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

HCA Lung Biological Network; the Deutsche COVID-19 Omics Initiative (DeCOI)

doi:10.1016/j.immuni.2020.11.017

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

HCA Lung Biological Network, the Deutsche COVID-19 Omics Initiative (DeCOI)

Abstract

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.

Originalsprache	Englisch
Zeitschrift	Immunity
Jahrgang	53
Ausgabenummer	6
Seiten (von - bis)	1296-1314.e9
ISSN	1074-7613
DOIs	https://doi.org/10.1016/j.immuni.2020.11.017
Publikationsstatus	Veröffentlicht - 15.12.2020

Fördermittel

We thank K. Greve, M. Rohm, M. Hansen, S. Kock, D. Oelsner, S. Baumgarten, M. Reffelmann, M. Schlapkohl, N. Braun, T. Wesse, M. Basso, Y. Dolschanskaya, X. Yi, C. Lancken, and M. Vollstedt for perfect technical assistance. This work was supported by the German Research Foundation (DFG) CCGA Nr. 07495230 , a COVID-response grant of the state SH , ExC 2167 Precision Medicine in Chronic Inflammation ( RTF-VI ), the research group miTARGET and the CRC1182 C2 project to P.R.; the IMI2 Project 3TR to P.R. and S.S.; INST 37/1049-1 , INST 216/981-1 , INST 257/605-1 , INST 269/768-1 , INST 217/988-1 , INST 217/577-1 , and EXC2151/1 ( 390873048 ) to J.L.S.; SFB TR57 and SPP1937 to J.N.; Helmholtz-Gemeinschaft Deutscher Forschungszentren, Germany ( sparse2big ) to J.L.S.; EU projects SYSCID ( 733100 ) to P.R. and J.L.S.; the DZIF, Germany ( TTU 04.816 and 04.817 ) to J.N.; and the Hector Foundation ) ( M89 ) to J.N. A.D. acknowledges support by the DFG ( EXC 2124-390838134 Controlling Microbes to Fight Infections) and the German Center for Infection Research (DZIF grant N° 8020708703). C.K. acknowledges support by the DFG through EXC 2167 , RTF-VIII , and the CRC 1182 . This publication is part of the Human Cell Atlas ( www.humancellatlas.org/publications ). We are indebted to the patients, their families, and the hospital staff for support, without whom this study would not have been possible.

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gesundheit und Wohlergehen
SDG 9 – Industrie, Innovation und Infrastruktur

Coronavirus-Bezug

Forschung zu SARS-CoV-2 / COVID-19

Dokumente

10.1016/j.immuni.2020.11.017

Weitere Links

Link to publication in Scopus

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@article{eb536c75473d470a86ba00af6d2119d0,

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

abstract = "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.",

author = "\{HCA Lung Biological Network\} and \{the Deutsche COVID-19 Omics Initiative (DeCOI)\} and Bernardes, \{Joana P.\} and Neha Mishra and Florian Tran and Thomas Bahmer and Lena Best and Blase, \{Johanna I.\} and Dora Bordoni and Jeanette Franzenburg and Ulf Geisen and Jonathan Josephs-Spaulding and Philipp K{\"o}hler and Axel K{\"u}nstner and Elisa Rosati and Aschenbrenner, \{Anna C.\} and Petra Bacher and Nathan Baran and Teide Boysen and Burkhard Brandt and Niklas Bruse and Jonathan D{\"o}rr and Andreas Dr{\"a}ger and Gunnar Elke and David Ellinghaus and Julia Fischer and Michael Forster and Andre Franke and S{\"o}ren Franzenburg and Norbert Frey and Anette Friedrichs and Janina Fu{\ss} and Andreas Gl{\"u}ck and Jacob Hamm and Finn Hinrichsen and Hoeppner, \{Marc P.\} and Simon Imm and Ralf Junker and Sina Kaiser and Kan, \{Ying H.\} and Rainer Knoll and Christoph Lange and Georg Laue and Clemens Lier and Matthias Lindner and Georgios Marinos and Robert Markewitz and Jacob Nattermann and Jan Rupp and Wandinger, \{Klaus Peter\} and Hauke Busch and Stefan Janssen",

note = "Funding Information: We thank K. Greve, M. Rohm, M. Hansen, S. Kock, D. Oelsner, S. Baumgarten, M. Reffelmann, M. Schlapkohl, N. Braun, T. Wesse, M. Basso, Y. Dolschanskaya, X. Yi, C. Lancken, and M. Vollstedt for perfect technical assistance. This work was supported by the German Research Foundation (DFG) CCGA Nr. 07495230 , a COVID-response grant of the state SH , ExC 2167 Precision Medicine in Chronic Inflammation ( RTF-VI ), the research group miTARGET and the CRC1182 C2 project to P.R.; the IMI2 Project 3TR to P.R. and S.S.; INST 37/1049-1 , INST 216/981-1 , INST 257/605-1 , INST 269/768-1 , INST 217/988-1 , INST 217/577-1 , and EXC2151/1 ( 390873048 ) to J.L.S.; SFB TR57 and SPP1937 to J.N.; Helmholtz-Gemeinschaft Deutscher Forschungszentren, Germany ( sparse2big ) to J.L.S.; EU projects SYSCID ( 733100 ) to P.R. and J.L.S.; the DZIF, Germany ( TTU 04.816 and 04.817 ) to J.N.; and the Hector Foundation ) ( M89 ) to J.N. A.D. acknowledges support by the DFG ( EXC 2124-390838134 Controlling Microbes to Fight Infections) and the German Center for Infection Research (DZIF grant N° 8020708703). C.K. acknowledges support by the DFG through EXC 2167 , RTF-VIII , and the CRC 1182 . This publication is part of the Human Cell Atlas ( www.humancellatlas.org/publications ). We are indebted to the patients, their families, and the hospital staff for support, without whom this study would not have been possible. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

