Polyunsaturated fatty acid–derived lipid mediator patterns determine viral pneumonia severity and risk for critical COVID-19
Abstract
Severe respiratory infections such as COVID-19 are characterized by excessive inflammation leading to the development of pneumonia and acute respiratory distress syndrome. Bioactive lipid mediators (LMs) derived from ω6 and ω3 polyunsaturated fatty acids are central to the regulation of inflammation, controlling both its initiation and resolution. Still, their role in viral infections remains underexplored. By employing a holistic approach involving the analysis of white blood cell transcriptomes, targeted lipidomics, cytokine and immune cell profiling, we now show that LM patterns around hospital admission are profoundly altered in COVID-19, correlate with inflammatory responses, and stratify patients according to disease severity. Central to this are CYP450-derived LMs, such as 20-HETE, and lipoxygenase- or nonenzymatic-associated LMs such as 15-HETE, both exhibiting vasoactive function, along with lipid peroxidation metabolites such as 10-HDOHE. Among them, increased 20-HETE appears to be a promising prognostic biomarker for ICU admission and a potential therapeutic target for severe COVID-19 disease. Our study emphasizes the importance of LM patterns in COVID-19 pathophysiology and sheds light into the broader immune mechanisms beyond cytokines driving viral pneumonia in humans.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (24)
Maria Papadaki
Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens
Eleftherios Pavlos
Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens
Marc Dubourdeau
Ambiotis Société par Actions Simplifiée
Vincent Bailif
Ambiotis Société par Actions Simplifiée
Kamal Badirou
Ambiotis Société par Actions Simplifiée
Clémence A. Gély
Ambiotis Société par Actions Simplifiée
Ioanna-Evdokia Galani
Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens
Dimitris Papelis
Division of Pharmacology-Pharmacotechnology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens
Natalia Kamperi
Division of Pharmacology-Pharmacotechnology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens
Vasiliki Triantafyllia
Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens
Eleni Siouti
Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens
Maria Salagianni
Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens
Maria Manioudaki
Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens
Nikolaos Paschalidis
Center of Basic Research, Biomedical Research Foundation of the Academy of Athens
Giannis Vatsellas
Center of Basic Research, Biomedical Research Foundation of the Academy of Athens
Evangelia Koukaki
Intensive Care Unit, 1st Department of Respiratory Medicine, National and Kapodistrian University of Athens, Medical School, ‘Sotiria’ General Hospital of Chest Diseases
Vasiliki Rapti
3rd Department of Internal Medicine, “Sotiria” General Hospital of Chest Diseases, National and Kapodistrian University of Athens
Dimitris Thanos
Center of Basic Research, Biomedical Research Foundation of the Academy of Athens
Nikoletta Rovina
Intensive Care Unit, 1st Department of Respiratory Medicine, National and Kapodistrian University of Athens, Medical School, ‘Sotiria’ General Hospital of Chest Diseases
Garyfallia Poulakou
3rd Department of Internal Medicine, “Sotiria” General Hospital of Chest Diseases, National and Kapodistrian University of Athens
Aurélie Cobat
St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University
Jean-Laurent Casanova
Constantin Tamvakopoulos
Division of Pharmacology-Pharmacotechnology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens
Evangelos Andreakos
Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens