This review provides a comprehensive overview of SARS-CoV-2 infection, the resultant severe symptoms caused by the virus, our current strategies for treatment, and importantly, discusses how we can we use our knowledge of the SphK/ S1P/S1PR pathway to design therapeutic strategies to provide some relief from, and to combat, the severe, unprecedented symptoms of COVID-19 and the chronic health problems emerging in an increasing number of patients. This evidence concerns the gene MBTPS1 and COVID-19.