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(PIPAE)","award":["312606\/2019-2"],"award-info":[{"award-number":["312606\/2019-2"]}]},{"name":"Integrated Research Projects in Strategic Areas (PIPAE)","award":["313259\/2022-4"],"award-info":[{"award-number":["313259\/2022-4"]}]},{"name":"Integrated Research Projects in Strategic Areas (PIPAE)","award":["303259\/2020-5"],"award-info":[{"award-number":["303259\/2020-5"]}]},{"name":"Integrated Research Projects in Strategic Areas (PIPAE)","award":["309583\/2019-5"],"award-info":[{"award-number":["309583\/2019-5"]}]},{"name":"Integrated Research Projects in Strategic Areas (PIPAE)","award":["314358\/2021-8"],"award-info":[{"award-number":["314358\/2021-8"]}]},{"name":"Integrated Research Projects in Strategic Areas (PIPAE)","award":["3518\/2020"],"award-info":[{"award-number":["3518\/2020"]}]},{"name":"Integrated Research Projects in Strategic Areas (PIPAE)","award":["2021.1.10424.1.9"],"award-info":[{"award-number":["2021.1.10424.1.9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>SARS-CoV-2 infection triggers distinct patterns of disease development characterized by significant alterations in host regulatory responses. Severe cases exhibit profound lung inflammation and systemic repercussions. Remarkably, critically ill patients display a \u201clipid storm\u201d, influencing the inflammatory process and tissue damage. Sphingolipids (SLs) play pivotal roles in various cellular and tissue processes, including inflammation, metabolic disorders, and cancer. In this study, we employed high-resolution mass spectrometry to investigate SL metabolism in plasma samples obtained from control subjects (n = 55), COVID-19 patients (n = 204), and convalescent individuals (n = 77). These data were correlated with inflammatory parameters associated with the clinical severity of COVID-19. Additionally, we utilized RNAseq analysis to examine the gene expression of enzymes involved in the SL pathway. Our analysis revealed the presence of thirty-eight SL species from seven families in the plasma of study participants. The most profound alterations in the SL species profile were observed in patients with severe disease. Notably, a predominant sphingomyelin (SM d18:1) species emerged as a potential biomarker for COVID-19 severity, showing decreased levels in the plasma of convalescent individuals. Elevated SM levels were positively correlated with age, hospitalization duration, clinical score, and neutrophil count, as well as the production of IL-6 and IL-8. Intriguingly, we identified a putative protective effect against disease severity mediated by SM (d18:1\/24:0), while ceramide (Cer) species (d18:1\/24:1) and (d18:1\/24:0)were associated with increased risk. Moreover, we observed the enhanced expression of key enzymes involved in the SL pathway in blood cells from severe COVID-19 patients, suggesting a primary flow towards Cer generation in tandem with SM synthesis. These findings underscore the potential of SM as a prognostic biomarker for COVID-19 and highlight promising pharmacological targets. By targeting sphingolipid pathways, novel therapeutic strategies may emerge to mitigate the severity of COVID-19 and improve patient outcomes.<\/jats:p>","DOI":"10.3390\/cells12151938","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T01:50:37Z","timestamp":1690422637000},"page":"1938","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Plasma Sphingomyelin Disturbances: Unveiling Its Dual Role as a Crucial Immunopathological Factor and a Severity Prognostic Biomarker in COVID-19"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1003-3848","authenticated-orcid":false,"given":"Diana Mota","family":"Toro","sequence":"first","affiliation":[{"name":"Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeir\u00e3o Preto\u2013FCFRP, University of Sao Paulo\u2013USP, Ribeir\u00e3o Preto 14040-903, SP, Brazil"},{"name":"Postgraduate Program in Basic and Applied Immunology\u2013PPGIBA, Institute of Biological Sciences, Federal University of Amazonas\u2013UFAM, Manaus 69080-900, AM, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1209-9346","authenticated-orcid":false,"given":"Pedro V.","family":"da Silva-Neto","sequence":"additional","affiliation":[{"name":"Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeir\u00e3o Preto\u2013FCFRP, University of Sao Paulo\u2013USP, Ribeir\u00e3o Preto 14040-903, SP, Brazil"},{"name":"Postgraduate Program in Basic and Applied Immunology\u2013PPGIBA, Institute of Biological Sciences, Federal University of Amazonas\u2013UFAM, Manaus 69080-900, AM, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8776-5417","authenticated-orcid":false,"given":"Jonatan C. S.","family":"de Carvalho","sequence":"additional","affiliation":[{"name":"Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeir\u00e3o Preto\u2013FCFRP, University of Sao Paulo\u2013USP, Ribeir\u00e3o Preto 14040-903, SP, Brazil"},{"name":"Department of Chemistry, Faculty of Philosophy, Sciences and Letters of Ribeir\u00e3o Preto\u2013FFCLRP, University of S\u00e3o Paulo\u2013USP, Ribeir\u00e3o Preto 14040-901, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3198-9969","authenticated-orcid":false,"given":"Carlos A.","family":"Fuzo","sequence":"additional","affiliation":[{"name":"Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeir\u00e3o Preto\u2013FCFRP, University of Sao Paulo\u2013USP, Ribeir\u00e3o Preto 14040-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malena M.","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeir\u00e3o Preto\u2013FCFRP, University of Sao Paulo\u2013USP, Ribeir\u00e3o Preto 14040-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3411-1545","authenticated-orcid":false,"given":"Vin\u00edcius E.","family":"Pimentel","sequence":"additional","affiliation":[{"name":"Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeir\u00e3o Preto\u2013FCFRP, University of Sao Paulo\u2013USP, Ribeir\u00e3o Preto 14040-903, SP, Brazil"},{"name":"Department of Biochemistry and Immunology, Faculty of Medicine of Ribeir\u00e3o Preto\u2013FMRP, University of S\u00e3o Paulo\u2013USP, Ribeir\u00e3o Preto 14049-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2053-8938","authenticated-orcid":false,"given":"Thais F. 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