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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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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. |
format | Online Article Text |
id | pubmed-9934605 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
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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