| Autor: |
Jonathan Doerr, Dora Bordoni, Norbert Frey, Soeren Franzenburg, Burkhard Brandt, Ralf Juenker, Deutsche Covid Omics Initiative, Marc P. Hoeppner, Jacob Nattermann, Janina Fuss, Sina Kaiser, Rainer Noth, Alina Renz, Jan Rupp, Andreas Draeger, Niklas Bruse, Georgios Marinos, Robert Markewitz, Thomas Bahmer, Julia Fischer, Bimba F. Hoyer, Klaus F. Rabe, Philipp Koehler, Jan Rybniker, Domagoj Schunck, Klaus-Peter Wandinger, Axel Kuenstner, Thomas Ulas, Georg Laue, Jonathan Josephs-Spaulding, Michael Wittig, Andreas Glueck, Dirk Skowasch, Clemes Lier, Petra Bacher, Jan Heyckendorf, Christoph Kaleta, Stefan Schreiber, Matthias Lindner, Jonas Schulte-Schrepping, Joana P. Bernardes, Peter Pickkers, Ying H. Kan, Gunnar Elke, Philip Rosenstiel, Elisa Rosati, Alexander Scheffold, Teide Boysen, Christoph Roecken, Michael Forster, Matthijs Kox, Ulf Geisen, Jacob Hamm, Simon Imm, Johannes Zimmermann, Joachim L. Schultze, Andre Franke, Lena Best, David Ellinghaus, Jeanette Franzenburg, Annika Schaffarzyk, Rainer Knoll, Florian Tran, Hauke Busch, Finn Hinrichsen, Johanna I. Blase, Anna C. Aschenbrenner, Anette Friedrichs, Neha Mishra, Nathan Baran, Christoph Lange |
| Rok vydání: |
2020 |
| Předmět: |
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| Popis: |
The pandemic spread of the potentially life-threatening disease COVID-19 requires a thorough understanding of the longitudinal dynamics of host responses. Temporal resolution of cellular features associated with a severe disease trajectory will be a pre-requisite for finding disease outcome predictors. Here, we performed a longitudinal multi-omics study using a two-centre German cohort of 13 patients (from Cologne and Kiel, cohort 1). 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. The results from single-cell and bulk transcriptome analyses were validated in two independent cohorts of COVID-19 patients from Bonn (18 patients, cohort 2) and Nijmegen (40 patients, cohort 3), respectively. We observed an increase of proliferating, activated plasmablasts in severe COVID-19, and show a distinct expression pattern related to a hyperactive cellular metabolism of these cells. We further identified a notable expansion of type I IFN-activated circulating megakaryocytes and their progenitors, indicative of emergency megakaryopoiesis, which was confirmed in cohort 2. These changes were accompanied by increased erythropoiesis in the critical phase of the disease with features of hypoxic signalling. Finally, projecting megakaryocyte- and erythroid cell-derived co-expression modules to longitudinal blood transcriptome samples from cohort 3 confirmed an association of early temporal changes of these features with fatal COVID-19 disease outcome. In sum, our longitudinal multi-omics study demonstrates distinct cellular and gene expression dynamics upon SARS-CoV-2 infection, which point to metabolic shifts of circulating immune cells, and reveals changes in megakaryocytes and increased erythropoiesis as important outcome indicators in severe COVID-19 patients. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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