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

Rosen, Hugh; Oldstone, Michael B. A.

doi:10.15252/emmm.202013533

Cited by 9 publications

(10 citation statements)

References 6 publications

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“…S1P, which is a signaling molecule, exerts multiple functions, including regulating the cytokine storm through its specific G protein-coupled receptors. S1P was significantly reduced in the peripheral blood of patients with COVID-19, and lower S1P meant worse prognosis [15,22,26]. In this study, S1P was found to have the lowest level at the time of discharge and gradually increased during the recovery process.…”

Section: Key Metabolic and Microbial Biomarkers Promote The Recoverymentioning

confidence: 46%

Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up

et al. 2022

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Background Due to the outbreak and rapid spread of coronavirus disease 2019 (COVID-19), more than 160 million patients have become convalescents worldwide to date. Significant alterations have occurred in the gut and oral microbiome and metabonomics of patients with COVID-19. However, it is unknown whether their characteristics return to normal after the 1-year recovery. Methods We recruited 35 confirmed patients to provide specimens at discharge and one year later, as well as 160 healthy controls. A total of 497 samples were prospectively collected, including 219 tongue-coating, 129 stool and 149 plasma samples. Tongue-coating and stool samples were subjected to 16S rRNA sequencing, and plasma samples were subjected to untargeted metabolomics testing. Results The oral and gut microbiome and metabolomics characteristics of the 1-year convalescents were restored to a large extent but did not completely return to normal. In the recovery process, the microbial diversity gradually increased. Butyric acid-producing microbes and Bifidobacterium gradually increased, whereas lipopolysaccharide-producing microbes gradually decreased. In addition, sphingosine-1-phosphate, which is closely related to the inflammatory factor storm of COVID-19, increased significantly during the recovery process. Moreover, the predictive models established based on the microbiome and metabolites of patients at the time of discharge reached high efficacy in predicting their neutralizing antibody levels one year later. Conclusions This study is the first to characterize the oral and gut microbiome and metabonomics in 1-year convalescents of COVID-19. The key microbiome and metabolites in the process of recovery were identified, and provided new treatment ideas for accelerating recovery. And the predictive models based on the microbiome and metabolomics afford new insights for predicting the recovery situation which benefited affected individuals and healthcare.

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Section: Key Metabolic and Microbial Biomarkers Promote The Recoverymentioning

confidence: 46%

Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up

et al. 2022

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“…Recent studies indicate that levels of S1P in patient serum change during the course of COVID-19 with lower circulating S1P observed in patients with a more severe clinical course (Marfia et al, 2021;Rosen and Oldstone, 2021). In view of this, it was suggested that S1P could be a prognostic marker to define the outcome of COVID-19.…”

Section: S1p As a Prognostic Marker For Sars-cov-2mentioning

confidence: 99%

Sphingolipids as Modulators of SARS-CoV-2 Infection

Törnquist

Asghar

Srinivasan

et al. 2021

Front. Cell Dev. Biol.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic with severe consequences for afflicted individuals and the society as a whole. The biology and infectivity of the virus has been intensively studied in order to gain a better understanding of the molecular basis of virus-host cell interactions during infection. It is known that SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) via its spike protein. Priming of the virus by specific proteases leads to viral entry via endocytosis and to the subsequent steps in the life cycle of SARS-CoV-2. Sphingosine and ceramide belong to the sphingolipid family and are abundantly present in cell membranes. These lipids were recently shown to interfere with the uptake of virus particles of SARS-CoV-2 into epithelial cell lines and primary human nasal cells in culture. The mechanisms of action were partly different, as sphingosine blocked, whilst ceramide facilitated viral entry. Acid sphingomyelinase (ASM) is vital for the generation of ceramide and functional inhibition of ASM by drugs like amitriptyline reduced SARS-CoV-2 entry into the epithelial cells. Recent data indicates that serum level of sphingosine-1-phosphate (S1P) is a prognostic factor for COVID-2 severity. Further, stimulation of sphingosine-1-phosphate receptor 1 (S1PR1) might also constrain the hyper-inflammatory conditions linked to SARS-CoV-2. Here, we review recent exciting findings regarding sphingolipids in the uptake of SARS-CoV-2 and in the course of COVID-19 disease. More studies are required on the mechanisms of action and the potential use of antidepressant drugs and sphingolipid modifiers in SARS-CoV-2 infections and in the treatment of the more serious and fatal consequences of the disease.

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“… 212 S1P/S1PR pathway is also closely associated with neuroinflammation, vascular disease, and other complications of COVID‐19. 213 , 214 S1P can act as an intracellular second messenger and receptor ligand, and regulation of innate and adaptive immunity is mediated primarily through binding to specific GTP‐binding protein‐coupled receptors (S1PR1‐5). 209 , 215 These S1PRs determine multiple responses and are discrepantly expressed in different tissues.…”

Section: Inflammatory Pathways In Covid‐19mentioning

confidence: 99%

“…S1P was considered as a new predictor of clinical severity associated with COVID‐19 212 . S1P/S1PR pathway is also closely associated with neuroinflammation, vascular disease, and other complications of COVID‐19 213,214 . S1P can act as an intracellular second messenger and receptor ligand, and regulation of innate and adaptive immunity is mediated primarily through binding to specific GTP‐binding protein‐coupled receptors (S1PR1‐5) 209,215 .…”

Section: Inflammatory Pathways In Covid‐19mentioning

confidence: 99%

Inflammatory pathways in COVID‐19: Mechanism and therapeutic interventions

Jiang

Zhao

Zhou

et al. 2022

MedComm

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The 2019 coronavirus disease (COVID‐19) pandemic has become a global crisis. In the immunopathogenesis of COVID‐19, SARS‐CoV‐2 infection induces an excessive inflammatory response in patients, causing an inflammatory cytokine storm in severe cases. Cytokine storm leads to acute respiratory distress syndrome, pulmonary and other multiorgan failure, which is an important cause of COVID‐19 progression and even death. Among them, activation of inflammatory pathways is a major factor in generating cytokine storms and causing dysregulated immune responses, which is closely related to the severity of viral infection. Therefore, elucidation of the inflammatory signaling pathway of SARS‐CoV‐2 is important in providing otential therapeutic targets and treatment strategies against COVID‐19. Here, we discuss the major inflammatory pathways in the pathogenesis of COVID‐19, including induction, function, and downstream signaling, as well as existing and potential interventions targeting these cytokines or related signaling pathways. We believe that a comprehensive understanding of the regulatory pathways of COVID‐19 immune dysregulation and inflammation will help develop better clinical therapy strategies to effectively control inflammatory diseases, such as COVID‐19.

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

Cited by 9 publications

References 6 publications

Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up

Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up

Sphingolipids as Modulators of SARS-CoV-2 Infection

Inflammatory pathways in COVID‐19: Mechanism and therapeutic interventions

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