Plasma Sphingomyelin Disturbances: Unveiling Its Dual Role as a Crucial Immunopathological Factor and a Severity Prognostic Biomarker in COVID-19
Diana Mota Toro,
Pedro V. da Silva-Neto,
Jonatan C. S. de Carvalho,
Carlos A. Fuzo,
Malena M. Pérez,
Vinícius E. Pimentel,
Thais F. C. Fraga-Silva,
Camilla N. S. Oliveira,
Glaucia R. Caruso,
Adriana F. L. Vilela,
Pedro Nobre-Azevedo,
Thiago V. Defelippo-Felippe,
Jamille G. M. Argolo,
Augusto M. Degiovani,
Fátima M. Ostini,
Marley R. Feitosa,
Rogerio S. Parra,
Fernando C. Vilar,
Gilberto G. Gaspar,
José J. R. da Rocha,
Omar Feres,
Gabriel P. Costa,
Sandra R. C. Maruyama,
Elisa M. S. Russo,
Ana Paula M. Fernandes,
Isabel K. F. M. Santos,
Adriana Malheiro,
Ruxana T. Sadikot,
Vânia L. D. Bonato,
Cristina R. B. Cardoso,
Marcelo Dias-Baruffi,
Átila A. Trapé,
Lúcia H. Faccioli,
Carlos A. Sorgi,
ImmunoCovid Consortium Group
Affiliations
Diana Mota Toro
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
Pedro V. da Silva-Neto
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
Jonatan C. S. de Carvalho
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
Carlos A. Fuzo
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
Malena M. Pérez
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
Vinícius E. Pimentel
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
Thais F. C. Fraga-Silva
Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirão Preto–FMRP, University of São Paulo–USP, Ribeirão Preto 14049-900, SP, Brazil
Camilla N. S. Oliveira
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
Glaucia R. Caruso
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
Adriana F. L. Vilela
Department of Chemistry, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto–FFCLRP, University of São Paulo–USP, Ribeirão Preto 14040-901, SP, Brazil
Pedro Nobre-Azevedo
Department of Chemistry, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto–FFCLRP, University of São Paulo–USP, Ribeirão Preto 14040-901, SP, Brazil
Thiago V. Defelippo-Felippe
Department of Chemistry, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto–FFCLRP, University of São Paulo–USP, Ribeirão Preto 14040-901, SP, Brazil
Jamille G. M. Argolo
Department of General and Specialized Nursing, School of Nursing of Ribeirão Preto–EERP, University of São Paulo–USP, Ribeirão Preto 14040-902, SP, Brazil
Augusto M. Degiovani
Hospital Santa Casa de Misericórdia de Ribeirão Preto, Ribeirão Preto 14085-000, SP, Brazil
Fátima M. Ostini
Hospital Santa Casa de Misericórdia de Ribeirão Preto, Ribeirão Preto 14085-000, SP, Brazil
Marley R. Feitosa
Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto-FMRP, University of São Paulo–USP, Ribeirão Preto 14049-900, SP, Brazil
Rogerio S. Parra
Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto-FMRP, University of São Paulo–USP, Ribeirão Preto 14049-900, SP, Brazil
Fernando C. Vilar
Hospital São Paulo, Ribeirão Preto 14025-100, SP, Brazil
Gilberto G. Gaspar
Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto–FMRP, University of São Paulo–USP, Ribeirão Preto 14049-900, SP, Brazil
José J. R. da Rocha
Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto-FMRP, University of São Paulo–USP, Ribeirão Preto 14049-900, SP, Brazil
Omar Feres
Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto-FMRP, University of São Paulo–USP, Ribeirão Preto 14049-900, SP, Brazil
Gabriel P. Costa
School of Physical Education and Sport of Ribeirão Preto, University of São Paulo–USP, Ribeirão Preto 14040-900, SP, Brazil
Sandra R. C. Maruyama
Department of Genetics and Evolution, Center for Biological and Health Sciences, Federal University of São Carlos (UFSCar), São Carlos 13565-905, SP, Brazil
Elisa M. S. Russo
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
Ana Paula M. Fernandes
Department of General and Specialized Nursing, School of Nursing of Ribeirão Preto–EERP, University of São Paulo–USP, Ribeirão Preto 14040-902, SP, Brazil
Isabel K. F. M. Santos
Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirão Preto–FMRP, University of São Paulo–USP, Ribeirão Preto 14049-900, SP, Brazil
Adriana Malheiro
Postgraduate Program in Basic and Applied Immunology–PPGIBA, Institute of Biological Sciences, Federal University of Amazonas–UFAM, Manaus 69080-900, AM, Brazil
Ruxana T. Sadikot
Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
Vânia L. D. Bonato
Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirão Preto–FMRP, University of São Paulo–USP, Ribeirão Preto 14049-900, SP, Brazil
Cristina R. B. Cardoso
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
Marcelo Dias-Baruffi
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
Átila A. Trapé
School of Physical Education and Sport of Ribeirão Preto, University of São Paulo–USP, Ribeirão Preto 14040-900, SP, Brazil
Lúcia H. Faccioli
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
Carlos A. Sorgi
Postgraduate Program in Basic and Applied Immunology–PPGIBA, Institute of Biological Sciences, Federal University of Amazonas–UFAM, Manaus 69080-900, AM, Brazil
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.
