Author: Bernardes, Joana P.; Mishra, Neha; Tran, Florian; Bahmer, Thomas; Best, Lena; Blase, Johanna I.; Bordoni, Dora; Franzenburg, Jeanette; Geisen, Ulf; Josephs-Spaulding, Jonathan; Köhler, Philipp; Künstner, Axel; Rosati, Elisa; Aschenbrenner, Anna C.; Bacher, Petra; Baran, Nathan; Boysen, Teide; Brandt, Burkhard; Bruse, Niklas; Dörr, Jonathan; Dräger, Andreas; Elke, Gunnar; Ellinghaus, David; Fischer, Julia; Forster, Michael; Franke, Andre; Franzenburg, Sören; Frey, Norbert; Friedrichs, Anette; Fuß, Janina; Glück, Andreas; Hamm, Jacob; Hinrichsen, Finn; Hoeppner, Marc P.; Imm, Simon; Junker, Ralf; Kaiser, Sina; Kan, Ying H.; Knoll, Rainer; Lange, Christoph; Laue, Georg; Lier, Clemens; Lindner, Matthias; Marinos, Georgios; Markewitz, Robert; Nattermann, Jacob; Noth, Rainer; Pickkers, Peter; Rabe, Klaus F.; Renz, Alina; Röcken, Christoph; Rupp, Jan; Schaffarzyk, Annika; Scheffold, Alexander; Schulte-Schrepping, Jonas; Schunck, Domagoj; Skowasch, Dirk; Ulas, Thomas; Wandinger, Klaus-Peter; Wittig, Michael; Zimmermann, Johannes; Busch, Hauke; Hoyer, Bimba F.; Kaleta, Christoph; Heyckendorf, Jan; Kox, Matthijs; Rybniker, Jan; Schreiber, Stefan; Schultze, Joachim; Rosenstiel, Philip
Title: Longitudinal multi-omics analyses identify responses of megakaryocytes, erythroid cells and plasmablasts as hallmarks of severe COVID-19 trajectories Cord-id: qbg1g92r Document date: 2020_11_26
ID: qbg1g92r
Snippet: Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is required for understanding skewed immune responses and finding outcome predictors. Here, we performed a longitudinal multi-omics study using a two-centre cohort of 14 patients. We analysed 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 ind
Document: Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is required for understanding skewed immune responses and finding outcome predictors. Here, we performed a longitudinal multi-omics study using a two-centre cohort of 14 patients. We analysed 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 IFN-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signalling. 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 classical immune cells and may serve as an entry point to develop biomarkers and targeted treatments of patients with COVID-19.
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