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

doi:10.1038/s41467-021-25040-5

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

Nat Commun. 2021 Aug 26;12(1):5152. doi: 10.1038/s41467-021-25040-5.

Authors

Aartik Sarma¹, Stephanie A Christenson^#¹, Ashley Byrne^#², Eran Mick^#^{1

2

3}, Angela Oliveira Pisco^#², Catherine DeVoe³, Thomas Deiss², Rajani Ghale^{1

3}, Beth Shoshana Zha¹, Alexandra Tsitsiklis³, Alejandra Jauregui¹, Farzad Moazed¹, Angela M Detweiler³, Natasha Spottiswoode⁴, Pratik Sinha⁵, Norma Neff², Michelle Tan², Paula Hayakawa Serpa³, Andrew Willmore¹, K Mark Ansel^{6

7}, Jennifer G Wilson⁸, Aleksandra Leligdowicz^{1

9

10}, Emily R Siegel¹¹, Marina Sirota¹², Joseph L DeRisi^{2

13}, Michael A Matthay^{1

10

14}; COMET Consortium; Carolyn M Hendrickson¹, Kirsten N Kangelaris⁴, Matthew F Krummel¹⁵, Prescott G Woodruff^{1

7}, David J Erle^{1

4

16

17}, Carolyn S Calfee^#^{1

10

14}, Charles R Langelier^#^{18

19}

Collaborators

COMET Consortium:
Yumiko Abe-Jones, Saurabh Asthana, Alexander Beagle, Tanvi Bhakta, Sharvari Bhide, Cathy Cai, Saharai Caldera, Carolyn Calfee, Maria Calvo, Sidney Carrillo, Adithya Cattamanchi, Suzanna Chak, Vincent Chan, Nayvin Chew, Stephanie Christenson, Zachary Collins, Alexis Combes, Tristan Courau, Spyros Darmanis, David Erle, Armond Esmaili, Gabriela K Fragiadakis, Rajani Ghale, Jeremy Giberson, Ana Gonzalez, Paula Hayakawa Serpa, Carolyn Hendrickson, Kamir Hiam, Kenneth Hu, Billy Huang, Alejandra Jauregui, Chayse Jones, Norman Jones, Kirsten Kangelaris, Matthew Krummel, Nitasha Kumar, Divya Kushnoor, Tasha Lea, Deanna Lee, David Lee, Kathleen D Liu, Yale Liu, Salman Mahboob, Michael Matthay, Jeff Milush, Priscila Muñoz-Sandoval, Viet Nguyen, Gabe Ortiz, Randy Parada, Maira Phelps, Logan Pierce, Priya Prasad, Arjun Rao, Sadeed Rashid, Gabriella Reeder, Nicklaus Rodriguez, Bushra Samad, Diane Scarlet, Cole Shaw, Alan Shen, Austin Sigman, Matthew Spitzer, Yang Sun, Sara Sunshine, Kevin Tang, Luz Torres Altamirano, Jessica Tsui, Erden Tumurbaatar, Kathleen Turner, Alyssa Ward, Andrew Willmore, Michael Wilson, Juliane Winkler, Reese Withers, Kristine Wong, Prescott Woodruff, Jimmie Ye, Kimberly Yee, Michelle Yu, Shoshana Zha, Jenny Zhan, Mingyue Zhou, Wandi S Zhu

Affiliations

¹ Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.
² Chan Zuckerberg Biohub, San Francisco, CA, USA.
³ Division of Infectious Diseases, University of California, San Francisco, CA, USA.
⁴ Department of Medicine, University of California, San Francisco, CA, USA.
⁵ Department of Anesthesia, Washington University, Saint Louis, MO, USA.
⁶ Department of Microbiology and Immunology, University of California, San Francisco, CA, USA.
⁷ Sandler Asthma Basic Research Center, University of California, San Francisco, CA, USA.
⁸ Department of Emergency Medicine, Stanford University, Palo Alto, CA, USA.
⁹ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Cardiovascular Research Institute, University of California, San Francisco, CA, USA.
¹¹ School of Medicine, University of California, San Francisco, CA, USA.
¹² Division of Rheumatology, University of California, San Francisco, CA, USA.
¹³ Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.
¹⁴ Department of Anesthesia, University of California, San Francisco, CA, USA.
¹⁵ Department of Pathology, University of California, San Francisco, CA, USA.
¹⁶ Lung Biology Center, University of California, San Francisco, CA, USA.
¹⁷ UCSF CoLabs, University of California, San Francisco, CA, USA.
¹⁸ Chan Zuckerberg Biohub, San Francisco, CA, USA. chaz.langelier@ucsf.edu.
¹⁹ Division of Infectious Diseases, University of California, San Francisco, CA, USA. chaz.langelier@ucsf.edu.

^# Contributed equally.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
COVID-19 / genetics*
COVID-19 / immunology
COVID-19 / virology
Case-Control Studies
Cohort Studies
Critical Illness
Cytokines / genetics
Cytokines / immunology
Female
Gene Expression Profiling
Humans
Male
Middle Aged
RNA / genetics*
RNA / metabolism
Respiratory Distress Syndrome / genetics*
Respiratory Distress Syndrome / immunology
Respiratory Distress Syndrome / virology
SARS-CoV-2 / physiology
Sequence Analysis, RNA
Trachea / immunology*

Substances

Cytokines
RNA

Abstract

Publication types

MeSH terms

Substances

Grants and funding