Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS.
Aartik Sarma, Stephanie A Christenson, Ashley Byrne, Eran Mick, Angela Oliveira Pisco, Catherine DeVoe, Thomas Deiss, Rajani Ghale, Beth Shoshana Zha, Alexandra Tsitsiklis, Alejandra Jauregui, Farzad Moazed, Angela M Detweiler, Natasha Spottiswoode, Pratik Sinha, Norma Neff, Michelle Tan, Paula Hayakawa Serpa, Andrew Willmore, K Mark Ansel, Jennifer G Wilson, Aleksandra Leligdowicz, Emily R Siegel, Marina Sirota, Joseph L DeRisi, Michael A Matthay, COMET Consortium, Carolyn M Hendrickson, Kirsten N Kangelaris, Matthew F Krummel, Prescott G Woodruff, David J Erle, Carolyn S Calfee, Charles R Langelier
Author Information
Aartik Sarma: Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA. ORCID
Stephanie A Christenson: Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
Ashley Byrne: Chan Zuckerberg Biohub, San Francisco, CA, USA. ORCID
Eran Mick: Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA. ORCID
Angela Oliveira Pisco: Chan Zuckerberg Biohub, San Francisco, CA, USA. ORCID
Catherine DeVoe: Division of Infectious Diseases, University of California, San Francisco, CA, USA.
Thomas Deiss: Chan Zuckerberg Biohub, San Francisco, CA, USA.
Rajani Ghale: Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
Beth Shoshana Zha: Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
Alexandra Tsitsiklis: Division of Infectious Diseases, University of California, San Francisco, CA, USA. ORCID
Alejandra Jauregui: Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
Farzad Moazed: Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
Angela M Detweiler: Division of Infectious Diseases, University of California, San Francisco, CA, USA.
Natasha Spottiswoode: Department of Medicine, University of California, San Francisco, CA, USA.
Pratik Sinha: Department of Anesthesia, Washington University, Saint Louis, MO, USA.
Norma Neff: Chan Zuckerberg Biohub, San Francisco, CA, USA. ORCID
Michelle Tan: Chan Zuckerberg Biohub, San Francisco, CA, USA.
Paula Hayakawa Serpa: Division of Infectious Diseases, University of California, San Francisco, CA, USA.
Andrew Willmore: Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
K Mark Ansel: Department of Microbiology and Immunology, University of California, San Francisco, CA, USA. ORCID
Jennifer G Wilson: Department of Emergency Medicine, Stanford University, Palo Alto, CA, USA.
Aleksandra Leligdowicz: Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
Emily R Siegel: School of Medicine, University of California, San Francisco, CA, USA.
Marina Sirota: Division of Rheumatology, University of California, San Francisco, CA, USA.
Joseph L DeRisi: Chan Zuckerberg Biohub, San Francisco, CA, USA.
Michael A Matthay: Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA. ORCID
Carolyn M Hendrickson: Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
Kirsten N Kangelaris: Department of Medicine, University of California, San Francisco, CA, USA.
Matthew F Krummel: Department of Pathology, University of California, San Francisco, CA, USA.
Prescott G Woodruff: Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
David J Erle: Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA. ORCID
Carolyn S Calfee: Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
Charles R Langelier: Chan Zuckerberg Biohub, San Francisco, CA, USA. chaz.langelier@ucsf.edu. ORCID
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.
References
N Engl J Med. 2021 Apr 22;384(16):1491-1502
[PMID: 33631065]
