Polyunsaturated fatty acid-derived lipid mediator patterns determine viral pneumonia severity and risk for critical COVID-19

• 成果类型: Article
• 署名作者: Papadaki, Maria; Pavlos, Eleftherios; Dubourdeau, Marc; Bailif, Vincent; Badirou, Kamal; Gely, Clemence A.; Galani, Ioanna-Evdokia; Papelis, Dimitris; Kamperi, Natalia; Triantafyllia, Vasiliki; Siouti, Eleni; Salagianni, Maria; Manioudaki, Maria; Paschalidis, Nikolaos; Vatsellas, Giannis; Koukaki, Evangelia; Rapti, Vasiliki; Thanos, Dimitris; Rovina, Nikoletta; Poulakou, Garyfallia; Cobat, Aurelie; Casanova, Jean-Laurent; Tamvakopoulos, Constantin; Andreakos, Evangelos
• 署名单位: Academy of Athens; University of Crete; Academy of Athens; Academy of Athens; Academy of Athens; National & Kapodistrian University of Athens; National & Kapodistrian University of Athens; Rockefeller University; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Necker-Enfants Malades - APHP; Howard Hughes Medical Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2534726123
• 发表日期: 2026-06-09
• 页码: e2534726123
• 关键词: lipid mediators; PUFAs; Covid-19; hyperinflammation; innate immune response; 20-HYDROXYEICOSATETRAENOIC ACID; angiotensin-ii; 20-HETE; LIPOXYGENASES; activation; oxidase

摘要

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 omega 6 and omega 3 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.