| Autor: |
Jan Heyckendorf, Elisa Rosati, Jens Stoye, Andreas Dräger, Alex K. Shalek, Daniela Bezdan, Norbert Frey, Ulisses Nunes da Rocha, Thomas Bahmer, Simon Imm, Antoine-Emmanuel Saliba, Markus Landthaler, Ezio Bonifacio, Maria Colme-Tatche, Annika Schaffarzyk, Alexander Sczyrba, Dora Bordoni, David Ellinghaus, Christoph Lange, Stefan Janssen, Nicholas E. Banovich, Laure-Emmanuelle Zaragosi, Markus M. Nöthen, Anette Friedrichs, Alexander M. Tsankov, Teide Boysen, Andreas Glück, Philipp H. Schiffer, Lena Best, Oliver Eickelberg, Silke Peter, Nathan Baran, Maarten van den Berge, Oliver Kohlbacher, Anna R. Poetsch, Michael Hummel, Ulf Geisen, Dagmar Wieczorek, Alexander T. Dilthey, Burkhard Brandt, Kerstin B. Meyer, Christian Mertes, Jonas Schulte-Schrepping, Florian Tran, Birgit Sawitzki, Hauke Busch, Christoph Klein, Christos Samakovlis, Niklaus Rajewsky, Joachim Schultze, Sören Franzenburg, Jörn Walter, Sina Kaiser, Jörg Vogel, Niklas Bruse, Marc P. Hoeppner, Muzlifa Haniffa, Alina Renz, Purushothama Rao Tata, Stephan Ripke, Ralf Junker, Michael von Papen, Jonathan A. Kropski, Max von Kleist, Oliver Stegle, Neha Mishra, Jörg Overmann, Johanna I. Blase, Nicole Fischer, Jeffrey A. Whitsett, Sarah A. Teichmann, Birte Kehr, Domagoj Schunk, Julia Fischer, Andreas Diefenbach, Joakim Lundeberg, Matthijs Kox, Klaus-Peter Wandinger, Michael Forster, Ingo Kurth, Johannes Zimmermann, Yang Li, René Kallies, Petra Bacher, Torsten Hain, Joachim L. Schultze, Clemens Lier, Klaus Pfeffer, Michael Wittig, Jacob Nattermann, Paul A. Reyfman, Peter Nürnberg, Alfred Pühler, Andre Franke, Markus Ralser, Peter Pickkers, Andreas Keller, Matthias Lindner, Philipp Köhler, Dana Pe'er, Gunnar Elke, Jan Rybniker, Jonathan Josephs-Spaulding, Alexander Goesmann, Anke Becker, Aviv Regev, Ying H. Kan, Alexander Bartholomäus, Rainer Noth, Jonathan Dörr, Julia-Stefanie Frick, Stephan Ossowski, Bimba F. Hoyer, Peter Horvath, Jose Ordovas Montanes, Dirk Skowasch, Philip Rosenstiel, Georg Laue, Oliwia Makarewicz, Stefan Schreiber, Alexander Scheffold, Christoph Röcken, Leif E. Sander, Manja Marz, Joana P. Bernardes, Jörn Kalinowski, Uwe Ohler, Robert Markewitz, Jason R. Spence, Robert Lafyatis, Thomas Ulas, Peer Bork, Tushar J. Desai, Janne Vehreschild, Janina Fuß, Olaf Rieß, Robert Bals, Klaus F. Rabe, Jacob Hamm, Martijn C. Nawijn, John Ziebuhr, Angel Angelov, Fabian J. Theis, Rainer Knoll, Jan O. Korbel, Thomas Clavel, Konrad U. Förstner, Jan Rupp, Sarah Kim-Hellmuth, Christoph Kaleta, Alice C. McHardy, Anna C. Aschenbrenner, Emma L. Rawlins, Douglas P. Shepherd, Julien Gagneur, Marko Nikolic, Georgios Marinos, Jeanette Franzenburg, Eva-Christina Schulte, Axel Künstner, Andreas Walker, Finn Hinrichsen, Kerstin U. Ludwig |
| Přispěvatelé: |
Groningen Research Institute for Asthma and COPD (GRIAC), HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany., BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany. |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Immunity, 53, 1296-1314.e9
Immunity, 53(6), 1296-1314.e9. CELL PRESS
Immunity 53(6), 1296-1314.e9 (2020). doi:10.1016/j.immuni.2020.11.017
Immunity
Immunity, 53, 6, pp. 1296-1314.e9
1314.e9
United States |
| ISSN: |
1074-7613 |
| DOI: |
10.1016/j.immuni.2020.11.017 |
| Popis: |
Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is required for understanding skewed immune responses and finding outcome predictors. Here, we performed a longitudinal multi-omics study using a two-centre cohort of 14 patients. We analysed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (>358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points. Validation was performed in two independent cohorts of COVID-19 patients. Severe COVID-19 was characterized by an increase of proliferating, metabolically hyperactive plasmablasts. Coinciding with critical illness, we also identified an expansion of IFN-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signalling. Megakaryocyte- and erythroid cell-derived co-expression modules were predictive of fatal disease outcome. The study demonstrates broad cellular effects of SARS-CoV-2 infection beyond classical immune cells and may serve as an entry point to develop biomarkers and targeted treatments of patients with COVID-19.
Graphical Abstract
Highlights • SARS-CoV2 infection elicits dynamic changes of circulating cells in the blood • Severe COVID-19 is characterized by increased metabolically active plasmablasts • Elevation of IFN-activated megakaryocytes and erythroid cells in severe COVID-19 • Cell-type specific expression signatures are associated with a fatal COVID-19 outcome
Bernardes et al. explore COVID-19 disease trajectories by performing longitudinal multi-omics analyses in peripheral blood samples from hospitalized patients. The analyses identify increased numbers of plasmablasts, interferon-activated megakaryocytes and erythroid cells as hallmarks of severe disease, and define molecular signatures linked to a fatal COVID-19 disease outcome. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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