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

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Τίτλος: Polyunsaturated fatty acid-derived lipid mediator patterns determine viral pneumonia severity and risk for critical COVID-19.
Συγγραφείς: Papadaki M; Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece., Pavlos E; Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece.; Division of Basic Sciences, University of Crete Medical School, Heraklion 71110, Greece., Dubourdeau M; Ambiotis Société par Actions Simplifiée, Toulouse 31400, France., Bailif V; Ambiotis Société par Actions Simplifiée, Toulouse 31400, France., Badirou K; Ambiotis Société par Actions Simplifiée, Toulouse 31400, France., Gély CA; Ambiotis Société par Actions Simplifiée, Toulouse 31400, France., Galani IE; Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece., Papelis D; Division of Pharmacology-Pharmacotechnology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece., Kamperi N; Division of Pharmacology-Pharmacotechnology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece., Triantafyllia V; Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece., Siouti E; Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece., Salagianni M; Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece., Manioudaki M; Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece., Paschalidis N; Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece.; Greek Genome Center, Biomedical Research Foundation Academy of Athens, Athens 11527, Greece., Vatsellas G; Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece.; Greek Genome Center, Biomedical Research Foundation Academy of Athens, Athens 11527, Greece., Koukaki E; Intensive Care Unit, 1st Department of Respiratory Medicine, National and Kapodistrian University of Athens, Medical School, 'Sotiria' General Hospital of Chest Diseases, Athens 11527, Greece., Rapti V; 3rd Department of Internal Medicine, 'Sotiria' General Hospital of Chest Diseases, National and Kapodistrian University of Athens, Athens 11527, Greece., Thanos D; Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece.; Greek Genome Center, Biomedical Research Foundation Academy of Athens, Athens 11527, Greece., Rovina N; Intensive Care Unit, 1st Department of Respiratory Medicine, National and Kapodistrian University of Athens, Medical School, 'Sotiria' General Hospital of Chest Diseases, Athens 11527, Greece., Poulakou G; 3rd Department of Internal Medicine, 'Sotiria' General Hospital of Chest Diseases, National and Kapodistrian University of Athens, Athens 11527, Greece., Cobat A; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.; Laboratory of Human Genetics of Infectious Diseases, Inserm U1163, Paris 75015, France.; Paris Cité University, Imagine Institute, Paris 75015, France., Casanova JL; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.; Laboratory of Human Genetics of Infectious Diseases, Inserm U1163, Paris 75015, France.; Paris Cité University, Imagine Institute, Paris 75015, France.; Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, Assistante Publique-Hôpitaux de Paris, Paris 75015, France.; HHMI, New York, NY 10065., Tamvakopoulos C; Division of Pharmacology-Pharmacotechnology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece., Andreakos E; Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece.
Πηγή: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2026 Jun 09; Vol. 123 (23), pp. e2534726123. Date of Electronic Publication: 2026 Jun 01.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
Imprint Name(s): Original Publication: Washington, DC : National Academy of Sciences
Ιατρικοί όροι (MeSH): Fatty Acids, Unsaturated*/metabolism , COVID-19*, Hydroxyeicosatetraenoic Acids/blood ; Hydroxyeicosatetraenoic Acids/metabolism ; Cytokines/metabolism ; Fatty Acids, Omega-6/metabolism ; Fatty Acids, Omega-3/metabolism ; Humans ; SARS-CoV-2 ; Severity of Illness Index ; Male ; Female ; Lipidomics ; Inflammation
Περίληψη: 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.
Competing Interests: Competing interests statement:Evangelos Andreakos has received research support for unrelated research from BioNtech and Janssen. The remaining authors declare no competing interests.
Grant Information: 779295 EC | HORIZON EUROPE Framework Programme (Horizon Europe); 101057100 EC | HORIZON EUROPE Framework Programme (Horizon Europe); 1574 Hellenic Foundation for Research and Innovation (HFRI)
Contributed Indexing: Keywords: COVID-19; PUFAs; hyperinflammation; innate immune response; lipid mediators
Substance Nomenclature: 0 (Hydroxyeicosatetraenoic Acids)
0 (Cytokines)
0 (Fatty Acids, Unsaturated)
79551-86-3 (20-hydroxy-5,8,11,14-eicosatetraenoic acid)
0 (Fatty Acids, Omega-6)
0 (Fatty Acids, Omega-3)
Entry Date(s): Date Created: 20260601 Date Completed: 20260603 Latest Revision: 20260730
Update Code: 20260730
PubMed Central ID: PMC13250500
DOI: 10.1073/pnas.2534726123
PMID: 42224585
Βάση Δεδομένων: MEDLINE
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  Data: <searchLink fieldCode="JN" term="%227505876%22">Proceedings of the National Academy of Sciences of the United States of America</searchLink> [Proc Natl Acad Sci U S A] 2026 Jun 09; Vol. 123 (23), pp. e2534726123. <i>Date of Electronic Publication: </i>2026 Jun 01.
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  Data: <searchLink fieldCode="MM" term="%22Fatty+Acids%2C+Unsaturated%22">Fatty Acids, Unsaturated*</searchLink>/<searchLink fieldCode="MM" term="%22Fatty+Acids%2C+Unsaturated+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22COVID-19%22">COVID-19*</searchLink><br /><searchLink fieldCode="MH" term="%22Hydroxyeicosatetraenoic+Acids%22">Hydroxyeicosatetraenoic Acids</searchLink>/<searchLink fieldCode="MH" term="%22Hydroxyeicosatetraenoic+Acids+blood%22">blood</searchLink> ; <searchLink fieldCode="MH" term="%22Hydroxyeicosatetraenoic+Acids%22">Hydroxyeicosatetraenoic Acids</searchLink>/<searchLink fieldCode="MH" term="%22Hydroxyeicosatetraenoic+Acids+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Cytokines%22">Cytokines</searchLink>/<searchLink fieldCode="MH" term="%22Cytokines+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Fatty+Acids%2C+Omega-6%22">Fatty Acids, Omega-6</searchLink>/<searchLink fieldCode="MH" term="%22Fatty+Acids%2C+Omega-6+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Fatty+Acids%2C+Omega-3%22">Fatty Acids, Omega-3</searchLink>/<searchLink fieldCode="MH" term="%22Fatty+Acids%2C+Omega-3+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22SARS-CoV-2%22">SARS-CoV-2</searchLink> ; <searchLink fieldCode="MH" term="%22Severity+of+Illness+Index%22">Severity of Illness Index</searchLink> ; <searchLink fieldCode="MH" term="%22Male%22">Male</searchLink> ; <searchLink fieldCode="MH" term="%22Female%22">Female</searchLink> ; <searchLink fieldCode="MH" term="%22Lipidomics%22">Lipidomics</searchLink> ; <searchLink fieldCode="MH" term="%22Inflammation%22">Inflammation</searchLink>
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  Data: 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.
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  Data: Competing interests statement:Evangelos Andreakos has received research support for unrelated research from BioNtech and Janssen. The remaining authors declare no competing interests.
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  Data: 779295 EC | HORIZON EUROPE Framework Programme (Horizon Europe); 101057100 EC | HORIZON EUROPE Framework Programme (Horizon Europe); 1574 Hellenic Foundation for Research and Innovation (HFRI)
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