Phospholipid-dependent mechanisms regulating TF procoagulant activity. (A) Resting cells have an asymmetric phospholipid distribution. PS is located in the inner leaflet of the membrane but translocates upon cell activation. In turn, FX binds to the membrane and is activated by the TF and FVIIa complex to FXa. (B) Upon infection with SARS-CoV-2-SP-PV, ASMase translocates from lysosomes to the plasma membrane. SM, the substrate of ASMase, is present in the outer leaflet and is hydrolyzed by SM into ceramide and phosphorylcholine, thereby triggering the TF procoagulant activity and activating FX to FXa. Professional illustration by Patrick Lane, ScEYEnce Studios.