Kavli Affiliate: Martin Lindquist
| Authors: Maria Papadaki, Eleftherios Pavlos, Marc Dubourdeau, Vincent Bailif, Kamal Badirou, Ioanna-Evdokia Galani, Dimitris Papelis, Natalia Kamperi, Vasiliki Triantafyllia, Lena Siouti, Maria Salagianni, Maria Manioudaki, Nikolaos Paschalidis, Giannis Vatsellas, Evangelia Koukaki, Vasiliki Rapti, Dimitris Thanos, Nikoletta Rovina, Garyfallia Poulakou, Aurelie Cobat, Jean-Laurent Casanova, Constantin Tamvakopoulos and Evangelos Andreakos
| Summary:
Severe COVID-19, caused by SARS-CoV-2 infection, is 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 COVID-19 remains underexplored. By employing a holistic approach involving the analysis of white blood cell transcriptomes, targeted lipidomics, cytokine and immune cell profiling, across the spectrum of disease severity groups, including mild non-hospitalized patients and healthy individuals, we now show that LM networks are profoundly altered in COVID-19, correlate with inflammatory patterns, and stratify patients according to disease severity. Central to this are CYP450-derived LMs such as 20-HETE, lipid peroxidation metabolites such as iPF2a-VI, and lipoxygenase-derived LMs such as 12-HETE, all of which are major vasoactive mediators of inflammation. Among them, 20-HETE appears to be a promising prognostic biomarker for ICU admission and a potential therapeutic target for severe COVID-19 disease. Our study thus underscores the significance of LM networks in COVID-19 pathophysiology and sheds light into the broader mechanisms driving viral pneumonia in humans.