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COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis

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COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis. / Chua, Robert Lorenz; Lukassen, Soeren; Trump, Saskia; Hennig, Bianca P; Wendisch, Daniel; Pott, Fabian; Debnath, Olivia; Thürmann, Loreen; Kurth, Florian; Völker, Maria Theresa; Kazmierski, Julia; Timmermann, Bernd; Twardziok, Sven; Schneider, Stefan; Machleidt, Felix; Müller-Redetzky, Holger; Maier, Melanie; Krannich, Alexander; Schmidt, Sein; Balzer, Felix; Liebig, Johannes; Loske, Jennifer; Suttorp, Norbert; Eils, Jürgen; Ishaque, Naveed; Liebert, Uwe Gerd; von Kalle, Christof; Hocke, Andreas; Witzenrath, Martin; Goffinet, Christine; Drosten, Christian; Laudi, Sven; Lehmann, Irina; Conrad, Christian; Sander, Leif-Erik; Eils, Roland.

In: NAT BIOTECHNOL, Vol. 38, No. 8, 08.2020, p. 970-979.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Chua, RL, Lukassen, S, Trump, S, Hennig, BP, Wendisch, D, Pott, F, Debnath, O, Thürmann, L, Kurth, F, Völker, MT, Kazmierski, J, Timmermann, B, Twardziok, S, Schneider, S, Machleidt, F, Müller-Redetzky, H, Maier, M, Krannich, A, Schmidt, S, Balzer, F, Liebig, J, Loske, J, Suttorp, N, Eils, J, Ishaque, N, Liebert, UG, von Kalle, C, Hocke, A, Witzenrath, M, Goffinet, C, Drosten, C, Laudi, S, Lehmann, I, Conrad, C, Sander, L-E & Eils, R 2020, 'COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis', NAT BIOTECHNOL, vol. 38, no. 8, pp. 970-979. https://doi.org/10.1038/s41587-020-0602-4

APA

Chua, R. L., Lukassen, S., Trump, S., Hennig, B. P., Wendisch, D., Pott, F., Debnath, O., Thürmann, L., Kurth, F., Völker, M. T., Kazmierski, J., Timmermann, B., Twardziok, S., Schneider, S., Machleidt, F., Müller-Redetzky, H., Maier, M., Krannich, A., Schmidt, S., ... Eils, R. (2020). COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis. NAT BIOTECHNOL, 38(8), 970-979. https://doi.org/10.1038/s41587-020-0602-4

Vancouver

Chua RL, Lukassen S, Trump S, Hennig BP, Wendisch D, Pott F et al. COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis. NAT BIOTECHNOL. 2020 Aug;38(8):970-979. https://doi.org/10.1038/s41587-020-0602-4

Bibtex

@article{c24f9ce5a9d94b06a20716b7bcd56d12,
title = "COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis",
abstract = "To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand-receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF. The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19.",
keywords = "Adult, Aged, Angiotensin-Converting Enzyme 2, Bronchoalveolar Lavage Fluid/virology, COVID-19, Cell Communication, Cell Differentiation, Coronavirus Infections/pathology, Epithelial Cells/pathology, Female, Humans, Immune System/pathology, Inflammation/immunology, Longitudinal Studies, Male, Middle Aged, Nasopharynx/virology, Pandemics, Peptidyl-Dipeptidase A/genetics, Pneumonia, Viral/pathology, Respiratory System/immunology, Severity of Illness Index, Single-Cell Analysis, Transcriptome",
author = "Chua, {Robert Lorenz} and Soeren Lukassen and Saskia Trump and Hennig, {Bianca P} and Daniel Wendisch and Fabian Pott and Olivia Debnath and Loreen Th{\"u}rmann and Florian Kurth and V{\"o}lker, {Maria Theresa} and Julia Kazmierski and Bernd Timmermann and Sven Twardziok and Stefan Schneider and Felix Machleidt and Holger M{\"u}ller-Redetzky and Melanie Maier and Alexander Krannich and Sein Schmidt and Felix Balzer and Johannes Liebig and Jennifer Loske and Norbert Suttorp and J{\"u}rgen Eils and Naveed Ishaque and Liebert, {Uwe Gerd} and {von Kalle}, Christof and Andreas Hocke and Martin Witzenrath and Christine Goffinet and Christian Drosten and Sven Laudi and Irina Lehmann and Christian Conrad and Leif-Erik Sander and Roland Eils",
year = "2020",
month = aug,
doi = "10.1038/s41587-020-0602-4",
language = "English",
volume = "38",
pages = "970--979",
journal = "NAT BIOTECHNOL",
issn = "1087-0156",
publisher = "NATURE PUBLISHING GROUP",
number = "8",

}

RIS

TY - JOUR

T1 - COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis

AU - Chua, Robert Lorenz

AU - Lukassen, Soeren

AU - Trump, Saskia

AU - Hennig, Bianca P

AU - Wendisch, Daniel

AU - Pott, Fabian

AU - Debnath, Olivia

AU - Thürmann, Loreen

AU - Kurth, Florian

AU - Völker, Maria Theresa

AU - Kazmierski, Julia

AU - Timmermann, Bernd

AU - Twardziok, Sven

AU - Schneider, Stefan

AU - Machleidt, Felix

AU - Müller-Redetzky, Holger

AU - Maier, Melanie

AU - Krannich, Alexander

AU - Schmidt, Sein

AU - Balzer, Felix

AU - Liebig, Johannes

AU - Loske, Jennifer

AU - Suttorp, Norbert

AU - Eils, Jürgen

AU - Ishaque, Naveed

AU - Liebert, Uwe Gerd

AU - von Kalle, Christof

AU - Hocke, Andreas

AU - Witzenrath, Martin

AU - Goffinet, Christine

AU - Drosten, Christian

AU - Laudi, Sven

AU - Lehmann, Irina

AU - Conrad, Christian

AU - Sander, Leif-Erik

AU - Eils, Roland

PY - 2020/8

Y1 - 2020/8

N2 - To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand-receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF. The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19.

AB - To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand-receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF. The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19.

KW - Adult

KW - Aged

KW - Angiotensin-Converting Enzyme 2

KW - Bronchoalveolar Lavage Fluid/virology

KW - COVID-19

KW - Cell Communication

KW - Cell Differentiation

KW - Coronavirus Infections/pathology

KW - Epithelial Cells/pathology

KW - Female

KW - Humans

KW - Immune System/pathology

KW - Inflammation/immunology

KW - Longitudinal Studies

KW - Male

KW - Middle Aged

KW - Nasopharynx/virology

KW - Pandemics

KW - Peptidyl-Dipeptidase A/genetics

KW - Pneumonia, Viral/pathology

KW - Respiratory System/immunology

KW - Severity of Illness Index

KW - Single-Cell Analysis

KW - Transcriptome

U2 - 10.1038/s41587-020-0602-4

DO - 10.1038/s41587-020-0602-4

M3 - SCORING: Journal article

C2 - 32591762

VL - 38

SP - 970

EP - 979

JO - NAT BIOTECHNOL

JF - NAT BIOTECHNOL

SN - 1087-0156

IS - 8

ER -