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Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19

2020; Cell Press; Volume: 53; Issue: 6 Linguagem: Inglês

10.1016/j.immuni.2020.11.017

1097-4180

Joana P. Bernardes, Neha Mishra, Florian Tran, Thomas Bahmer, Lena Best, Johanna I. Blase, Dora Bordoni, Jeanette Franzenburg, Ulf Geisen, Jonathan Josephs‐Spaulding, Philipp Köhler, Axel Künstner, Elisa Rosati, Anna C. Aschenbrenner, Petra Bächer, Nathan Baran, Teide Jens Boysen, Burkhard Brandt, Niklas Bruse, Jonathan Dörr, Andreas Dräger, Gunnar Elke, David Ellinghaus, Julia Fischer, Michael Förster, André Franke, Sören Franzenburg, Norbert Frey, Anette Friedrichs, Janina Fuß, Andreas Glück, Jacob Hamm, Finn Hinrichsen, Marc P. Hoeppner, Simon Imm, Ralf Junker, Sina Kaiser, Ying H. Kan, Rainer Knoll, Christoph Lange, Georg Laue, Clemens Lier, Matthias Lindner, Γεώργιος Μαρίνος, Robert Markewitz, Jacob Nattermann, Rainer Noth, Peter Pickkers, Klaus F. Rabe, Alina Renz, Christoph Röcken, Jan Rupp, Annika Schaffarzyk, Alexander Scheffold, Jonas Schulte-Schrepping, Domagoj Schunk, Dirk Skowasch, Thomas Ulas, Klaus‐Peter Wandinger, Michael Wittig, Johannes Zimmermann, Hauke Busch, Bimba F. Hoyer, Christoph Kaleta, Jan Heyckendorf, Matthijs Kox, Jan Rybniker, Stefan Schreiber, Joachim L. Schultze, Philip Rosenstiel, Nicholas E. Banovich, Tushar Desai, Oliver Eickelberg, Muzlifa Haniffa, Péter Horváth, Jonathan A. Kropski, Robert Lafyatis, Joakim Lundeberg, Kerstin B. Meyer, Martijn C. Nawijn, Marko Nikolić, José Ordovas Montañes, Dana Pe’er, Purushothama Rao Tata, Emma L. Rawlins, Aviv Regev, Paul A. Reyfman, Christos Samakovlis, Joachim L. Schultze, Alex K. Shalek, Douglas P. Shepherd, Jason R. Spence, Sarah A. Teichmann, Fabian J. Theis, Alexander M. Tsankov, Maarten van den Berge, Michael von Papen, Jeffrey A. Whitsett, Laure‐Emmanuelle Zaragosi, Angel Angelov, Robert Bals, Alexander Bartholomäus, Anke Becker, Daniela Bezdan, Ezio Bonifacio, Peer Bork, Thomas Clavel, Maria Colme-Tatche, Andreas Diefenbach, Alexander Dilthey, Nicole Fischer, Konrad U. Förstner, Julia-Stefanie Frick, Julien Gagneur, Alexander Goesmann, Torsten Hain, Michael Hummel, Stefan Janssen, Jörn Kalinowski, René Kallies, Birte Kehr, Andreas Keller, Sarah Kim-Hellmuth, Christoph Klein, Oliver Kohlbacher, Jan O. Korbel, Ingo Kurth, Markus Landthaler, Yang Li, Kerstin U. Ludwig, Oliwia Makarewicz, Manja Marz, Alice C. McHardy, Christian Mertes, Markus M. Nöthen, Peter Nürnberg, Uwe Ohler, Stephan Ossowski, Jörg Overmann, Silke Peter, Klaus Pfeffer, Anna R. Poetsch, Alfred Pühler, Nikolaus Rajewsky, Markus Ralser, Olaf Rieß, Stephan Ripke, Ulisses Nunes da Rocha, Philip Rosenstiel, Antoine‐Emmanuel Saliba, Leif Erik Sander, Birgit Sawitzki, Philipp H. Schiffer, Eva C. Schulte, Joachim L. Schultze, Alexander Sczyrba, Oliver Stegle, Jens Stoye, Fabian J. Theis, Jörg Janne Vehreschild, Jörg Vogel, Max von Kleist, Andreas Walker, Jörn Walter, Dagmar Wieczorek, John Ziebuhr,

SARS-CoV-2 and COVID-19 Research

Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We analyzed 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 interferon-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signaling. 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 adaptive immune cells and provides an entry point toward developing biomarkers and targeted treatments of patients with COVID-19.