Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS
Authors: 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. ,   COMET Consortium, Abe-Jones Yumiko , Asthana Saurabh , Beagle Alexander , Bhakta Tanvi , Bhide Sharvari , Cai Cathy , Caldera Saharai , Calfee Carolyn , Calvo Maria , Carrillo Sidney , Cattamanchi Adithya , Chak Suzanna , Chan Vincent , Chew Nayvin , Christenson Stephanie , Collins Zachary , Combes Alexis , Courau Tristan , Darmanis Spyros , Erle David , Esmaili Armond , Fragiadakis Gabriela K. , Ghale Rajani , Giberson Jeremy , Gonzalez Ana , Serpa Paula Hayakawa , Hendrickson Carolyn , Hiam Kamir , Hu Kenneth , Huang Billy , Jauregui Alejandra , Jones Chayse , Jones Norman , Kangelaris Kirsten , Krummel Matthew , Kumar Nitasha , Kushnoor Divya , Lea Tasha , Lee Deanna , Lee David , Liu Kathleen D. , Liu Yale , Mahboob Salman , Matthay Michael , Milush Jeff , Muñoz-Sandoval Priscila , Nguyen Viet , Ortiz Gabe , Parada Randy , Phelps Maira , Pierce Logan , Prasad Priya , Rao Arjun , Rashid Sadeed , Reeder Gabriella , Rodriguez Nicklaus , Samad Bushra , Scarlet Diane , Shaw Cole , Shen Alan , Sigman Austin , Spitzer Matthew , Sun Yang , Sunshine Sara , Tang Kevin , Altamirano Luz Torres , Tsui Jessica , Tumurbaatar Erden , Turner Kathleen , Ward Alyssa , Willmore Andrew , Wilson Michael , Winkler Juliane , Withers Reese , Wong Kristine , Woodruff Prescott , Ye Jimmie , Yee Kimberly , Yu Michelle , Zha Shoshana , Zhan Jenny , Zhou Mingyue , Zhu Wandi S. , Hendrickson Carolyn M. , Kangelaris Kirsten N. , Krummel Matthew F. , Woodruff Prescott G. , Erle David J. , Calfee Carolyn S. , Langelier Charles R. 
Published: August 2021

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.