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Deep Phenotyping of the Lipidomic Response in COVID and non-COVID Sepsis.

Hu MengArjun SenguptaEmanuela RicciottiAntonijo MrčelaDivij MathewLiudmila L MazaleuskayaSoumita GhoshThomas G BrooksAlexandra P TurnerAlessa Soares SchanoskiNicholas F LahensAi Wen TanAshley WoolforkGreg GrantKatalin SusztakAndrew G LetiziaStuart C SealfonE John WherryKrzysztof LaudanskiAalim M WeljieNuala B MeyerGarret A FitzGerald
Published in: bioRxiv : the preprint server for biology (2023)
Lipids may influence cellular penetrance by pathogens and the immune response that they evoke. Here we find a broad based lipidomic storm driven predominantly by secretory (s) phospholipase A 2 (sPLA 2 ) dependent eicosanoid production occurs in patients with sepsis of viral and bacterial origin and relates to disease severity in COVID-19. Elevations in the cyclooxygenase (COX) products of arachidonic acid (AA), PGD 2 and PGI 2 , and the AA lipoxygenase (LOX) product, 12-HETE, and a reduction in the high abundance lipids, ChoE 18:3, LPC-O-16:0 and PC-O-30:0 exhibit relative specificity for COVID-19 amongst such patients, correlate with the inflammatory response and link to disease severity. Linoleic acid (LA) binds directly to SARS-CoV-2 and both LA and its di-HOME products reflect disease severity in COVID-19. AA and LA metabolites and LPC-O-16:0 linked variably to the immune response. These studies yield prognostic biomarkers and therapeutic targets for patients with sepsis, including COVID-19. An interactive purpose built interactive network analysis tool was developed, allowing the community to interrogate connections across these multiomic data and generate novel hypotheses.
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