The reason behind the high inter-individual variability in response to SARS-CoV-2 infection and patient’s outcome is poorly understood. The present study targets the sphingolipid profile of twenty-four healthy controls and fifty-nine COVID-19 patients with different disease severity. Sera were analyzed by untargeted and targeted mass spectrometry and ELISA. Results indicated a progressive increase in dihydrosphingosine, dihydroceramides, ceramides, sphingosine, and a decrease in sphingosine-1-phosphate. These changes are associated with a serine palmitoyltransferase long chain base subunit 1 (SPTLC1) increase in relation to COVID-19 severity. Severe patients showed a decrease in sphingomyelins and a high level of acid sphingomyelinase (aSMase) that influences monosialodihexosyl ganglioside (GM3) C16:0 levels. Critical patients are characterized by high levels of dihydrosphingosine and dihydroceramide but not of glycosphingolipids. In severe and critical patients, unbalanced lipid metabolism induces lipid raft remodeling, leads to cell apoptosis and immunoescape, suggesting active sphingolipid participation in viral infection. Furthermore, results indicated that the sphingolipid and glycosphingolipid metabolic rewiring promoted by aSMase and GM3 is age-dependent but also characteristic of severe and critical patients influencing prognosis and increasing viral load. AUCs calculated from ROC curves indicated ceramides C16:0, C18:0, C24:1, sphingosine and SPTLC1 as putative biomarkers of disease evolution.

Severity of COVID-19 Patients Predicted by Serum Sphingolipids Signature / E. Torretta, M. Garziano, M. Poliseno, D. Capitanio, M. Biasin, T. Antonia Santantonio, M.S. Clerici, S. Lo Caputo, D.L. Trabattoni, C. Gelfi. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 22:19(2021 Sep 22), pp. 10198.1-10198.22. [10.3390/ijms221910198]

Severity of COVID-19 Patients Predicted by Serum Sphingolipids Signature

E. Torretta
Primo
;
M. Garziano
Secondo
;
D. Capitanio;M. Biasin;M.S. Clerici;D.L. Trabattoni
Penultimo
;
C. Gelfi
Ultimo
2021

Abstract

The reason behind the high inter-individual variability in response to SARS-CoV-2 infection and patient’s outcome is poorly understood. The present study targets the sphingolipid profile of twenty-four healthy controls and fifty-nine COVID-19 patients with different disease severity. Sera were analyzed by untargeted and targeted mass spectrometry and ELISA. Results indicated a progressive increase in dihydrosphingosine, dihydroceramides, ceramides, sphingosine, and a decrease in sphingosine-1-phosphate. These changes are associated with a serine palmitoyltransferase long chain base subunit 1 (SPTLC1) increase in relation to COVID-19 severity. Severe patients showed a decrease in sphingomyelins and a high level of acid sphingomyelinase (aSMase) that influences monosialodihexosyl ganglioside (GM3) C16:0 levels. Critical patients are characterized by high levels of dihydrosphingosine and dihydroceramide but not of glycosphingolipids. In severe and critical patients, unbalanced lipid metabolism induces lipid raft remodeling, leads to cell apoptosis and immunoescape, suggesting active sphingolipid participation in viral infection. Furthermore, results indicated that the sphingolipid and glycosphingolipid metabolic rewiring promoted by aSMase and GM3 is age-dependent but also characteristic of severe and critical patients influencing prognosis and increasing viral load. AUCs calculated from ROC curves indicated ceramides C16:0, C18:0, C24:1, sphingosine and SPTLC1 as putative biomarkers of disease evolution.
COVID-19; COVID-19 severity; sphingolipids; acid sphingomyelinase; serine palmitoyltransferase; caspase 3; frailty; mass spectrometry;
Settore BIO/13 - Biologia Applicata
Settore MED/04 - Patologia Generale
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
CAR_EXT20CGELF_01 - S1P levels and quali/quantitative sphingolipid profile to identify early predictive markers to target hypoxia adaptation and inflammatory response in plasma of COV19-SARS-2 patients to prevent the negative outcome toward severe pulmonary insufficiency. - TRABATTONI, DARIA LUCIA - CAR_EXT - CARIPLO - EXTRABANDO E PROGETTI TERRITORIALI - 2020
22-set-2021
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/870510
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