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Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS.

Authors :
Sarma A
Christenson SA
Byrne A
Mick E
Pisco AO
DeVoe C
Deiss T
Ghale R
Zha BS
Tsitsiklis A
Jauregui A
Moazed F
Detweiler AM
Spottiswoode N
Sinha P
Neff N
Tan M
Serpa PH
Willmore A
Ansel KM
Wilson JG
Leligdowicz A
Siegel ER
Sirota M
DeRisi JL
Matthay MA
Hendrickson CM
Kangelaris KN
Krummel MF
Woodruff PG
Erle DJ
Calfee CS
Langelier CR
Source :
Nature communications [Nat Commun] 2021 Aug 26; Vol. 12 (1), pp. 5152. Date of Electronic Publication: 2021 Aug 26.
Publication Year :
2021

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.<br /> (© 2021. The Author(s).)

Details

Language :
English
ISSN :
2041-1723
Volume :
12
Issue :
1
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
34446707
Full Text :
https://doi.org/10.1038/s41467-021-25040-5