Severity of COVID-19 Patients Predicted by Serum Sphingolipids Signature

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.