Bernardes, Joana P., Mishra, Neha, Tran, Florian, Bahmer, Thomas, Best, Lena ORCID: 0000-0003-2772-153X, Blase, Johanna, I, Bordoni, Dora, Franzenburg, Jeanette, Geisen, Ulf ORCID: 0000-0002-6583-460X, Josephs-Spaulding, Jonathan ORCID: 0000-0001-9828-0685, Koehler, Philipp ORCID: 0000-0002-7386-7495, Kuenstner, Axel, Rosati, Elisa, Aschenbrenner, Anna C., Bacher, Petra, Baran, Nathan, Boysen, Teide, Brandt, Burkhard, Bruse, Niklas, Doerr, Jonathan, Draeger, Andreas, Elke, Gunnar, Ellinghaus, David, Fischer, Julia, Forster, Michael ORCID: 0000-0001-9927-5124, Franke, Andre, Franzenburg, Soeren, Frey, Norbert ORCID: 0000-0001-7611-378X, Friedrichs, Anette, Fuss, Janina, Glueck, Andreas, Hamm, Jacob, Hinrichsen, Finn, Hoeppner, Marc P., Imm, Simon, Junker, Ralf, Kaiser, Sina, Kan, Ying H., Knoll, Rainer, Lange, Christoph, Laue, Georg, Lier, Clemens, Lindner, Matthias, Marinos, Georgios, Markewitz, Robert, Nattermann, Jacob, Noth, Rainer, Pickkers, Peter, Rabe, Klaus F., Renz, Alina, Roecken, Christoph, Rupp, Jan, Schaffarzyk, Annika, Scheffold, Alexander ORCID: 0000-0002-0626-343X, Schulte-Schrepping, Jonas, Schunk, Domagoj, Skowasch, Dirk, Ulas, Thomas, Wandinger, Klaus-Peter, Wittig, Michael, Zimmermann, Johannes, Busch, Hauke, Hoyer, Bimba F., Kaleta, Christoph, Heyckendorf, Jan, Kox, Matthijs, Rybniker, Jan, Schreiber, Stefan, Schultze, Joachim L. and Rosenstiel, Philip (2020). Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19. Immunity, 53 (6). S. 1296 - 1324. CAMBRIDGE: CELL PRESS. ISSN 1097-4180

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Bernardes, Joana P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mishra, NehaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tran, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bahmer, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Best, LenaUNSPECIFIEDorcid.org/0000-0003-2772-153XUNSPECIFIED
Blase, Johanna, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bordoni, DoraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franzenburg, JeanetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geisen, UlfUNSPECIFIEDorcid.org/0000-0002-6583-460XUNSPECIFIED
Josephs-Spaulding, JonathanUNSPECIFIEDorcid.org/0000-0001-9828-0685UNSPECIFIED
Koehler, PhilippUNSPECIFIEDorcid.org/0000-0002-7386-7495UNSPECIFIED
Kuenstner, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosati, ElisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aschenbrenner, Anna C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bacher, PetraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baran, NathanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boysen, TeideUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brandt, BurkhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruse, NiklasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doerr, JonathanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Draeger, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Elke, GunnarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ellinghaus, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Forster, MichaelUNSPECIFIEDorcid.org/0000-0001-9927-5124UNSPECIFIED
Franke, AndreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franzenburg, SoerenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frey, NorbertUNSPECIFIEDorcid.org/0000-0001-7611-378XUNSPECIFIED
Friedrichs, AnetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fuss, JaninaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Glueck, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamm, JacobUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hinrichsen, FinnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoeppner, Marc P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Imm, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Junker, RalfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaiser, SinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kan, Ying H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knoll, RainerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lange, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laue, GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lier, ClemensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lindner, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marinos, GeorgiosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Markewitz, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nattermann, JacobUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noth, RainerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pickkers, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rabe, Klaus F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Renz, AlinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roecken, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rupp, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaffarzyk, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheffold, AlexanderUNSPECIFIEDorcid.org/0000-0002-0626-343XUNSPECIFIED
Schulte-Schrepping, JonasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schunk, DomagojUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Skowasch, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ulas, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wandinger, Klaus-PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wittig, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zimmermann, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Busch, HaukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoyer, Bimba F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaleta, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heyckendorf, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kox, MatthijsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rybniker, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schreiber, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schultze, Joachim L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenstiel, PhilipUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-307993
DOI: 10.1016/j.immuni.2020.11.017
Journal or Publication Title: Immunity
Volume: 53
Number: 6
Page Range: S. 1296 - 1324
Date: 2020
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4180
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HEMATOPOIETIC STEM; INNATE IMMUNITY; HYPOXIA; DATABASE; DIFFERENTIATION; RECONSTRUCTION; INHIBITION; METABOLISM; EXPRESSION; PLATELETSMultiple languages
ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/30799

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