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 Jáuregui, 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, Yumiko Abe‐Jones, Saurabh Asthana, Alexander J. Beagle, Tanvi Bhakta, Sharvari Bhide, Cathy Cai, Saharai Caldera, Carolyn S. Calfee, Maria Calvo, Sidney Carrillo, Adithya Cattamanchi, Suzanna Chak, Vincent Chan, Nayvin W. Chew, Stephanie A. Christenson, Zachary Collins, Alexis J. Combes, Tristan Courau, Spyros Darmanis, David J. Erle, Armond Esmaili, Gabriela K. Fragiadakis, Rajani Ghale, Jeremy Giberson, Ana Gonzalez, Paula Hayakawa Serpa, Carolyn M. Hendrickson, Kamir Hiam, Kenneth H. Hu, Billy Huang, Alejandra Jáuregui, Chayse Jones, Norman G. Jones, Kirsten N. Kangelaris, Matthew F. Krummel, Nitasha Kumar, Divya Kushnoor, Tasha Lea, Deanna Lee, David Lee, Kathleen D. Liu, Yale Liu, Salman Mahboob, Michael A. Matthay, Jeff Milush, Priscila Muñoz-Sandoval, Nguyễn Hoàng Việt, Gabe Ortiz, Randy Parada, Maíra Phelps, Logan Pierce, Priya A. Prasad, Arjun A. Rao, Sadeed Rashid, Gabriella C. Reeder, Nicklaus Rodriguez, Bushra Samad, Diane Scarlet, Cole Shaw, Alan Shen, Austin Sigman, Matthew H. Spitzer, Yang Sun, Sara Sunshine, Kevin Tang, Luz Torres Altamirano, Jessica Tsui, Erden Tumurbaatar, Kathleen Turner, Alyssa Ward, Andrew Willmore, Michael R. Wilson, Juliane Winkler, Reese Withers
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.