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

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...

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Published in:	Cells (Basel, Switzerland) Vol. 12; no. 15; p. 1938
Main Authors:	Toro, Diana Mota, da Silva-Neto, Pedro V, de Carvalho, Jonatan C S, Fuzo, Carlos A, Pérez, Malena M, Pimentel, Vinícius E, Fraga-Silva, Thais F C, Oliveira, Camilla N S, Caruso, Glaucia R, Vilela, Adriana F L, Nobre-Azevedo, Pedro, Defelippo-Felippe, Thiago V, Argolo, Jamille G M, Degiovani, Augusto M, Ostini, Fátima M, Feitosa, Marley R, Parra, Rogerio S, Vilar, Fernando C, Gaspar, Gilberto G, Rocha, José J R da, Feres, Omar, Costa, Gabriel P, Maruyama, Sandra R C, Russo, Elisa M S, Fernandes, Ana Paula M, Santos, Isabel K F M, Malheiro, Adriana, Sadikot, Ruxana T, Bonato, Vânia L D, Cardoso, Cristina R B, Dias-Baruffi, Marcelo, Trapé, Átila A, Faccioli, Lúcia H, Sorgi, Carlos A, ImmunoCovid Consortium Group
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 26-07-2023 MDPI
Subjects:	Asymptomatic Biological markers biomarker Biomarkers Ceramides - metabolism COVID-19 Cytokines Data collection Diabetes Disease Enzymes Ethics Gene expression Health aspects Hormone replacement therapy Hospitalization Humans Immunology Infections Inflammation Interleukin 6 Interleukin 8 Kinases Laboratories Leukocytes Leukocytes (neutrophilic) Mass spectrometry Mass spectroscopy Medical prognosis Metabolic disorders Metabolism Pandemics Plasma Prognosis SARS-CoV-2 - metabolism Scientific imaging Severe acute respiratory syndrome coronavirus 2 Sphingolipids Sphingolipids - metabolism Sphingomyelin Sphingomyelins Tumor necrosis factor-TNF Brazil United States > US COVID-19 sphingomyelin biomarker inflammation sphingolipids
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Summary:	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 ( = 55), COVID-19 patients ( = 204), and convalescent individuals ( = 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work and share senior authorship. Membership of the Group Name is provided in the Appendix A. These authors contributed equally to this work and share first authorship.
ISSN:	2073-4409 2073-4409
DOI:	10.3390/cells12151938