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Mature neutrophils and a NF-κB-to-IFN transition determine the unifying disease recovery dynamics in COVID-19

Disease recovery dynamics are often difficult to assess, as patients display heterogeneous recovery courses. To model recovery dynamics, exemplified by severe COVID-19, we apply a computational scheme on longitudinally sampled blood transcriptomes, generating recovery states, which we then link to c...

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Autores principales: Frishberg, Amit, Kooistra, Emma, Nuesch-Germano, Melanie, Pecht, Tal, Milman, Neta, Reusch, Nico, Warnat-Herresthal, Stefanie, Bruse, Niklas, Händler, Kristian, Theis, Heidi, Kraut, Michael, van Rijssen, Esther, van Cranenbroek, Bram, Koenen, Hans JPM., Heesakkers, Hidde, van den Boogaard, Mark, Zegers, Marieke, Pickkers, Peter, Becker, Matthias, Aschenbrenner, Anna C., Ulas, Thomas, Theis, Fabian J., Shen-Orr, Shai S., Schultze, Joachim L., Kox, Matthijs
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110324/
https://www.ncbi.nlm.nih.gov/pubmed/35675822
http://dx.doi.org/10.1016/j.xcrm.2022.100652
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author Frishberg, Amit
Kooistra, Emma
Nuesch-Germano, Melanie
Pecht, Tal
Milman, Neta
Reusch, Nico
Warnat-Herresthal, Stefanie
Bruse, Niklas
Händler, Kristian
Theis, Heidi
Kraut, Michael
van Rijssen, Esther
van Cranenbroek, Bram
Koenen, Hans JPM.
Heesakkers, Hidde
van den Boogaard, Mark
Zegers, Marieke
Pickkers, Peter
Becker, Matthias
Aschenbrenner, Anna C.
Ulas, Thomas
Theis, Fabian J.
Shen-Orr, Shai S.
Schultze, Joachim L.
Kox, Matthijs
author_facet Frishberg, Amit
Kooistra, Emma
Nuesch-Germano, Melanie
Pecht, Tal
Milman, Neta
Reusch, Nico
Warnat-Herresthal, Stefanie
Bruse, Niklas
Händler, Kristian
Theis, Heidi
Kraut, Michael
van Rijssen, Esther
van Cranenbroek, Bram
Koenen, Hans JPM.
Heesakkers, Hidde
van den Boogaard, Mark
Zegers, Marieke
Pickkers, Peter
Becker, Matthias
Aschenbrenner, Anna C.
Ulas, Thomas
Theis, Fabian J.
Shen-Orr, Shai S.
Schultze, Joachim L.
Kox, Matthijs
author_sort Frishberg, Amit
collection PubMed
description Disease recovery dynamics are often difficult to assess, as patients display heterogeneous recovery courses. To model recovery dynamics, exemplified by severe COVID-19, we apply a computational scheme on longitudinally sampled blood transcriptomes, generating recovery states, which we then link to cellular and molecular mechanisms, presenting a framework for studying the kinetics of recovery compared with non-recovery over time and long-term effects of the disease. Specifically, a decrease in mature neutrophils is the strongest cellular effect during recovery, with direct implications on disease outcome. Furthermore, we present strong indications for global regulatory changes in gene programs, decoupled from cell compositional changes, including an early rise in T cell activation and differentiation, resulting in immune rebalancing between interferon and NF-κB activity and restoration of cell homeostasis. Overall, we present a clinically relevant computational framework for modeling disease recovery, paving the way for future studies of the recovery dynamics in other diseases and tissues.
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spelling pubmed-91103242022-05-17 Mature neutrophils and a NF-κB-to-IFN transition determine the unifying disease recovery dynamics in COVID-19 Frishberg, Amit Kooistra, Emma Nuesch-Germano, Melanie Pecht, Tal Milman, Neta Reusch, Nico Warnat-Herresthal, Stefanie Bruse, Niklas Händler, Kristian Theis, Heidi Kraut, Michael van Rijssen, Esther van Cranenbroek, Bram Koenen, Hans JPM. Heesakkers, Hidde van den Boogaard, Mark Zegers, Marieke Pickkers, Peter Becker, Matthias Aschenbrenner, Anna C. Ulas, Thomas Theis, Fabian J. Shen-Orr, Shai S. Schultze, Joachim L. Kox, Matthijs Cell Rep Med Article Disease recovery dynamics are often difficult to assess, as patients display heterogeneous recovery courses. To model recovery dynamics, exemplified by severe COVID-19, we apply a computational scheme on longitudinally sampled blood transcriptomes, generating recovery states, which we then link to cellular and molecular mechanisms, presenting a framework for studying the kinetics of recovery compared with non-recovery over time and long-term effects of the disease. Specifically, a decrease in mature neutrophils is the strongest cellular effect during recovery, with direct implications on disease outcome. Furthermore, we present strong indications for global regulatory changes in gene programs, decoupled from cell compositional changes, including an early rise in T cell activation and differentiation, resulting in immune rebalancing between interferon and NF-κB activity and restoration of cell homeostasis. Overall, we present a clinically relevant computational framework for modeling disease recovery, paving the way for future studies of the recovery dynamics in other diseases and tissues. Elsevier 2022-05-17 /pmc/articles/PMC9110324/ /pubmed/35675822 http://dx.doi.org/10.1016/j.xcrm.2022.100652 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Frishberg, Amit
Kooistra, Emma
Nuesch-Germano, Melanie
Pecht, Tal
Milman, Neta
Reusch, Nico
Warnat-Herresthal, Stefanie
Bruse, Niklas
Händler, Kristian
Theis, Heidi
Kraut, Michael
van Rijssen, Esther
van Cranenbroek, Bram
Koenen, Hans JPM.
Heesakkers, Hidde
van den Boogaard, Mark
Zegers, Marieke
Pickkers, Peter
Becker, Matthias
Aschenbrenner, Anna C.
Ulas, Thomas
Theis, Fabian J.
Shen-Orr, Shai S.
Schultze, Joachim L.
Kox, Matthijs
Mature neutrophils and a NF-κB-to-IFN transition determine the unifying disease recovery dynamics in COVID-19
title Mature neutrophils and a NF-κB-to-IFN transition determine the unifying disease recovery dynamics in COVID-19
title_full Mature neutrophils and a NF-κB-to-IFN transition determine the unifying disease recovery dynamics in COVID-19
title_fullStr Mature neutrophils and a NF-κB-to-IFN transition determine the unifying disease recovery dynamics in COVID-19
title_full_unstemmed Mature neutrophils and a NF-κB-to-IFN transition determine the unifying disease recovery dynamics in COVID-19
title_short Mature neutrophils and a NF-κB-to-IFN transition determine the unifying disease recovery dynamics in COVID-19
title_sort mature neutrophils and a nf-κb-to-ifn transition determine the unifying disease recovery dynamics in covid-19
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110324/
https://www.ncbi.nlm.nih.gov/pubmed/35675822
http://dx.doi.org/10.1016/j.xcrm.2022.100652
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