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

Autor: Eran Mick, Catherine DeVoe, Marina Sirota, Pratik Sinha, David J. Erle, Norma Neff, Michelle Tan, Alejandra Jauregui, Thomas Deiss, Paula Hayakawa Serpa, Angela Oliveira Pisco, Charles Langelier, Carolyn S. Calfee, Joseph L. DeRisi, Aleksandra Leligdowicz, Emily R. Siegel, Andrew Willmore, Matthew F. Krummel, Kirsten N. Kangelaris, Beth S. Zha, Alexandra Tsitsiklis, Jennifer G. Wilson, Rajani Ghale, Angela M Detweiler, Carolyn M. Hendrickson, Ashley Byrne, K. Mark Ansel, Farzad Moazed, Michael A. Matthay, Prescott G. Woodruff, Natasha Spottiswoode, Aartik Sarma, Stephanie A. Christenson
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
ARDS
COMET Consortium
General Physics and Astronomy
Cohort Studies
Gene expression
80 and over
2.1 Biological and endogenous factors
Aetiology
Acute inflammation
Lung
Acute Respiratory Distress Syndrome
Aged
80 and over
Respiratory Distress Syndrome
Multidisciplinary
Molecular medicine
Middle Aged
Trachea
medicine.anatomical_structure
Infectious Diseases
Viral pneumonia
Pneumonia & Influenza
Respiratory
Cytokines
Female
Viral load
Sequence Analysis
Adult
Science
Critical Illness
General Biochemistry
Genetics and Molecular Biology
Article
Proinflammatory cytokine
Rare Diseases
medicine
Genetics
Humans
Aged
business.industry
Sequence Analysis
RNA
SARS-CoV-2
Gene Expression Profiling
COVID-19
General Chemistry
Pneumonia
Translational research
medicine.disease
Gene expression profiling
Emerging Infectious Diseases
Viral infection
Case-Control Studies
Immunology
RNA
Cytokine storm
business
Respiratory tract
Zdroj: Nature Communications
Nature communications, vol 12, iss 1
Research Square
article-version (status) pre
article-version (number) 1
Nature Communications, Vol 12, Iss 1, Pp 1-10 (2021)
ISSN: 2041-1723
Popis: 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.
Here, the authors perform transcriptional profiling on tracheal aspirates of adults requiring mechanical ventilation for SARS-CoV2-induced acute respiratory distress syndrome (ARDS) and identify a dysregulated host response predicted to predicted to be potentially modulated by dexamethasone.
Databáze: OpenAIRE
Externí odkaz: