ACE2 and COVID-19: Moreover, a single-nucleotide polymorphism (SNP) within the androgen response element in an enhancer located 13 kb upstream of TMPRSS2 transcription start site reduces binding and transactivation by the androgen receptor (37)—a signaling pathway that also modulates both TMPRSS2 and ACE2 expression and is associated with severe COVID-19 symptoms in men (38, 39).