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

Autor: Neyton LPA; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA., Patel RK; UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA., Sarma A; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA., Willmore A; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA., Haller SC; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA., Kangelaris KN; Division of Hospital Medicine, University of California, San Francisco, CA, USA., Eckalbar WL; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.; UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA., Erle DJ; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.; UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA.; Department of Medicine, University of California, San Francisco, CA, USA.; Lung Biology Center, University of California, San Francisco, CA, USA., Krummel MF; Department of Pathology, University of California, San Francisco, CA, USA., Hendrickson CM; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA., Woodruff PG; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA., Langelier CR; Chan Zuckerberg Biohub, San Francisco, CA, USA.; Division of Infectious Diseases, University of California, San Francisco, CA, USA., Calfee CS; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA, USA.; Department of Medicine, University of California, San Francisco, CA, USA.; Department of Anesthesia, University of California, San Francisco, CA, USA., Fragiadakis GK; UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA. gabriela.fragiadakis@ucsf.edu.; Division of Rheumatology, University of California, San Francisco, CA, USA. gabriela.fragiadakis@ucsf.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jun 28; Vol. 15 (1), pp. 5483. Date of Electronic Publication: 2024 Jun 28.
DOI: 10.1038/s41467-024-49756-2
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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