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

Author

Listed:
  • Aartik Sarma

    (University of California)

  • Stephanie A. Christenson

    (University of California)

  • Ashley Byrne

    (Chan Zuckerberg Biohub)

  • Eran Mick

    (University of California
    Chan Zuckerberg Biohub
    University of California)

  • Angela Oliveira Pisco

    (Chan Zuckerberg Biohub)

  • Catherine DeVoe

    (University of California)

  • Thomas Deiss

    (Chan Zuckerberg Biohub)

  • Rajani Ghale

    (University of California
    University of California)

  • Beth Shoshana Zha

    (University of California)

  • Alexandra Tsitsiklis

    (University of California)

  • Alejandra Jauregui

    (University of California)

  • Farzad Moazed

    (University of California)

  • Angela M. Detweiler

    (University of California)

  • Natasha Spottiswoode

    (University of California)

  • Pratik Sinha

    (Washington University)

  • Norma Neff

    (Chan Zuckerberg Biohub)

  • Michelle Tan

    (Chan Zuckerberg Biohub)

  • Paula Hayakawa Serpa

    (University of California)

  • Andrew Willmore

    (University of California)

  • K. Mark Ansel

    (University of California
    University of California)

  • Jennifer G. Wilson

    (Stanford University)

  • Aleksandra Leligdowicz

    (University of California
    University of Toronto
    University of California)

  • Emily R. Siegel

    (University of California)

  • Marina Sirota

    (University of California)

  • Joseph L. DeRisi

    (Chan Zuckerberg Biohub
    University of California)

  • Michael A. Matthay

    (University of California
    University of California
    University of California)

  • Carolyn M. Hendrickson

    (University of California)

  • Kirsten N. Kangelaris

    (University of California)

  • Matthew F. Krummel

    (University of California)

  • Prescott G. Woodruff

    (University of California
    University of California)

  • David J. Erle

    (University of California
    University of California
    University of California
    University of California)

  • Carolyn S. Calfee

    (University of California
    University of California
    University of California)

  • Charles R. Langelier

    (Chan Zuckerberg Biohub
    University of California)

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.

Suggested Citation

  • Aartik Sarma & Stephanie A. Christenson & Ashley Byrne & Eran Mick & Angela Oliveira Pisco & Catherine DeVoe & Thomas Deiss & Rajani Ghale & Beth Shoshana Zha & Alexandra Tsitsiklis & Alejandra Jaureg, 2021. "Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25040-5
    DOI: 10.1038/s41467-021-25040-5
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    Cited by:

    1. Sara Sunshine & Andreas S. Puschnik & Joseph M. Replogle & Matthew T. Laurie & Jamin Liu & Beth Shoshana Zha & James K. Nuñez & Janie R. Byrum & Aidan H. McMorrow & Matthew B. Frieman & Juliane Winkle, 2023. "Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Natasha Spottiswoode & Alexandra Tsitsiklis & Victoria T. Chu & Hoang Van Phan & Catherine DeVoe & Christina Love & Rajani Ghale & Joshua Bloomstein & Beth Shoshana Zha & Cole P. Maguire & Abigail Gla, 2024. "Microbial dynamics and pulmonary immune responses in COVID-19 secondary bacterial pneumonia," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Lucile P. A. Neyton & Ravi K. Patel & Aartik Sarma & Andrew Willmore & Sidney C. Haller & Kirsten N. Kangelaris & Walter L. Eckalbar & David J. Erle & Matthew F. Krummel & Carolyn M. Hendrickson & Pre, 2024. "Distinct pulmonary and systemic effects of dexamethasone in severe COVID-19," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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