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COVID-19 ARDS is characterized by a dysregulated host response that differs from cytokine storm and is modified by dexamethasone.


ABSTRACT: We performed comparative lower respiratory tract transcriptional profiling of 52 critically ill patients with the acute respiratory distress syndrome (ARDS) from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a cytokine storm, we observed reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS was characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity that were predicted to be modulated by dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 was characterized by impaired interferon-stimulated gene expression (ISG). We found that the relationship between SARS-CoV-2 viral load and expression of ISGs was 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 with COVID-19 ARDS did not demonstrate cytokine storm but instead revealed a unique and dysregulated host response predicted to be modified by dexamethasone.

SUBMITTER: Sarma A 

PROVIDER: S-EPMC7814832 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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COVID-19 ARDS is characterized by a dysregulated host response that differs from cytokine storm and is modified by dexamethasone.

Sarma Aartik A   Christenson Stephanie A SA   Mick Eran E   DeVoe Catherine C   Deiss Thomas T   Pisco Angela Oliveira AO   Ghale Rajani R   Jauregui Alejandra A   Byrne Ashley A   Moazed Farzad F   Spottiswoode Natasha N   Sinha Pratik P   Zha Beth Shoshana BS   Neff Norma N   Tan Michelle M   Serpa Paula Hayakawa PH   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  

Research square 20210114


We performed comparative lower respiratory tract transcriptional profiling of 52 critically ill patients with the acute respiratory distress syndrome (ARDS) from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a cytokine storm, we observed reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS was characterized by a dysregulated host response with increased PTEN signaling and elevated expression of gen  ...[more]

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