Immunity · 2020

Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19.

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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, Schunk 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 L, Rosenstiel Philip, HCA Lung Biological Network, Deutsche COVID-19 Omics Initiative (DeCOI)

Аннотация

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.

Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19.

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