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

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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., Mishra, N., Tran, F., Bahmer, T., Best, L., Blase, J.I., Bordoni, D., Franzenburg, J., Geisen, U., Josephs-Spaulding, J., Köhler, P., Künstner, A., Rosati, E., Aschenbrenner, A.C., Bacher, P., Baran, N., Boysen, T., Brandt, B., Bruse, N., Dörr, J., Dräger, A., Elke, G., Ellinghaus, D., Fischer, J., Forster, M., Franke, A., Franzenburg, S., Frey, N., Friedrichs, A., Fuß, J., Glück, A., Hamm, J., Hinrichsen, F., Hoeppner, M.P., Imm, S., Junker, R., Kaiser, S., Kan, Y.H., Knoll, R., Lange, C., Laue, G., Lier, C., Lindner, M., Marinos, G., Markewitz, R., Nattermann, J., Noth, R., Pickkers, P., Rabe, K.F., Renz, A., Röcken, C., Rupp, J., Schaffarzyk, A., Scheffold, A., Schulte-Schrepping, J., Schunk, D., Skowasch, D., Ulas, T., Wandinger, K.P., Wittig, M., Zimmermann, J., Busch, H., Hoyer, B.F., Kaleta, C., Heyckendorf, J., Kox, M., Rybniker, J., Schreiber, S., 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). Copyright © 2020 Elsevier Inc.
Official Publication:	https://doi.org/10.1016/j.immuni.2020.11.017
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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