month = dec,

day = "15",

doi = "10.1016/j.immuni.2020.11.017",

language = "English",

volume = "53",

pages = "1296--1314.e9",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "6",

}

Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19. / HCA Lung Biological Network; the Deutsche COVID-19 Omics Initiative (DeCOI).
in: Immunity, Jahrgang 53, Nr. 6, 15.12.2020, S. 1296-1314.e9.

Publikation: Beiträge in Fachzeitschriften › Zeitschriftenaufsätze › Forschung › Begutachtung

TY - JOUR

T1 - Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19

AU - HCA Lung Biological Network

AU - the Deutsche COVID-19 Omics Initiative (DeCOI)

AU - Bernardes, Joana P.

AU - Mishra, Neha

AU - Tran, Florian

AU - Bahmer, Thomas

AU - Best, Lena

AU - Blase, Johanna I.

AU - Bordoni, Dora

AU - Franzenburg, Jeanette

AU - Geisen, Ulf

AU - Josephs-Spaulding, Jonathan

AU - Köhler, Philipp

AU - Künstner, Axel

AU - Rosati, Elisa

AU - Aschenbrenner, Anna C.

AU - Bacher, Petra

AU - Baran, Nathan

AU - Boysen, Teide

AU - Brandt, Burkhard

AU - Bruse, Niklas

AU - Dörr, Jonathan

AU - Dräger, Andreas

AU - Elke, Gunnar

AU - Ellinghaus, David

AU - Fischer, Julia

AU - Forster, Michael

AU - Franke, Andre

AU - Franzenburg, Sören

AU - Frey, Norbert

AU - Friedrichs, Anette

AU - Fuß, Janina

AU - Glück, Andreas

AU - Hamm, Jacob

AU - Hinrichsen, Finn

AU - Hoeppner, Marc P.

AU - Imm, Simon

AU - Junker, Ralf

AU - Kaiser, Sina

AU - Kan, Ying H.

AU - Knoll, Rainer

AU - Lange, Christoph

AU - Laue, Georg

AU - Lier, Clemens

AU - Lindner, Matthias

AU - Marinos, Georgios

AU - Markewitz, Robert

AU - Nattermann, Jacob

AU - Rupp, Jan

AU - Wandinger, Klaus Peter

AU - Busch, Hauke

AU - Janssen, Stefan

N1 - Funding Information: We thank K. Greve, M. Rohm, M. Hansen, S. Kock, D. Oelsner, S. Baumgarten, M. Reffelmann, M. Schlapkohl, N. Braun, T. Wesse, M. Basso, Y. Dolschanskaya, X. Yi, C. Lancken, and M. Vollstedt for perfect technical assistance. This work was supported by the German Research Foundation (DFG) CCGA Nr. 07495230 , a COVID-response grant of the state SH , ExC 2167 Precision Medicine in Chronic Inflammation ( RTF-VI ), the research group miTARGET and the CRC1182 C2 project to P.R.; the IMI2 Project 3TR to P.R. and S.S.; INST 37/1049-1 , INST 216/981-1 , INST 257/605-1 , INST 269/768-1 , INST 217/988-1 , INST 217/577-1 , and EXC2151/1 ( 390873048 ) to J.L.S.; SFB TR57 and SPP1937 to J.N.; Helmholtz-Gemeinschaft Deutscher Forschungszentren, Germany ( sparse2big ) to J.L.S.; EU projects SYSCID ( 733100 ) to P.R. and J.L.S.; the DZIF, Germany ( TTU 04.816 and 04.817 ) to J.N.; and the Hector Foundation ) ( M89 ) to J.N. A.D. acknowledges support by the DFG ( EXC 2124-390838134 Controlling Microbes to Fight Infections) and the German Center for Infection Research (DZIF grant N° 8020708703). C.K. acknowledges support by the DFG through EXC 2167 , RTF-VIII , and the CRC 1182 . This publication is part of the Human Cell Atlas ( www.humancellatlas.org/publications ). We are indebted to the patients, their families, and the hospital staff for support, without whom this study would not have been possible. Publisher Copyright: © 2020 Elsevier Inc. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/12/15

Y1 - 2020/12/15

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85097363116

U2 - 10.1016/j.immuni.2020.11.017

DO - 10.1016/j.immuni.2020.11.017

M3 - Journal articles

C2 - 33296687

AN - SCOPUS:85097363116

SN - 1074-7613

VL - 53

SP - 1296-1314.e9

JO - Immunity

JF - Immunity

IS - 6

ER -

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

Abstract

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UN SDGs

Coronavirus-Bezug

Dokumente

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