Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS
Aartik Sarma,
Stephanie A. Christenson,
Ashley Byrne,
Eran Mick,
Angela Oliveira Pisco,
Catherine DeVoe,
Thomas Deiss,
Rajani Ghale,
Beth Shoshana Zha,
Alexandra Tsitsiklis,
Alejandra Jauregui,
Farzad Moazed,
Angela M. Detweiler,
Natasha Spottiswoode,
Pratik Sinha,
Norma Neff,
Michelle Tan,
Paula Hayakawa Serpa,
Andrew Willmore,
K. Mark Ansel,
Jennifer G. Wilson,
Aleksandra Leligdowicz,
Emily R. Siegel,
Marina Sirota,
Joseph L. DeRisi,
Michael A. Matthay,
Carolyn M. Hendrickson,
Kirsten N. Kangelaris,
Matthew F. Krummel,
Prescott G. Woodruff,
David J. Erle,
Carolyn S. Calfee and
Charles R. Langelier ()
Additional contact information
Aartik Sarma: University of California
Stephanie A. Christenson: University of California
Ashley Byrne: Chan Zuckerberg Biohub
Eran Mick: University of California
Angela Oliveira Pisco: Chan Zuckerberg Biohub
Catherine DeVoe: University of California
Thomas Deiss: Chan Zuckerberg Biohub
Rajani Ghale: University of California
Beth Shoshana Zha: University of California
Alexandra Tsitsiklis: University of California
Alejandra Jauregui: University of California
Farzad Moazed: University of California
Angela M. Detweiler: University of California
Natasha Spottiswoode: University of California
Pratik Sinha: Washington University
Norma Neff: Chan Zuckerberg Biohub
Michelle Tan: Chan Zuckerberg Biohub
Paula Hayakawa Serpa: University of California
Andrew Willmore: University of California
K. Mark Ansel: University of California
Jennifer G. Wilson: Stanford University
Aleksandra Leligdowicz: University of California
Emily R. Siegel: University of California
Marina Sirota: University of California
Joseph L. DeRisi: Chan Zuckerberg Biohub
Michael A. Matthay: University of California
Carolyn M. Hendrickson: University of California
Kirsten N. Kangelaris: University of California
Matthew F. Krummel: University of California
Prescott G. Woodruff: University of California
David J. Erle: University of California
Carolyn S. Calfee: University of California
Charles R. Langelier: Chan Zuckerberg Biohub
Nature Communications, 2021, vol. 12, issue 1, 1-10
Abstract:
Abstract The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results of comparative lower respiratory tract transcriptional profiling of tracheal aspirate from 52 critically ill patients with ARDS from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a “cytokine storm,” we observe reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS is characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity. In silico analysis of gene expression identifies several candidate drugs that may modulate gene expression in COVID-19 ARDS, including dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 is characterized by impaired interferon-stimulated gene (ISG) expression. The relationship between SARS-CoV-2 viral load and expression of ISGs is decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients reveals distinct immunological features of COVID-19 ARDS.
Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25040-5
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DOI: 10.1038/s41467-021-25040-5
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