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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)\u2013induced 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.<\/jats:p>","DOI":"10.1089\/jir.2022.0078","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T11:03:00Z","timestamp":1669892580000},"page":"246-256","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Rationale for Use of Sphingosine-1-Phosphate Receptor Modulators in COVID-19 Patients: Overview of Scientific Evidence"],"prefix":"10.1177","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2229-1545","authenticated-orcid":false,"given":"Thomas","family":"Hach","sequence":"first","affiliation":[{"name":"Patient Engagement, Novartis Pharma AG, Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasra","family":"Shakeri-Nejad","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology; Novartis Institutes for Biomedical Research, Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Bigaud","sequence":"additional","affiliation":[{"name":"Department of Autoimmunity, Transplantation &amp; Inflammation; Novartis Institutes for Biomedical Research, Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Dahlke","sequence":"additional","affiliation":[{"name":"Patient Engagement, Novartis Pharma AG, Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"de Micco","sequence":"additional","affiliation":[{"name":"Novartis Farma S.p.A., Origgio, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Petricoul","sequence":"additional","affiliation":[{"name":"Department of Neuroscience; Novartis Institutes for Biomedical Research, Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Graham","sequence":"additional","affiliation":[{"name":"Patient Engagement, Novartis Pharma AG, Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Piani-Meier","sequence":"additional","affiliation":[{"name":"Patient Engagement, Novartis Pharma AG, Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Turrini","sequence":"additional","affiliation":[{"name":"Department of Autoimmunity, Transplantation &amp; Inflammation; Novartis Institutes for Biomedical Research, Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Brinkmann","sequence":"additional","affiliation":[{"name":"Independent Consultant, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinando","family":"Nicoletti","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, University Sapienza of Rome, Rome, Italy."},{"name":"Department of Molecular Neuropharmacology, IRCCS Neuromed, Pozzilli, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,6,13]]},"reference":[{"key":"e_1_3_4_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000753"},{"key":"e_1_3_4_3_1","doi-asserted-by":"publisher","DOI":"10.3949\/ccjm.87a.20047"},{"key":"e_1_3_4_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168252"},{"key":"e_1_3_4_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700129"},{"key":"e_1_3_4_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2007.04.006"},{"key":"e_1_3_4_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00451.x"},{"key":"e_1_3_4_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2005.12.004"},{"key":"e_1_3_4_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3248"},{"key":"e_1_3_4_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70049-3"},{"key":"e_1_3_4_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemphyslip.2015.10.004"},{"key":"e_1_3_4_12_1","unstructured":"CDC (Centers for Disease Control and Prevention). 2021. 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