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

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.

SUBMITTER: Sarma A

PROVIDER: S-EPMC8390461 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Sarma Aartik A Christenson Stephanie A SA Byrne Ashley A Mick Eran E Pisco Angela Oliveira AO DeVoe Catherine C Deiss Thomas T Ghale Rajani R Zha Beth Shoshana BS Tsitsiklis Alexandra A Jauregui Alejandra A Moazed Farzad F Detweiler Angela M AM Spottiswoode Natasha N Sinha Pratik P Neff Norma N Tan Michelle M Serpa Paula Hayakawa PH Willmore Andrew A Ansel K Mark KM Wilson Jennifer G JG Leligdowicz Aleksandra A Siegel Emily R ER Sirota Marina M DeRisi Joseph L JL Matthay Michael A MA Hendrickson Carolyn M CM Kangelaris Kirsten N KN Krummel Matthew F MF Woodruff Prescott G PG Erle David J DJ Calfee Carolyn S CS Langelier Charles R CR

Nature communications 20210826 1

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 ...[more]

PMID: 34446707

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

Publications

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

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