michael J.
Luo, Xiaoyu
Thomas, Reuben
Shin, Min-Gyoung
Neidleman, Jason
Andrew, Alicer
Young, Kyrlia
Ma, Tongcui
Hoh, Rebecca
Anglin, Khamal
Huang, Beatrice
Argueta, Urania
Lopez, Monica
Valdivieso, Daisy
Asare, Kofi
Deveau, Tyler-Marie
Munter, Sadie E.
Ibrahim, Rania
Ständker, Ludger
Lu, Scott
Goldberg, Sarah A.
Lee, Sulggi A.
Lynch, Kara L.
Kelly, J. Daniel
Martin, Jeffrey N.
Münch, Jan
Deeks, Steven G.
Henrich, Timothy J.
Roan, Nadia R.
Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2
title Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2
title_full Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2
title_fullStr Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2
title_full_unstemmed Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2
title_short Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2
title_sort long covid manifests with t cell dysregulation, inflammation, and an uncoordinated adaptive immune response to sars-cov-2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934605/
https://www.ncbi.nlm.nih.gov/pubmed/36798286
http://dx.doi.org/10.1101/2023.02.09.527892
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