@article{Mishra_N-2020_210020,
title = {Longitudinal multi-omics analyses identify responses of megakaryocytes, erythroid cells, and plasmablasts as hallmarks of severe COVID-19},
author = {Mishra, N. and Tran, F. and Bahmer, T. and Best, L. and Bordoni, D. and Franzenburg, J. and Geisen, U. and Josephs-Spaulding, J. and Köhler, P. and Künstner, A. and Rosati, E. 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 Imm, S. and Junker, R. and Kaiser, S. 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 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. and Wittig, M. and Zimmermann, J. and Busch, H. and Kaleta, C. and Heyckendorf, J. and Kox, M. and Rybniker, J. and Schreiber, S. and Rosenstiel, P. and Network, H. and (DeCOI), D. and Bernardes, J. and Blase, J. and Aschenbrenner, A. and Hoeppner, M. and Kan, Y. and Rabe, K. and Hoyer, B. and Schultze, J.},
month = {nov},
year = {2020},
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 (&gt;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.},
pages = {1296-1314},
volume = {53},
issue = {6},
journal = {Immunity},
publisher = {Elsevier},
url = {http://dx.doi.org/10.1016/j.immuni.2020.11.017},
}
