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Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS.
Sarma, Aartik; Christenson, Stephanie A; Byrne, Ashley; Mick, Eran; Pisco, Angela Oliveira; DeVoe, Catherine; Deiss, Thomas; Ghale, Rajani; Zha, Beth Shoshana; Tsitsiklis, Alexandra; Jauregui, Alejandra; Moazed, Farzad; Detweiler, Angela M; Spottiswoode, Natasha; Sinha, Pratik; Neff, Norma; Tan, Michelle; Serpa, Paula Hayakawa; Willmore, Andrew; Ansel, K Mark; Wilson, Jennifer G; Leligdowicz, Aleksandra; Siegel, Emily R; Sirota, Marina; DeRisi, Joseph L; Matthay, Michael A; Hendrickson, Carolyn M; Kangelaris, Kirsten N; Krummel, Matthew F; Woodruff, Prescott G; Erle, David J; Calfee, Carolyn S; Langelier, Charles R.
Afiliação
  • Sarma A; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
  • Christenson SA; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
  • Byrne A; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Mick E; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
  • Pisco AO; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • DeVoe C; Division of Infectious Diseases, University of California, San Francisco, CA, USA.
  • Deiss T; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Ghale R; Division of Infectious Diseases, University of California, San Francisco, CA, USA.
  • Zha BS; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Tsitsiklis A; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
  • Jauregui A; Division of Infectious Diseases, University of California, San Francisco, CA, USA.
  • Moazed F; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
  • Detweiler AM; Division of Infectious Diseases, University of California, San Francisco, CA, USA.
  • Spottiswoode N; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
  • Sinha P; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
  • Neff N; Division of Infectious Diseases, University of California, San Francisco, CA, USA.
  • Tan M; Department of Medicine, University of California, San Francisco, CA, USA.
  • Serpa PH; Department of Anesthesia, Washington University, Saint Louis, MO, USA.
  • Willmore A; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Ansel KM; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Wilson JG; Division of Infectious Diseases, University of California, San Francisco, CA, USA.
  • Leligdowicz A; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
  • Siegel ER; Department of Microbiology and Immunology, University of California, San Francisco, CA, USA.
  • Sirota M; Sandler Asthma Basic Research Center, University of California, San Francisco, CA, USA.
  • DeRisi JL; Department of Emergency Medicine, Stanford University, Palo Alto, CA, USA.
  • Matthay MA; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
  • Hendrickson CM; Cardiovascular Research Institute, University of California, San Francisco, CA, USA.
  • Kangelaris KN; School of Medicine, University of California, San Francisco, CA, USA.
  • Krummel MF; Division of Rheumatology, University of California, San Francisco, CA, USA.
  • Woodruff PG; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Erle DJ; Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.
  • Calfee CS; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
  • Langelier CR; Cardiovascular Research Institute, University of California, San Francisco, CA, USA.
Nat Commun ; 12(1): 5152, 2021 08 26.
Article em En | MEDLINE | ID: mdl-34446707
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Síndrome do Desconforto Respiratório / Traqueia / RNA / COVID-19 Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Síndrome do Desconforto Respiratório / Traqueia / RNA / COVID-19 Idioma: En Ano de publicação: 2021 Tipo de documento: Article