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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.
  • Frishberg A; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Institute of Computational Biology, Helmholtz Center Munich, 85764 Neuherberg, Germany; Department of Immunology, Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
  • Kooistra E; Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Nuesch-Germano M; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Pecht T; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Milman N; Department of Immunology, Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
  • Reusch N; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Warnat-Herresthal S; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Bruse N; Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Händler K; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE and University of Bonn, Bonn, Germany.
  • Theis H; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE and University of Bonn, Bonn, Germany.
  • Kraut M; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE and University of Bonn, Bonn, Germany.
  • van Rijssen E; Laboratory for Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
  • van Cranenbroek B; Laboratory for Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
  • Koenen HJ; Laboratory for Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
  • Heesakkers H; Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
  • van den Boogaard M; Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Zegers M; Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Pickkers P; Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Becker M; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE and University of Bonn, Bonn, Germany.
  • Aschenbrenner AC; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud Uni
  • Ulas T; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE and University of Bonn, Bonn, Germany.
  • Theis FJ; Institute of Computational Biology, Helmholtz Center Munich, 85764 Neuherberg, Germany; Department of Mathematics, Technical University of Munich, 85748 Garching, Germany; Technical University of Munich, TUM School of Life Sciences Weihenstephan, 85354 Freising, Germany.
  • Shen-Orr SS; Department of Immunology, Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
  • Schultze JL; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), PRECISE Platform for Genomics an
  • Kox M; Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
Cell Rep Med ; 3(6): 100652, 2022 06 21.
Article in English | MEDLINE | ID: covidwho-1960088
ABSTRACT
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: NF-kappa B / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Cell Rep Med Year: 2022 Document Type: Article Affiliation country: J.xcrm.2022.100652

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Full text: Available Collection: International databases Database: MEDLINE Main subject: NF-kappa B / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Cell Rep Med Year: 2022 Document Type: Article Affiliation country: J.xcrm.2022.100652