Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19.
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.
Bernardes, JP; Mishra, N; Tran, F; Bahmer, T; Best, L; Blase, JI; Bordoni, D; Franzenburg, J; Geisen, U; Josephs-Spaulding, J; Köhler, P; Künstner, A; Rosati, E; Aschenbrenner, AC; 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, 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; 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, BF; Kaleta, C; Heyckendorf, J; Kox, M; Rybniker, J; Schreiber, S; Schultze, JL; Rosenstiel, P; HCA Lung Biological Network, ; Deutsche COVID-19 Omics Initiative (DeCOI),
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