Plasma Sphingomyelin Disturbances: Unveiling Its Dual Role as a Crucial Immunopathological Factor and a Severity Prognostic Biomarker in COVID-19.

Autor: Toro DM; Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeirão Preto-FCFRP, University of Sao Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil.; Postgraduate Program in Basic and Applied Immunology-PPGIBA, Institute of Biological Sciences, Federal University of Amazonas-UFAM, Manaus 69080-900, AM, Brazil., da Silva-Neto PV; Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeirão Preto-FCFRP, University of Sao Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil.; Postgraduate Program in Basic and Applied Immunology-PPGIBA, Institute of Biological Sciences, Federal University of Amazonas-UFAM, Manaus 69080-900, AM, Brazil., de Carvalho JCS; Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeirão Preto-FCFRP, University of Sao Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil.; Department of Chemistry, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto-FFCLRP, University of São Paulo-USP, Ribeirão Preto 14040-901, SP, Brazil., Fuzo CA; Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeirão Preto-FCFRP, University of Sao Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil., Pérez MM; Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeirão Preto-FCFRP, University of Sao Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil., Pimentel VE; Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeirão Preto-FCFRP, University of Sao Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil.; Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirão Preto-FMRP, University of São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil., Fraga-Silva TFC; Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirão Preto-FMRP, University of São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil., Oliveira CNS; Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeirão Preto-FCFRP, University of Sao Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil.; Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirão Preto-FMRP, University of São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil., Caruso GR; Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeirão Preto-FCFRP, University of Sao Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil., Vilela AFL; Department of Chemistry, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto-FFCLRP, University of São Paulo-USP, Ribeirão Preto 14040-901, SP, Brazil., Nobre-Azevedo P; Department of Chemistry, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto-FFCLRP, University of São Paulo-USP, Ribeirão Preto 14040-901, SP, Brazil.; Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirão Preto-FMRP, University of São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil., Defelippo-Felippe TV; Department of Chemistry, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto-FFCLRP, University of São Paulo-USP, Ribeirão Preto 14040-901, SP, Brazil., Argolo JGM; Department of General and Specialized Nursing, School of Nursing of Ribeirão Preto-EERP, University of São Paulo-USP, Ribeirão Preto 14040-902, SP, Brazil., Degiovani AM; Hospital Santa Casa de Misericórdia de Ribeirão Preto, Ribeirão Preto 14085-000, SP, Brazil., Ostini FM; Hospital Santa Casa de Misericórdia de Ribeirão Preto, Ribeirão Preto 14085-000, SP, Brazil., Feitosa MR; Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto-FMRP, University of São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil.; Hospital São Paulo, Ribeirão Preto 14025-100, SP, Brazil., Parra RS; Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto-FMRP, University of São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil.; Hospital São Paulo, Ribeirão Preto 14025-100, SP, Brazil., Vilar FC; Hospital São Paulo, Ribeirão Preto 14025-100, SP, Brazil.; Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto-FMRP, University of São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil., Gaspar GG; Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto-FMRP, University of São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil., Rocha JJRD; Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto-FMRP, University of São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil., Feres O; Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto-FMRP, University of São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil.; Hospital São Paulo, Ribeirão Preto 14025-100, SP, Brazil., Costa GP; School of Physical Education and Sport of Ribeirão Preto, University of São Paulo-USP, Ribeirão Preto 14040-900, SP, Brazil., Maruyama SRC; Department of Genetics and Evolution, Center for Biological and Health Sciences, Federal University of São Carlos (UFSCar), São Carlos 13565-905, SP, Brazil., Russo EMS; Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeirão Preto-FCFRP, University of Sao Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil., Fernandes APM; Department of General and Specialized Nursing, School of Nursing of Ribeirão Preto-EERP, University of São Paulo-USP, Ribeirão Preto 14040-902, SP, Brazil., Santos IKFM; Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirão Preto-FMRP, University of São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil., Malheiro A; Postgraduate Program in Basic and Applied Immunology-PPGIBA, Institute of Biological Sciences, Federal University of Amazonas-UFAM, Manaus 69080-900, AM, Brazil., Sadikot RT; Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA., Bonato VLD; Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirão Preto-FMRP, University of São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil., Cardoso CRB; Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeirão Preto-FCFRP, University of Sao Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil., Dias-Baruffi M; Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeirão Preto-FCFRP, University of Sao Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil., Trapé ÁA; School of Physical Education and Sport of Ribeirão Preto, University of São Paulo-USP, Ribeirão Preto 14040-900, SP, Brazil., Faccioli LH; Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of Ribeirão Preto-FCFRP, University of Sao Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil., Sorgi CA; Postgraduate Program in Basic and Applied Immunology-PPGIBA, Institute of Biological Sciences, Federal University of Amazonas-UFAM, Manaus 69080-900, AM, Brazil.; Department of Chemistry, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto-FFCLRP, University of São Paulo-USP, Ribeirão Preto 14040-901, SP, Brazil.; Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirão Preto-FMRP, University of São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil., ImmunoCovid Consortium Group
Jazyk: angličtina
Zdroj: Cells [Cells] 2023 Jul 26; Vol. 12 (15). Date of Electronic Publication: 2023 Jul 26.
DOI: 10.3390/cells12151938
Abstrakt: 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 "lipid storm", 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.
Databáze: MEDLINE
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