Rationale for Use of Sphingosine-1-Phosphate Receptor Modulators in COVID-19 Patients: Overview of Scientific...

Area of Science:

• Immunology
• Pharmacology

Background:

• COVID-19 can cause severe immunopathology, including cytokine release syndrome and acute respiratory distress syndrome, due to maladjusted immune responses.
• Sphingosine-1-phosphate (S1P) and its receptors (S1PR) are vital for endothelial barrier integrity and immune cell regulation.
• Existing S1PR modulators like fingolimod and siponimod are effective in managing inflammatory diseases such as multiple sclerosis.

Approach:

• This review examines the role of S1PR modulators in modulating the inflammatory response to SARS-CoV-2.
• We explore the mechanisms by which S1PR modulators, including S1P1 receptor-mediated lymphocyte sequestration and S1PR-mediated endothelial barrier enhancement, may counteract COVID-19-induced hyperinflammation.
• The potential therapeutic application of fingolimod and siponimod in critically ill COVID-19 patients is discussed, considering their established efficacy and safety profiles in other inflammatory conditions.

Key Points:

• S1PR modulators can attenuate cytokine release through pathways involving protein phosphatase 2A.
• These modulators enhance pulmonary endothelial barrier function via the c-Abl tyrosine kinase pathway.
• Fingolimod and siponimod have demonstrated success in reducing inflammatory disease activity and progression in multiple sclerosis.

Conclusions:

• S1PR modulators represent a potential therapeutic strategy for mitigating SARS-CoV-2-induced hyperinflammation.
• Targeting S1PR pathways may offer a way to manage severe COVID-19 by controlling maladjusted immune responses.
• Further investigation into the use of fingolimod and siponimod in COVID-19 patients is warranted to understand their clinical utility and optimize treatment strategies.