Mechanistically, it has been proposed that hyperglycemia might be a disease-modifier for COVID-19 through multiple mechanisms: (a) induction of glycation and oligomerization of ACE2, the main receptor of SARS-CoV-2; (b) increased expression of the serine protease TMPRSS2, responsible for S protein priming; (c) impairment of the function of innate and adaptive immunity despite the induction of higher pro-inflammatory responses, both local and systemic. This evidence concerns the gene TMPRSS2 and Hyperglycemia.