The aim of this review is to synthesize: (a) the literature showing that acute and chronic hyperglycemia are both linked to a poor prognosis in COVID-19; (b) the putative molecular mechanisms linking hyperglycemia and insulin resistance to an increased SARS-CoV-2 pathogenicity; (c) the possible modifying effect of hyperglycemia on COVID-19 therapies; and (d) the effect of glycemic control on the efficacy of vaccination against SARS-CoV-2. The gene discussed is INS; the disease is Hyperglycemia.