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

被引：245

作者：

Bernardes, Joana P. ^{[1
,2
]}

Mishra, Neha ^{[1
,2
]}

Tran, Florian ^{[1
,2
,3
]}

Bahmer, Thomas ^{[3
]}

Best, Lena ^{[2
,4
]}

Blase, Johanna, I ^{[1
,2
]}

Bordoni, Dora ^{[1
,2
]}

Franzenburg, Jeanette ^{[1
,2
,5
,6
]}

Geisen, Ulf ^{[7
]}

Josephs-Spaulding, Jonathan ^{[2
,4
]}

Koehler, Philipp ^{[8
,9
,10
,11
,13
]}

Kuenstner, Axel ^{[12
]}

Rosati, Elisa ^{[1
,2
]}

Aschenbrenner, Anna C. ^{[15
,17
,18
,32
,33
,34
]}

Bacher, Petra ^{[1
,2
,16
]}

Baran, Nathan ^{[1
,2
]}

Boysen, Teide ^{[1
,2
]}

Brandt, Burkhard ^{[5
,6
]}

Bruse, Niklas ^{[17
,18
]}

Doerr, Jonathan ^{[7
]}

Draeger, Andreas ^{[19
,20
]}

Elke, Gunnar ^{[21
]}

Ellinghaus, David ^{[1
,2
]}

Fischer, Julia ^{[8
,9
,10
,11
,12
]}

Forster, Michael ^{[1
,2
]}

Franke, Andre ^{[1
,2
]}

Franzenburg, Soeren ^{[1
,2
]}

Frey, Norbert ^{[22
]}

Friedrichs, Anette ^{[3
]}

Fuss, Janina ^{[1
,2
]}

Glueck, Andreas ^{[3
]}

Hamm, Jacob ^{[1
,2
]}

Hinrichsen, Finn ^{[1
,2
]}

Hoeppner, Marc P. ^{[1
,2
]}

Imm, Simon ^{[1
,2
]}

Junker, Ralf ^{[5
,6
]}

Kaiser, Sina ^{[7
]}

Kan, Ying H. ^{[1
,2
]}

Knoll, Rainer ^{[32
,33
,34
]}

Lange, Christoph ^{[23
,24
]}

Laue, Georg ^{[1
,2
]}

Lier, Clemens ^{[5
,6
]}

Lindner, Matthias ^{[21
]}

Marinos, Georgios ^{[2
,4
]}

Markewitz, Robert ^{[5
,6
]}

Nattermann, Jacob ^{[25
,26
]}

Noth, Rainer ^{[3
]}

Pickkers, Peter ^{[17
,18
]}

Rabe, Klaus F. ^{[3
,27
]}

Renz, Alina ^{[19
,20
]}

机构：

[1] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany

[2] Univ Med Ctr Schleswig Holstein, D-24105 Kiel, Germany

[3] Univ Med Ctr Schleswig Holstein, Dept Internal Med 1, D-24105 Kiel, Germany

[4] Univ Kiel, Inst Expt Med, D-24105 Kiel, Germany

[5] Univ Med Ctr Schleswig Holstein, Inst Clin Chem, D-24105 Kiel, Germany

[6] Univ Med Ctr Schleswig Holstein, Inst Clin Chem, D-23562 Lubeck, Germany

[7] Univ Med Ctr Schleswig Holstein, Dept Internal Med 1, Sect Rheumatol, D-24105 Kiel, Germany

[8] Univ Cologne, Dept Internal Med 1, D-50931 Cologne, Germany

[9] Univ Hosp Cologne, D-50931 Cologne, Germany

[10] German Ctr Infect Res, Partner Site Bonn Cologne, D-50931 Cologne, Germany

[11] Univ Cologne, Ctr Mol Med Cologne, D-50931 Cologne, Germany

[12] Univ Cologne, Ctr Mol Med Cologne CMMC, D-50931 Cologne, Germany

[13] Cologne Excellence Cluster Cellular Stress Respon, D-50937 Cologne, Germany

[14] Univ Lubeck, Lubeck Inst Expt Dermatol, D-23562 Lubeck, Germany

[15] Univ Bonn, Life & Med Sci LIMES Inst, Genom & Immunoregulat, D-53115 Bonn, Germany

[16] Univ Med Ctr Schleswig Holstein, Inst Immunol, D-24105 Kiel, Germany

[17] Radboud Univ Nijmegen, Dept Intens Care Med, Med Ctr, NL-6500 HB Nijmegen, Netherlands

[18] Radboud Univ Nijmegen, Radboud Ctr Infect Dis RCI, Med Ctr, NL-6500 HB Nijmegen, Netherlands

[19] Univ Tubingen, Inst Bioinformat & Med Informat IBMI, Dept Comp Sci, D-72076 Tubingen, Germany

[20] German Ctr Infect Res DZIF, Partner Site Tubingen, D-72076 Tubingen, Germany

[21] Univ Med Ctr Schleswig Holstein, Dept Anaesthesiol & Intens Care Med, D-24105 Kiel, Germany

[22] Univ Med Ctr Schleswig Holstein, Dept Internal Med 3, D-24105 Kiel, Germany

[23] Res Ctr Borstel, Div Clin Infect Dis, D-23845 Borstel, Germany

[24] TTU TB, German Ctr Infect Res DZIF, D-23845 Borstel, Germany

[25] Univ Bonn, Dept Internal Med 1, D-53217 Bonn, Germany

[26] Univ Bonn, German Ctr Infect Res DZIF, D-53217 Bonn, Germany

[27] German Ctr Lung Res, Airway Res Ctr North, LungenClin Grosshansdorf, D-22927 Grosshansdorf, Germany

[28] Univ Med Ctr Schleswig Holstein, Dept Pathol, D-24105 Kiel, Germany

[29] Univ Lubeck, Dept Infect Dis & Microbiol, D-23562 Lubeck, Germany

[30] Univ Med Ctr Schleswig Holstein, Dept Emergency Med, D-24105 Kiel, Germany

[31] Univ Hosp Bonn, Dept Internal Med 2, Sect Pneumol, D-53127 Bonn, Germany

[32] German Ctr Neurodegenerat Dis DZNE, Syst Med, D-53127 Bonn, Germany

[33] DZNE, German Ctr Neurodegenerat Dis DZNE, PRECISE Platform Genom & Epigen, D-53127 Bonn, Germany

[34] Univ Bonn, D-53127 Bonn, Germany

来源：

IMMUNITY | 2020年 / 53卷 / 06期

关键词：

CORONAVIRUS DISEASE 2019; HEMATOPOIETIC STEM; INNATE IMMUNITY; HYPOXIA; DATABASE; DIFFERENTIATION; RECONSTRUCTION; INHIBITION; METABOLISM; EXPRESSION;

D O I：

10.1016/j.immuni.2020.11.017

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：1296 / +

页数：28

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