Science and Research

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, J. P.
  • Mishra, N.
  • Tran, F.
  • Bahmer, T.
  • Best, L.
  • Blase, J. I.
  • Bordoni, D.
  • Franzenburg, J.
  • Geisen, U.
  • Josephs-Spaulding, J.
  • Köhler, P.
  • Künstner, A.
  • Rosati, E.
  • Aschenbrenner, A. C.
  • 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, M. P.
  • Imm, S.
  • Junker, R.
  • Kaiser, S.
  • Kan, Y. H.
  • Knoll, R.
  • Lange, C.
  • Laue, G.
  • Lier, C.
  • Lindner, M.
  • Marinos, G.
  • Markewitz, R.
  • Nattermann, J.
  • Noth, R.
  • Pickkers, P.
  • Rabe, K. F.
  • 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, B. F.
  • Kaleta, C.
  • Heyckendorf, J.
  • Kox, M.
  • Rybniker, J.
  • Schreiber, S.
  • Schultze, J. L.
  • Rosenstiel, P.

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Blood Circulation
  • COVID-19/immunology/*metabolism
  • Cells, Cultured
  • Cohort Studies
  • Disease Progression
  • Erythroid Cells/*pathology
  • Female
  • Gene Expression Profiling
  • Humans
  • Male
  • Megakaryocytes/*physiology
  • Middle Aged
  • Plasma Cells/*physiology
  • Proteomics
  • SARS-CoV-2/*physiology
  • Sequence Analysis, RNA
  • Severity of Illness Index
  • Single-Cell Analysis
  • *covid-19
  • *RNA-seq
  • *acute respiratory distress
  • *blood
  • *disease trajectory
  • *immune response
  • *infectious disease
  • *methylation
  • *scRNA-seq
  • *virus
Publication details
DOI: 10.1016/j.immuni.2020.11.017
Journal: Immunity
Pages: 1296-1314.e9 
Number: 6
Work Type: Original
Location: Assoziierter Partner, ARCN
Disease Area: PALI
Partner / Member: Ghd, UKSH (Kiel)
Access-Number: 33296687

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