In COVID-19, the considerable generation of ROS, due to cytokine activation, induces the irreversible non-enzymatic oxidation of 5, 6, 7, 8-tetrahydrobiopterin (BH4), a cofactor of phenylalanine 4-hydroxylase (PAH), the enzyme catalyzing the conversion of phenylalanine to tyrosine. The gene discussed is PAH; the disease is COVID-19.