On the other hand, the modulation of S1P release/content, through S1P transporter (i.e., Spns2), SphK and/or S1P lyase activities, and S1PR-mediated signaling may be important therapeutic approaches for COVID-19 because they might prevent SARS-CoV-2 infection or virus propagation (Figure 2). This evidence concerns the gene SPNS2 and COVID-19.