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

Bernardes JP, Mishra N, Tran F, Bahmer T, Best L, Blase J, Bordoni D, Franzenburg J, Geisen U, Josephs-Spaulding J, Koehler P, Kuenstner A, Rosati E, Aschenbrenner AC, Bacher P, Baran N, Boysen T, Brandt B, Bruse N, Doerr J, Draeger A, Elke G, Ellinghaus D, Fischer J, Forster M, Franke A, Franzenburg S, Frey N, Friedrichs A, Fuss J, Glueck A, Hamm J, Hinrichsen F, Hoeppner MP, Imm S, Junker R, Kaiser S, Kan YH, Knoll R, Lange C, Laue G, Lier C, Lindner M, Marinos G, Markewitz R, Nattermann J, Noth R, Pickkers P, Rabe KF, Renz A, Roecken C, Rupp J, Schaffarzyk A, Scheffold A, Schulte-Schrepping J, Schunk D, Skowasch D, Ulas T, Wandinger KP, Wittig M, Zimmermann J, Busch H, Hoyer BF, Kaleta C, Heyckendorf J, Kox M, Rybniker J, Schreiber S, Schultze JL, Rosenstiel P (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Immunity Elsevier

Book Volume: 53

Pages Range: 1296-1314.e9

Journal Issue: 6

DOI: 10.1016/j.immuni.2020.11.017

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.

Involved external institutions

Universität zu Köln DE Germany (DE) Christian-Albrechts-Universität zu Kiel DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Universitätsklinikum Bonn DE Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Universität zu Lübeck DE Germany (DE) Radboud University Nijmegen NL Netherlands (NL) Eberhard Karls Universität Tübingen DE Germany (DE) Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) DE Germany (DE) Forschungszentrum Borstel - Leibniz-Zentrum für Medizin und Biowissenschaften / Research Center Borstel - Leibniz-Center for Medicine and Biosciences DE Germany (DE)

How to cite

APA:

Bernardes, J.P., Mishra, N., Tran, F., Bahmer, T., Best, L., Blase, J.,... Rosenstiel, P. (2020). Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19. Immunity, 53(6), 1296-1314.e9. https://doi.org/10.1016/j.immuni.2020.11.017

MLA:

Bernardes, Joana P., et al. "Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19." Immunity 53.6 (2020): 1296-1314.e9.

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