Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS
Aartik Sarma(University of California, San Francisco), Stephanie A. Christenson(University of California, San Francisco), Ashley Byrne(Chan Zuckerberg Initiative (United States)), Eran Mick(University of California, San Francisco), Angela Oliveira Pisco(Chan Zuckerberg Initiative (United States)), Catherine DeVoe(University of California, San Francisco), Thomas Deiss(Chan Zuckerberg Initiative (United States)), Rajani Ghale(University of California, San Francisco), Beth Shoshana Zha(University of California, San Francisco), Alexandra Tsitsiklis(University of California, San Francisco), Alejandra Jáuregui(University of California, San Francisco), Farzad Moazed(University of California, San Francisco), Angela M. Detweiler(University of California, San Francisco), Natasha Spottiswoode(University of California, San Francisco), Pratik Sinha(Washington University in St. Louis), Norma Neff(Chan Zuckerberg Initiative (United States)), Michelle Tan(Chan Zuckerberg Initiative (United States)), Paula Hayakawa Serpa(University of California, San Francisco), Andrew Willmore(University of California, San Francisco), K. Mark Ansel(University of California, San Francisco), Jennifer G. Wilson(Stanford University), Aleksandra Leligdowicz(University of California, San Francisco), Emily R. Siegel(University of California, San Francisco), Marina Sirota(University of California, San Francisco), Joseph L. DeRisi(University of California, San Francisco), Michael A. Matthay(University of California, San Francisco), Yumiko Abe‐Jones(University of California, San Francisco), Saurabh Asthana(University of California, San Francisco), Alexander J. Beagle(University of California, San Francisco), Tanvi Bhakta(San Francisco General Hospital), Sharvari Bhide(University of California, San Francisco), Cathy Cai(University of California, San Francisco), Saharai Caldera(University of California, San Francisco), Carolyn S. Calfee(University of California, San Francisco), Maria Calvo(University of California, San Francisco), Sidney Carrillo(University of California, San Francisco), Adithya Cattamanchi(University of California, San Francisco), Suzanna Chak(University of California, San Francisco), Vincent Chan(University of California, San Francisco), Nayvin W. Chew(University of California, San Francisco), Stephanie A. Christenson(University of California, San Francisco), Zachary Collins(University of California, San Francisco), Alexis J. Combes(University of California, San Francisco), Tristan Courau(University of California, San Francisco), Spyros Darmanis, David J. Erle(University of California, San Francisco), Armond Esmaili(University of California, San Francisco), Gabriela K. Fragiadakis(University of California, San Francisco), Rajani Ghale(University of California, San Francisco), Jeremy Giberson(University of California, San Francisco), Ana Gonzalez(University of California, San Francisco), Paula Hayakawa Serpa(University of California, San Francisco), Carolyn M. Hendrickson(University of California, San Francisco), Kamir Hiam(University of California, San Francisco), Kenneth H. Hu(University of California, San Francisco), Billy Huang(University of California, San Francisco), Alejandra Jáuregui(University of California, San Francisco), Chayse Jones(University of California, San Francisco), Norman G. Jones(University of California, San Francisco), Kirsten N. Kangelaris(University of California, San Francisco), Matthew F. Krummel(University of California, San Francisco), Nitasha Kumar(University of California, San Francisco), Divya Kushnoor(University of California, San Francisco), Tasha Lea(University of California, San Francisco), Deanna Lee(University of California, San Francisco), David Lee(University of California, San Francisco), Kathleen D. Liu(University of California, San Francisco), Yale Liu(University of California, San Francisco), Salman Mahboob(University of California, San Francisco), Michael A. Matthay(University of California, San Francisco), Jeff Milush(University of California, San Francisco), Priscila Muñoz-Sandoval(University of California, San Francisco), Nguyễn Hoàng Việt(University of California, San Francisco), Gabe Ortiz(San Francisco General Hospital), Randy Parada(University of California, San Francisco), Maíra Phelps(Chan Zuckerberg Initiative (United States)), Logan Pierce(University of California, San Francisco), Priya A. Prasad(University of California, San Francisco), Arjun A. Rao(University of California, San Francisco), Sadeed Rashid(University of California, San Francisco), Gabriella C. Reeder(University of California, San Francisco), Nicklaus Rodriguez(University of California, San Francisco), Bushra Samad(University of California, San Francisco), Diane Scarlet(San Francisco General Hospital), Cole Shaw(University of California, San Francisco), Alan Shen(University of California, San Francisco), Austin Sigman(University of California, San Francisco), Matthew H. Spitzer(University of California, San Francisco), Yang Sun(University of California, San Francisco), Sara Sunshine(University of California, San Francisco), Kevin Tang(University of California, San Francisco), Luz Torres Altamirano(University of California, San Francisco), Jessica Tsui(University of California, San Francisco), Erden Tumurbaatar(University of California, San Francisco), Kathleen Turner(University of California, San Francisco), Alyssa Ward(University of California, San Francisco), Andrew Willmore(University of California, San Francisco), Michael R. Wilson(University of California, San Francisco), Juliane Winkler(University of California, San Francisco), Reese Withers(University of California, San Francisco), Kristine Wong(University of California, San Francisco), Prescott G. Woodruff(University of California, San Francisco), Chun Ye(University of California, San Francisco), Kimberly Yee(University of California, San Francisco), Michelle Yu(University of California, San Francisco), Beth Shoshana Zha(University of California, San Francisco), Jenny Zhan(University of California, San Francisco), Mingyue Zhou(University of California, San Francisco), Wandi S. Zhu(University of California, San Francisco), Carolyn M. Hendrickson(University of California, San Francisco), Kirsten N. Kangelaris(University of California, San Francisco), Matthew F. Krummel(University of California, San Francisco), Prescott G. Woodruff(University of California, San Francisco), David J. Erle(University of California, San Francisco), Carolyn S. Calfee(University of California, San Francisco), Charles Langelier(University of California, San Francisco)
Cited by 79Open Access
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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