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10.1016/j.immuni.2020.11.017

http://scihub22266oqcxt.onion/10.1016/j.immuni.2020.11.017
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suck abstract from ncbi


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pmid33296687      Immunity 2020 ; 53 (6): 1296-1314.e9
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  • Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19 #MMPMID33296687
  • Bernardes JP; Mishra N; Tran F; Bahmer T; Best L; Blase JI; Bordoni D; Franzenburg J; Geisen U; Josephs-Spaulding J; Kohler P; Kunstner A; Rosati E; Aschenbrenner AC; Bacher P; Baran N; Boysen T; Brandt B; Bruse N; Dorr J; Drager A; Elke G; Ellinghaus D; Fischer J; Forster M; Franke A; Franzenburg S; Frey N; Friedrichs A; Fuss J; Gluck 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; Rocken C; Rupp J; Schaffarzyk A; Scheffold A; Schulte-Schrepping J; Schunk D; Skowasch D; Ulas T; Wandinger KP; Wittig M; Zimmermann J; Busch H; Hoyer BF; Kaleta C; Heyckendorf J; Kox M; Rybniker J; Schreiber S; Schultze JL; Rosenstiel P
  • Immunity 2020[Dec]; 53 (6): 1296-1314.e9 PMID33296687show ga
  • 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.
  • |Adult[MESH]
  • |Aged[MESH]
  • |Aged, 80 and over[MESH]
  • |Biomarkers[MESH]
  • |Blood Circulation[MESH]
  • |COVID-19/immunology/*metabolism[MESH]
  • |Cells, Cultured[MESH]
  • |Cohort Studies[MESH]
  • |Disease Progression[MESH]
  • |Erythroid Cells/*pathology[MESH]
  • |Female[MESH]
  • |Gene Expression Profiling[MESH]
  • |Humans[MESH]
  • |Male[MESH]
  • |Megakaryocytes/*physiology[MESH]
  • |Middle Aged[MESH]
  • |Plasma Cells/*physiology[MESH]
  • |Proteomics[MESH]
  • |SARS-CoV-2/*physiology[MESH]
  • |Sequence Analysis, RNA[MESH]
  • |Severity of Illness Index[MESH]


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