{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T23:15:58Z","timestamp":1761693358236,"version":"build-2065373602"},"reference-count":41,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE31928"],"award-info":[{"award-number":["R01DE31928"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["U54GM115428","P20GM104357","P20GM121334"],"award-info":[{"award-number":["U54GM115428","P20GM104357","P20GM121334"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,5,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Many questions remain unanswered regarding the implication of genetics and lipid metabolites with severe SARS\u2010CoV\u20102 infections. We performed bulk RNA\u2010seq and a total fatty acid panel analysis on PBMCs and plasma collected from 10 infected and 10 uninfected patients. Univariate comparison of lipid metabolites using the Mann\u2013Whitney\n                    <jats:italic>U<\/jats:italic>\n                    \u2010test revealed that six lipid metabolites were significantly increased in COVID\u201019 patients, including the lipid mediators arachidonic acid (AA) and eicosapentaenoic acid (EPA), which both give rise to eicosanoids. Key lipids implicated in inflammation, including AA and EPA, along with the fatty acids DHA and DPA, were significantly and positively correlated to the WHO disease severity score. Analysis of our bulk RNA\u2010seq dataset demonstrated distinct transcriptional profiles leading to a segregation of COVID\u201019 patients based on the WHO score. Ontology, KEGG, and Reactome analysis identified several key pathways and nodes that were enriched for genes related to innate immunity, interactions between lymphoid and nonlymphoid cells, interleukin signaling, and subsequent DNA damage pathways. EPA levels correlated with heightened cell cycling and DNA damage pathways observed in patients with a high WHO score. We studied gene expression in nasopharyngeal swabs from 58 healthy and COVID\u201019 participants and identified that genes implicated in eicosanoid synthesis, such as alox5, alox12, and alox15B, were specifically up\u2010regulated in high WHO score patients in several cell types of the nasopharynx, especially goblet cells across different viral variants (Deta and Omicron). Using published nasal scRNA\u2010seq datasets from COVID\u201019 patients, we evaluated the expression of genes implicated in eicosanoid synthesis, such as\n                    <jats:italic>ALOX5<\/jats:italic>\n                    ,\n                    <jats:italic>ALOX15,<\/jats:italic>\n                    and\n                    <jats:italic>ALOX15B<\/jats:italic>\n                    , across nasal cell types and COVID\u201019 severity groups. Altogether, our study highlights the fact that the increase in specific lipids implicated in inflammation and the genes required for their synthesis correlated with the severity of the SARS\u2010CoV\u20102 infection.\n                  <\/jats:p>","DOI":"10.1096\/fj.202403195r","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T07:15:02Z","timestamp":1746429302000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Enhanced Production of Lipid Mediators in Plasma and Activation of\n                    <scp>DNA<\/scp>\n                    Damage Pathways in\n                    <scp>PBMCs<\/scp>\n                    Are Correlated With the Severity of Ancestral\n                    <scp>SARS<\/scp>\n                    \u2010\n                    <scp>CoV<\/scp>\n                    \u20102 Infection"],"prefix":"10.1096","volume":"39","author":[{"given":"Jeffrey A.","family":"Tomalka","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Owings","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Mississippi Medical Center  Jackson Mississippi USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Galeas\u2010Pena","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Gastroenterology and Hepatology Tulane University School of Medicine  New Orleans Louisiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carly G. K.","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Program in Health Sciences &amp; Technology Harvard Medical School &amp; MIT  Boston Massachusetts USA"},{"name":"Ragon Institute of MGH, MIT, and Harvard  Cambridge Massachusetts USA"},{"name":"Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"},{"name":"Harvard Graduate Program in Biophysics Harvard University  Cambridge Massachusetts USA"},{"name":"Institute for Medical Engineering &amp; Science Massachusetts Institute of Technology  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanya O.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Mississippi Medical Center  Jackson Mississippi USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas G.","family":"Wichman","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Mississippi Medical Center  Jackson Mississippi USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Laird","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Mississippi Medical Center  Jackson Mississippi USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haley B.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Mississippi Medical Center  Jackson Mississippi USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neha S.","family":"Ghaliwal","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Mississippi Medical Center  Jackson Mississippi USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Everman","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Mississippi Medical Center  Jackson Mississippi USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yousaf","family":"Zafar","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Mississippi Medical Center  Jackson Mississippi USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaclyn M. L.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"},{"name":"Department of Immunology Harvard Medical School  Boston Massachusetts USA"},{"name":"Division of Gastroenterology, Hepatology, and Nutrition Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex K.","family":"Shalek","sequence":"additional","affiliation":[{"name":"Program in Health Sciences &amp; Technology Harvard Medical School &amp; MIT  Boston Massachusetts USA"},{"name":"Ragon Institute of MGH, MIT, and Harvard  Cambridge Massachusetts USA"},{"name":"Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"},{"name":"Harvard Graduate Program in Biophysics Harvard University  Cambridge Massachusetts USA"},{"name":"Institute for Medical Engineering &amp; Science Massachusetts Institute of Technology  Cambridge Massachusetts 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