Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity.

dc.contributor.author

Bui, Linh T

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Winters, Nichelle I

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Chung, Mei-I

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Joseph, Chitra

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Gutierrez, Austin J

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Habermann, Arun C

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Adams, Taylor S

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Schupp, Jonas C

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Poli, Sergio

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Peter, Lance M

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Taylor, Chase J

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Blackburn, Jessica B

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Richmond, Bradley W

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Nicholson, Andrew G

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Rassl, Doris

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Wallace, William A

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Rosas, Ivan O

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Jenkins, R Gisli

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Kaminski, Naftali

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Kropski, Jonathan A

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Banovich, Nicholas E

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Human Cell Atlas Lung Biological Network

dc.date.accessioned

2024-02-01T17:58:20Z

dc.date.available

2024-02-01T17:58:20Z

dc.date.issued

2021-07

dc.description.abstract

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observe a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD AT2 cells express higher levels of genes linked directly to the efficiency of viral replication and the innate immune response. Additionally, we identify basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.

dc.identifier

10.1038/s41467-021-24467-0

dc.identifier.issn

2041-1723

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2041-1723

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https://hdl.handle.net/10161/30083

dc.language

eng

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Springer Science and Business Media LLC

dc.relation.ispartof

Nature communications

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10.1038/s41467-021-24467-0

dc.rights.uri

https://creativecommons.org/licenses/by-nc/4.0

dc.subject

Human Cell Atlas Lung Biological Network

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Lung

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Humans

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Lung Diseases

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Chronic Disease

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Inflammation

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Virus Replication

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Virus Internalization

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Immunity, Innate

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Idiopathic Pulmonary Fibrosis

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Transcriptome

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Alveolar Epithelial Cells

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COVID-19

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Angiotensin-Converting Enzyme 2

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SARS-CoV-2

dc.title

Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity.

dc.type

Journal article

pubs.begin-page

4314

pubs.issue

1

pubs.organisational-group

Duke

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School of Medicine

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Basic Science Departments

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Clinical Science Departments

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Institutes and Centers

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Cell Biology

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Medicine

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Medicine, Pulmonary, Allergy, and Critical Care Medicine

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Duke Cancer Institute

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Regeneration Next Initiative

pubs.publication-status

Published

pubs.volume

12

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