Evangelos Andreakos and colleagues recently published a study in the Proceedings of the National Academy of Sciences of USA (PNAS)

A new study by Evangelos Andreakos, Constantin Tamvakopoulos, Maria Papadaki and colleagues published in Proceedings of the National Academy of Sciences (PNAS) provides important insights into the biological mechanisms that determine why some patients develop severe viral pneumonia while others experience milder or even asymptomatic disease.

While research on viral pneumonia, including COVID-19, has largely focused on immune cells and inflammatory cytokines—the so-called “cytokine storm”—much less is known about the role of lipid mediators, a class of bioactive molecules that are critical regulators of both the initiation and resolution of inflammation. Derived from omega-3 and omega-6 polyunsaturated fatty acids, these molecules have long been recognized as key orchestrators of immune responses, yet their contribution to viral pneumonia has remained poorly understood.

By combining state-of-the-art lipidomics, deep immune profiling, and clinical analyses in patients spanning the full spectrum of COVID-19 severity, the researchers identified distinct molecular signatures associated with either mild or severe disease. The study also uncovered lipid mediators with strong predictive value, most notably 20-HETE, which emerged as a promising biomarker of disease severity and progression.

The findings highlight lipid mediators as a previously underappreciated component of the inflammatory response in viral pneumonia and suggest that they may actively contribute to disease outcomes. Beyond advancing our understanding of COVID-19, this work opens new opportunities for the development of biomarkers and therapeutic strategies for viral pneumonia and other severe respiratory infections.

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

Maria Papadaki, Eleftherios Pavlos, Marc Dubourdeau, Vincent Bailif, Kamal Badirou, Clémence A Gély, Ioanna-Evdokia Galani, Dimitris Papelis, Natalia Kamperi, Vasiliki Triantafyllia, Eleni Siouti, Maria Salagianni, Maria Manioudaki, Nikolaos Paschalidis, Giannis Vatsellas, Evangelia Koukaki, Vasiliki Rapti, Dimitris Thanos, Nikoletta Rovina, Garyfallia Poulakou, Aurélie Cobat, Jean-Laurent Casanova, Constantin Tamvakopoulos, Evangelos Andreakos. Polyunsaturated fatty acid-derived lipid mediator patterns determine viral pneumonia severity and risk for critical COVID-19. Proc Natl Acad Sci USA. 2026 Jun 9;123(23):e2534726123

Pubmed