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One of the disease hallmarks is hyper\u2010inflammatory responses, which usually leads to a severe lung disease. Patients with COVID\u201019 also frequently suffer from neurological symptoms such as acute diffuse encephalomyelitis, brain injury and psychiatric complications. The metabolic pathway of sphingosine\u20101\u2010phosphate (S1P) is a dynamic regulator of various cell types and disease processes, including the nervous system. It has been demonstrated that S1P and its metabolic enzymes, regulating neuroinflammation and neurogenesis, exhibit important functions during viral infection. S1P receptor 1 (S1PR1) analogues including AAL\u2010R and RP\u2010002 inhibit pathophysiological responses at the early stage of H1N1 virus infection and then play a protective role. Fingolimod (FTY720) is an S1P receptor modulator and is being tested for treating COVID\u201019. Our review provides an overview of SARS\u2010CoV\u20102 infection and critical role of the SphK\u2010S1P\u2010SIPR pathway in invasion of SARS\u2010CoV\u20102 infection, particularly in the central nervous system (CNS). This may help design therapeutic strategies based on the S1P\u2010mediated signal transduction, and the adjuvant therapeutic effects of S1P analogues to limit or prevent the interaction between the host and SARS\u2010CoV\u20102, block the spread of the SARS\u2010CoV\u20102, and consequently treat related complications in the CNS.<\/jats:p>","DOI":"10.1111\/1440-1681.13483","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T03:58:05Z","timestamp":1612929485000},"page":"637-650","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Role of the SphK\u2010S1P\u2010S1PRs pathway in invasion of the nervous system by SARS\u2010CoV\u20102 infection"],"prefix":"10.1111","volume":"48","author":[{"given":"Yuehai","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Hand and Foot Surgery The Affiliated Hospital of Qingdao University Shangdong 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