Maladjusted immune responses to the
coronavirus disease 2019 (COVID-19), for example,
cytokine release syndrome, may result in immunopathology and
acute respiratory distress syndrome.
Sphingosine-1-phosphate (S1P), a bioactive
lipid mediator, and its
S1P receptor (S1PR) are crucial in maintaining endothelial cell chemotaxis and barrier integrity. Apart from the
S1P1 receptor-mediated mechanisms of sequestration of cytotoxic lymphocytes, including Th-17 and S1P1/2/3-mediated endothelial barrier functions, S1PR modulators may also attenuate
cytokine release via activation of
serine/
threonine protein phosphatase 2A and enhance the pulmonary endothelial barrier via the c-Abl
tyrosine kinase pathway. Chronic treatment with
fingolimod (S1PR1,3,4,5 modulator) and
siponimod (S1PR1,5 modulator) has demonstrated efficacy in reducing inflammatory disease activity and slowing down
disease progression in
multiple sclerosis. The decision to selectively suppress the immunity of a
critically ill patient with
COVID-19 remains a difficult choice. It has been suggested that treatment with
fingolimod or
siponimod may be appropriate to attenuate
severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced hyperinflammation in patients with
COVID-19 since these patients are already monitored in an
intensive care setting. Here, we review the use of S1PR modulators,
fingolimod and
siponimod, in regulating the inflammatory response to SARS-CoV-2 with the aim of understanding their potential rationale use in patients with
COVID-19.