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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
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.
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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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