Decreased serum level of sphingosine‐1‐phosphate: a novel predictor of clinical severity in COVID‐19

Abstract

The severity of coronavirus disease 2019 (COVID‐19) is a crucial problem in patient treatment and outcome. The aim of this study is to evaluate circulating level of sphingosine‐1‐phosphate (S1P) along with severity markers, in COVID‐19 patients. One hundred eleven COVID‐19 patients and forty‐seven healthy subjects were included. The severity of COVID‐19 was found significantly associated with anemia, lymphocytopenia, and significant increase of neutrophil‐to‐lymphocyte ratio, ferritin, fibrinogen, aminotransferases, lactate dehydrogenase (LDH), C‐reactive protein (CRP), and D‐dimer. Serum S1P level was inversely associated with COVID‐19 severity, being significantly correlated with CRP, LDH, ferritin, and D‐dimer. The decrease in S1P was strongly associated with the number of erythrocytes, the major source of plasma S1P, and both apolipoprotein M and albumin, the major transporters of blood S1P. Not last, S1P was found to be a relevant predictor of admission to an intensive care unit, and patient’s outcome. Circulating S1P emerged as negative biomarker of severity/mortality of COVID‐19 patients. Restoring abnormal S1P levels to a normal range may have the potential to be a therapeutic target in patients with COVID‐19.

Impact of SARS-CoV-2 infection on the recovery of peripheral blood mononuclear cells by density gradient

“…The contribution of cell-mediated immunity, both innate and acquired, is yet unclear, though lymphopenia appears to be one of the main features of this viral disease 37 , 38 and also the presence of an atypical monocyte population 39 . It has been also reported that increased levels of neutrophil‐to‐lymphocyte ratio (NLR) reflecting an enhanced systemic inflammation may predict the clinical severity and suggest a poor prognosis 40 , 41 .…”

Sphingolipidomics in Translational Sepsis Research–Biomedical Considerations and Perspectives

“…Furthermore, S1P was exhibiting strong predictive value for admission to ICU and patient outcome, for morbidity and severity of the clinical course. As a consequence, restoration to normal S1P-values was supposed as a therapeutic strategy in patients with COVID-19 (96).…”

The riddle of the Sphinx: why sphingosine‐1‐phosphate may help define molecular mechanisms underlying risk stratification for serious COVID‐19 infections

“…The article in this issue of EMBO Molecular Medicine by Marfia and colleagues (Marfia et al , 2021) asks such a simple and impertinent question. They suggest a potential mechanistic linkage between a serum measurement of sphingosine‐1‐phosphate (S1P) and the progression to and outcome of the serious inflammatory phase of COVID‐19 infection.…”

“…In contrast, S1P1 receptor antagonists exacerbated cytokine storm and lethality (Teijaro et al , 2016). The role of S1P signaling tone is tantalizingly framed in the Marfia et al (2021) study.…”

“…ApoM levels can be considered a surrogate for the plasma S1P reservoir, that delivers S1P to its receptors, and indeed, Marfia et al (2021) show a significant Pearson correlation between S1P and ApoM levels, even though HDL‐C levels were not available for all COVID‐19 patients. HDL‐C had a mean of 59 mg/dl in healthy controls and a range from 47 to 72 mg/dl which contrasted with 36 (28–45) mg/dl for patients admitted with COVID‐19 ( P < 0.0001).…”