In order to investigate the involvement of arginine metabolic pathways in COVID-19-associated endothelial damage, we first evaluated the immune-mediated effects of Spike S1 protein of SARS-CoV-2 on the expression of both nitric oxide synthase (NOS3/eNOS) and ARG2/arginase enzymes in endothelial cells in vitro. Here, NOS3 is linked to COVID-19.