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Seroconversion stages COVID19 into distinct pathophysiological states
COVID19 is a heterogeneous medical condition involving diverse underlying pathophysiological processes including hyperinflammation, endothelial damage, thrombotic microangiopathy, and end-organ damage. Limited knowledge about the molecular mechanisms driving these processes and lack of staging bioma...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963480/ https://www.ncbi.nlm.nih.gov/pubmed/33724185 http://dx.doi.org/10.7554/eLife.65508 |
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author | Galbraith, Matthew D Kinning, Kohl T Sullivan, Kelly D Baxter, Ryan Araya, Paula Jordan, Kimberly R Russell, Seth Smith, Keith P Granrath, Ross E Shaw, Jessica R Dzieciatkowska, Monika Ghosh, Tusharkanti Monte, Andrew A D'Alessandro, Angelo Hansen, Kirk C Benett, Tellen D Hsieh, Elena WY Espinosa, Joaquín M |
author_facet | Galbraith, Matthew D Kinning, Kohl T Sullivan, Kelly D Baxter, Ryan Araya, Paula Jordan, Kimberly R Russell, Seth Smith, Keith P Granrath, Ross E Shaw, Jessica R Dzieciatkowska, Monika Ghosh, Tusharkanti Monte, Andrew A D'Alessandro, Angelo Hansen, Kirk C Benett, Tellen D Hsieh, Elena WY Espinosa, Joaquín M |
author_sort | Galbraith, Matthew D |
collection | PubMed |
description | COVID19 is a heterogeneous medical condition involving diverse underlying pathophysiological processes including hyperinflammation, endothelial damage, thrombotic microangiopathy, and end-organ damage. Limited knowledge about the molecular mechanisms driving these processes and lack of staging biomarkers hamper the ability to stratify patients for targeted therapeutics. We report here the results of a cross-sectional multi-omics analysis of hospitalized COVID19 patients revealing that seroconversion status associates with distinct underlying pathophysiological states. Low antibody titers associate with hyperactive T cells and NK cells, high levels of IFN alpha, gamma and lambda ligands, markers of systemic complement activation, and depletion of lymphocytes, neutrophils, and platelets. Upon seroconversion, all of these processes are attenuated, observing instead increases in B cell subsets, emergency hematopoiesis, increased D-dimer, and hypoalbuminemia. We propose that seroconversion status could potentially be used as a biosignature to stratify patients for therapeutic intervention and to inform analysis of clinical trial results in heterogenous patient populations. |
format | Online Article Text |
id | pubmed-7963480 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-79634802021-03-17 Seroconversion stages COVID19 into distinct pathophysiological states Galbraith, Matthew D Kinning, Kohl T Sullivan, Kelly D Baxter, Ryan Araya, Paula Jordan, Kimberly R Russell, Seth Smith, Keith P Granrath, Ross E Shaw, Jessica R Dzieciatkowska, Monika Ghosh, Tusharkanti Monte, Andrew A D'Alessandro, Angelo Hansen, Kirk C Benett, Tellen D Hsieh, Elena WY Espinosa, Joaquín M eLife Immunology and Inflammation COVID19 is a heterogeneous medical condition involving diverse underlying pathophysiological processes including hyperinflammation, endothelial damage, thrombotic microangiopathy, and end-organ damage. Limited knowledge about the molecular mechanisms driving these processes and lack of staging biomarkers hamper the ability to stratify patients for targeted therapeutics. We report here the results of a cross-sectional multi-omics analysis of hospitalized COVID19 patients revealing that seroconversion status associates with distinct underlying pathophysiological states. Low antibody titers associate with hyperactive T cells and NK cells, high levels of IFN alpha, gamma and lambda ligands, markers of systemic complement activation, and depletion of lymphocytes, neutrophils, and platelets. Upon seroconversion, all of these processes are attenuated, observing instead increases in B cell subsets, emergency hematopoiesis, increased D-dimer, and hypoalbuminemia. We propose that seroconversion status could potentially be used as a biosignature to stratify patients for therapeutic intervention and to inform analysis of clinical trial results in heterogenous patient populations. eLife Sciences Publications, Ltd 2021-03-16 /pmc/articles/PMC7963480/ /pubmed/33724185 http://dx.doi.org/10.7554/eLife.65508 Text en © 2021, Galbraith et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology and Inflammation Galbraith, Matthew D Kinning, Kohl T Sullivan, Kelly D Baxter, Ryan Araya, Paula Jordan, Kimberly R Russell, Seth Smith, Keith P Granrath, Ross E Shaw, Jessica R Dzieciatkowska, Monika Ghosh, Tusharkanti Monte, Andrew A D'Alessandro, Angelo Hansen, Kirk C Benett, Tellen D Hsieh, Elena WY Espinosa, Joaquín M Seroconversion stages COVID19 into distinct pathophysiological states |
title | Seroconversion stages COVID19 into distinct pathophysiological states |
title_full | Seroconversion stages COVID19 into distinct pathophysiological states |
title_fullStr | Seroconversion stages COVID19 into distinct pathophysiological states |
title_full_unstemmed | Seroconversion stages COVID19 into distinct pathophysiological states |
title_short | Seroconversion stages COVID19 into distinct pathophysiological states |
title_sort | seroconversion stages covid19 into distinct pathophysiological states |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963480/ https://www.ncbi.nlm.nih.gov/pubmed/33724185 http://dx.doi.org/10.7554/eLife.65508 |
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