COVID-19 ARDS: dysregulated host response differs from cytokine storm, may be modified by dexamethasone

 Aartik Sarma,  

View ORCID ProfileStephanie A. Christenson,  View ORCID ProfileEran Mick, Catherine DeVoe, Thomas Deiss, Angela Oliveira Pisco, Rajani Ghale, Alejandra Jauregui, Ashley Byrne, Farzad Moazed, Natasha Spottiswoode, Pratik Sinha,  View ORCID ProfileBeth Shoshana Zha, Paula Hayakawa Serpa,  View ORCID ProfileK. Mark Ansel, Jennifer G. Wilson,  View ORCID ProfileAleksandra Leligdowicz, Emily R. Siegel,  View ORCID ProfileMarina Sirota, Joseph L. DeRisi, Michael A. Matthay, COMET Consortium, Carolyn M. Hendrickson,  View ORCID ProfileKirsten N. Kangelaris, Matthew Krummel, Prescott G. Woodruff,  View ORCID ProfileDavid J. Erle, Carolyn S. Calfee, Charles R. Langelier

doi: https://doi.org/10.1101/2020.12.28.20248552

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2020.12.28.20248552v1.full.pdf

Abstract

We performed comparative lower respiratory tract transcriptional profiling of 52 critically ill patients with ARDS from COVID-19 or other etiologies, or without ARDS. We found no evidence of cytokine storm but instead observed complex host response dysregulation driven by genes with non-canonical roles in inflammation and immunity that were predicted to be modulated by dexamethasone. Compared to other viral ARDS, COVID-19 was characterized by impaired interferon-stimulated gene expression.

Competing Interest Statement

Dr. Christenson reports personal fees from AstraZeneca, personal fees from GlaxoSmithKline, personal fees from Amgen, personal fees from Glenmark, personal fees from Sunovion, personal fees from Genentech, personal fees from UpToDate, outside the submitted work. Dr. Sirota reports personal fees from TwoXAR. Dr. Matthay reports grants from Roche-Genentech, personal fees from Citius Pharmaceuticals, personal fees from Novartis Pharmaceutricals, outside the submitted work. Dr. Woodruff reports grants from Genentech, personal fees from Sanofi, personal fees from Regeneron, personal fees from Glenmark Pharmaceuticals, personal fees from Theravance, personal fees from NGM Pharma, outside the submitted work. Dr. Calfee reports grants and personal fees from Roche/Genentech, grants and personal fees from Bayer, personal fees from Quark Pharmaceuticals, personal fees from Prometic, personal fees from Gen1e Life Sciences, personal fees from Vasomune, grants from Quantum Leap Healthcare Collaborative, outside the submitted work. The remaining authors declare no competing interests.

Funding Statement

NIH R35 HL140026 (CSC), NIH/NIAID U19 AI1077439 (DE), NHLBI K23HL138461-01A1 (CL), K24HL137013 (PGW), F32 HL151117 (AS), Chan Zuckerberg Biohub (AOP, AB, PHS, AK, JLD), Philanthropic contributions from: Mark and Carrie Casey, Julia and Kevin Hartz, Carl Kawaja and Wendy Holcombe, Eric Keisman and Linda Nevin, Martin and Leesa Romo, Three Sisters Foundation, Diana Wagner, Jerry Yang and Akiko Yamazaki.

https://www.medrxiv.org/content/10.1101/2020.12.28.20248552v1