Because no loci in ChrX has been genetically associated with severe COVID-19 [21,22,23,24], we interpret that SARS-CoV2 binding and inducing ACE2 degradation may indirectly cause gender difference involving both renal endocrine and immune responses through the renin-angiotensin-aldosterone system (RAAS) axis [62,63,64]. The gene discussed is REN; the disease is COVID-19.