{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:40:10Z","timestamp":1786538410111,"version":"build-2736575974"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T00:00:00Z","timestamp":1696377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The SARS-CoV-2 mediated COVID-19 pandemic has impacted millions worldwide. Hyper-inflammatory processes, including cytokine storm, contribute to long-standing tissue injury and damage in COVID-19. The metabolism of sphingolipids as regulators of cell survival, differentiation, and proliferation has been implicated in inflammatory signaling and cytokine responses. Sphingosine-kinase-1 (SK1) and ceramide-synthase-2 (CERS2) generate metabolites that regulate the anti- and pro-apoptotic processes, respectively. Alterations in SK1 and CERS2 expression may contribute to the inflammation and tissue damage during COVID-19. The central objective of this study is to evaluate structural changes in the lung post-SARS-CoV-2 infection and to investigate whether the sphingolipid rheostat is altered in response to SARS-CoV-2 infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Central and peripheral lung tissues from COVID-19+ or control autopsies and resected lung tissue from COVID-19 convalescents were subjected to histologic evaluation of airspace and collagen deposisiton, and immunohistochemical evaluation of SK1 and CERS2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we report significant reduction in air space and increase in collagen deposition in lung autopsy tissues from patients who died from COVID-19 (COVID-19<jats:sup>+<\/jats:sup>) and COVID-19 convalescent individuals. SK1 expression increased in the lungs of COVID-19<jats:sup>+<\/jats:sup> autopsies and COVID-19 convalescent lung tissue compared to controls and was mostly associated with Type II pneumocytes and alveolar macrophages. No significant difference in CERS2 expression was noted. SARS-CoV-2 infection upregulates SK1 and increases the ratio of SK1 to CERS2 expression in lung tissues of COVID-19 autopsies and COVID-19 convalescents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These data suggest an alteration in the sphingolipid rheostat in lung tissue during COVID-19, suggesting a potential contribution to the inflammation and tissue damage associated with viral infection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1216278","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T13:42:19Z","timestamp":1696513339000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Altered sphingolipid pathway in SARS-CoV-2 infected human lung tissue"],"prefix":"10.3389","volume":"14","author":[{"given":"Rabisa J.","family":"Khan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sierra 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