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Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19
COVID-19 exhibits extensive patient-to-patient heterogeneity. To link immune response variation to disease severity and outcome over time, we longitudinally assessed circulating proteins as well as 188 surface protein markers, transcriptome, and T cell receptor sequence simultaneously in single peri...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Published by Elsevier Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874909/ https://www.ncbi.nlm.nih.gov/pubmed/33713619 http://dx.doi.org/10.1016/j.cell.2021.02.018 |
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author | Liu, Can Martins, Andrew J. Lau, William W. Rachmaninoff, Nicholas Chen, Jinguo Imberti, Luisa Mostaghimi, Darius Fink, Danielle L. Burbelo, Peter D. Dobbs, Kerry Delmonte, Ottavia M. Bansal, Neha Failla, Laura Sottini, Alessandra Quiros-Roldan, Eugenia Han, Kyu Lee Sellers, Brian A. Cheung, Foo Sparks, Rachel Chun, Tae-Wook Moir, Susan Lionakis, Michail S. Rossi, Camillo Su, Helen C. Kuhns, Douglas B. Cohen, Jeffrey I. Notarangelo, Luigi D. Tsang, John S. |
author_facet | Liu, Can Martins, Andrew J. Lau, William W. Rachmaninoff, Nicholas Chen, Jinguo Imberti, Luisa Mostaghimi, Darius Fink, Danielle L. Burbelo, Peter D. Dobbs, Kerry Delmonte, Ottavia M. Bansal, Neha Failla, Laura Sottini, Alessandra Quiros-Roldan, Eugenia Han, Kyu Lee Sellers, Brian A. Cheung, Foo Sparks, Rachel Chun, Tae-Wook Moir, Susan Lionakis, Michail S. Rossi, Camillo Su, Helen C. Kuhns, Douglas B. Cohen, Jeffrey I. Notarangelo, Luigi D. Tsang, John S. |
author_sort | Liu, Can |
collection | PubMed |
description | COVID-19 exhibits extensive patient-to-patient heterogeneity. To link immune response variation to disease severity and outcome over time, we longitudinally assessed circulating proteins as well as 188 surface protein markers, transcriptome, and T cell receptor sequence simultaneously in single peripheral immune cells from COVID-19 patients. Conditional-independence network analysis revealed primary correlates of disease severity, including gene expression signatures of apoptosis in plasmacytoid dendritic cells and attenuated inflammation but increased fatty acid metabolism in CD56(dim)CD16(hi) NK cells linked positively to circulating interleukin (IL)-15. CD8(+) T cell activation was apparent without signs of exhaustion. Although cellular inflammation was depressed in severe patients early after hospitalization, it became elevated by days 17–23 post symptom onset, suggestive of a late wave of inflammatory responses. Furthermore, circulating protein trajectories at this time were divergent between and predictive of recovery versus fatal outcomes. Our findings stress the importance of timing in the analysis, clinical monitoring, and therapeutic intervention of COVID-19. |
format | Online Article Text |
id | pubmed-7874909 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Published by Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78749092021-02-11 Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19 Liu, Can Martins, Andrew J. Lau, William W. Rachmaninoff, Nicholas Chen, Jinguo Imberti, Luisa Mostaghimi, Darius Fink, Danielle L. Burbelo, Peter D. Dobbs, Kerry Delmonte, Ottavia M. Bansal, Neha Failla, Laura Sottini, Alessandra Quiros-Roldan, Eugenia Han, Kyu Lee Sellers, Brian A. Cheung, Foo Sparks, Rachel Chun, Tae-Wook Moir, Susan Lionakis, Michail S. Rossi, Camillo Su, Helen C. Kuhns, Douglas B. Cohen, Jeffrey I. Notarangelo, Luigi D. Tsang, John S. Cell Article COVID-19 exhibits extensive patient-to-patient heterogeneity. To link immune response variation to disease severity and outcome over time, we longitudinally assessed circulating proteins as well as 188 surface protein markers, transcriptome, and T cell receptor sequence simultaneously in single peripheral immune cells from COVID-19 patients. Conditional-independence network analysis revealed primary correlates of disease severity, including gene expression signatures of apoptosis in plasmacytoid dendritic cells and attenuated inflammation but increased fatty acid metabolism in CD56(dim)CD16(hi) NK cells linked positively to circulating interleukin (IL)-15. CD8(+) T cell activation was apparent without signs of exhaustion. Although cellular inflammation was depressed in severe patients early after hospitalization, it became elevated by days 17–23 post symptom onset, suggestive of a late wave of inflammatory responses. Furthermore, circulating protein trajectories at this time were divergent between and predictive of recovery versus fatal outcomes. Our findings stress the importance of timing in the analysis, clinical monitoring, and therapeutic intervention of COVID-19. Published by Elsevier Inc. 2021-04-01 2021-02-10 /pmc/articles/PMC7874909/ /pubmed/33713619 http://dx.doi.org/10.1016/j.cell.2021.02.018 Text en © 2021 Published by Elsevier Inc. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Liu, Can Martins, Andrew J. Lau, William W. Rachmaninoff, Nicholas Chen, Jinguo Imberti, Luisa Mostaghimi, Darius Fink, Danielle L. Burbelo, Peter D. Dobbs, Kerry Delmonte, Ottavia M. Bansal, Neha Failla, Laura Sottini, Alessandra Quiros-Roldan, Eugenia Han, Kyu Lee Sellers, Brian A. Cheung, Foo Sparks, Rachel Chun, Tae-Wook Moir, Susan Lionakis, Michail S. Rossi, Camillo Su, Helen C. Kuhns, Douglas B. Cohen, Jeffrey I. Notarangelo, Luigi D. Tsang, John S. Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19 |
title | Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19 |
title_full | Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19 |
title_fullStr | Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19 |
title_full_unstemmed | Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19 |
title_short | Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19 |
title_sort | time-resolved systems immunology reveals a late juncture linked to fatal covid-19 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874909/ https://www.ncbi.nlm.nih.gov/pubmed/33713619 http://dx.doi.org/10.1016/j.cell.2021.02.018 |
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