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These disturbances may contribute to the pathophysiology of post-COVID-19 syndrome (PCS), a multifaceted condition characterized by persistent symptoms, including neuropsychiatric symptoms. The diagnosis of PCS primarily relies on symptom-based criteria. Here, we aimed to identify biomarkers associated with PCS and disease severity. This prospective single-center cohort study investigated soluble blood biomarkers related to endothelial dysfunction and amino acid, fatty acid, carnitine, eicosanoid and resolvin metabolism in individuals post-acute SARS-CoV-2 infection with or without PCS compared with individuals without documented SARS-CoV-2 infection. Additionally, we explored the association between these biomarkers and PCS-related fatigue severity as assessed by the Multidimensional Fatigue Inventory (MFI). At a median of 37.4 weeks after SARS-CoV-2 infection, participants with prior infection showed higher levels of soluble thrombomodulin (TM) and L-lactate dehydrogenase (LDH) than those without previous infection. Alterations in arginine biosynthesis and taurine and hypotaurine metabolism indicate disruption of the NO-metabolism. These findings were made in participants without and with symptoms of PCS. In participants with PCS-related high fatigue severity, concentrations of the polyunsaturated fatty acid (PUFA) linoleic acid (LA), and the monounsaturated fatty acids (MUFAs) oleic acid (OA) and palmitoleic acid (PA) were higher than in participants with low fatigue severity. Alterations in markers of endothelial dysfunction and NO-metabolism are detectable at a median of 37.4 weeks after SARS-CoV-2 infection independent of PCS-related fatigue severity. Additionally, in individuals with high PCS-related fatigue severity, specific fatty acid alterations were observed.<\/jats:p>","DOI":"10.1038\/s41598-026-50965-6","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T22:20:00Z","timestamp":1778710800000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Endothelial dysfunction and metabolic biomarkers in post-COVID-19 syndrome"],"prefix":"10.1038","volume":"16","author":[{"given":"Martin","family":"Oestreich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Dittrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronny","family":"Baber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Gaudl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madlen","family":"Reinicke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Willenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Wirkner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Then Bergh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Fricke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Rockstroh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Fertey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Ulbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Lehmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milica","family":"Matijevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Zeynalova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Engel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"L\u00f6ffler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berend","family":"Isermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uta","family":"Ceglarek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Biemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"50965_CR1","doi-asserted-by":"publisher","first-page":"e102","DOI":"10.1016\/S1473-3099(21)00703-9","volume":"22","author":"JB Soriano","year":"2022","unstructured":"Soriano, J. 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