Combating viral disease outbreaks has doubtlessly been one of the major public health challenges for the 21^st century. Here, the host entry machinery required for COVID-19 (SARS-CoV-2) infection was examined for the gene expression profiles and polymorphism. The four human population groups of Europeans, Africans, Asians, and Americans had specific and also a shared pool of variants for the X-linked locus of ACE2 receptor. Several specific and common ACE2 variants were of the utmost importance to the viral entry and infection. In the absence of gender bias for the gene expression profiles, the hemizygous rare variants of ACE2 describe the observed higher mortality rate in males. Finally, a personalized medicine strategy is conceived for isolating high-risk individuals in epidemic circumstances.