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Longitudinal multi-omics analyses identify responses of megakaryocytes, erythroid cells, and plasmablasts as hallmarks of severe COVID-19

Item Type:Article
Title:Longitudinal multi-omics analyses identify responses of megakaryocytes, erythroid cells, and plasmablasts as hallmarks of severe COVID-19
Creators Name:Bernardes, J.P. and Mishra, N. and Tran, F. and Bahmer, T. and Best, L. and Blase, J.I. and Bordoni, D. and Franzenburg, J. and Geisen, U. and Josephs-Spaulding, J. and Köhler, P. and Künstner, A. and Rosati, E. and Aschenbrenner, A.C. and Bacher, P. and Baran, N. and Boysen, T. and Brandt, B. and Bruse, N. and Dörr, J. and Dräger, A. and Elke, G. and Ellinghaus, D. and Fischer, J. and Forster, M. and Franke, A. and Franzenburg, S. and Frey, N. and Friedrichs, A. and Fuß, J. and Glück, A. and Hamm, J. and Hinrichsen, F. and Hoeppner, M.P. and Imm, S. and Junker, R. and Kaiser, S. and Kan, Y.H. and Knoll, R. and Lange, C. and Laue, G. and Lier, C. and Lindner, M. and Marinos, G. and Markewitz, R. and Nattermann, J. and Noth, R. and Pickkers, P. and Rabe, K.F. and Renz, A. and Röcken, C. and Rupp, J. and Schaffarzyk, A. and Scheffold, A. and Schulte-Schrepping, J. and Schunk, D. and Skowasch, D. and Ulas, T. and Wandinger, K.P. and Wittig, M. and Zimmermann, J. and Busch, H. and Hoyer, B.F. and Kaleta, C. and Heyckendorf, J. and Kox, M. and Rybniker, J. and Schreiber, S. and Schultze, J.L. and Rosenstiel, P.
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.
Keywords:COVID-19, Virus, Blood, Immune Response, Disease Trajectory, Acute Respiratory Distress, Methylation, RNA-seq, scRNA-seq, Infectious Disease
Source:Immunity
ISSN:1074-7613
Publisher:Cell Press
Volume:53
Number:6
Page Range:1296-1314
Date:15 December 2020
Additional Information:Markus Landthaler, Uwe Ohler and Nikolaus Rajewsky are members of the Deutsche COVID-19 Omics Initiative (DeCOI).
Official Publication:https://doi.org/10.1016/j.immuni.2020.11.017
PubMed:View item in PubMed

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