Distinct pulmonary and systemic effects of dexamethasone in severe COVID-19

Lucile P. A. Neyton, Ravi K. Patel, Aartik Sarma, Andrew Willmore, Sidney C. Haller, Kirsten N. Kangelaris, Walter L. Eckalbar, David J. Erle, Matthew F. Krummel, Carolyn M. Hendrickson, Prescott G. Woodruff, Charles R. Langelier, Carolyn S. Calfee and Gabriela K. Fragiadakis ()
Additional contact information
Lucile P. A. Neyton: University of California
Ravi K. Patel: University of California San Francisco
Aartik Sarma: University of California
Andrew Willmore: University of California
Sidney C. Haller: University of California
Kirsten N. Kangelaris: University of California
Walter L. Eckalbar: University of California
David J. Erle: University of California
Matthew F. Krummel: University of California
Carolyn M. Hendrickson: University of California
Prescott G. Woodruff: University of California
Charles R. Langelier: Chan Zuckerberg Biohub
Carolyn S. Calfee: University of California
Gabriela K. Fragiadakis: University of California San Francisco

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Dexamethasone is the standard of care for critically ill patients with COVID-19, but the mechanisms by which it decreases mortality and its immunological effects in this setting are not understood. Here we perform bulk and single-cell RNA sequencing of samples from the lower respiratory tract and blood, and assess plasma cytokine profiling to study the effects of dexamethasone on both systemic and pulmonary immune cell compartments. In blood samples, dexamethasone is associated with decreased expression of genes associated with T cell activation, including TNFSFR4 and IL21R. We also identify decreased expression of several immune pathways, including major histocompatibility complex-II signaling, selectin P ligand signaling, and T cell recruitment by intercellular adhesion molecule and integrin activation, suggesting these are potential mechanisms of the therapeutic benefit of steroids in COVID-19. We identify additional compartment- and cell- specific differences in the effect of dexamethasone that are reproducible in publicly available datasets, including steroid-resistant interferon pathway expression in the respiratory tract, which may be additional therapeutic targets. In summary, we demonstrate compartment-specific effects of dexamethasone in critically ill COVID-19 patients, providing mechanistic insights with potential therapeutic relevance. Our results highlight the importance of studying compartmentalized inflammation in critically ill patients.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-49756-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49756-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-49756-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().