The intersection between periodontitis, T2DM, and COVID-19 disease occurs when, during diabetes mellitus, there is an increase in blood glucose levels (hyperglycemia) and, together with the viral infection, an exacerbated inflammatory response is triggered, increasing the production of TNF-α, IL-1β, IL-6, endocan, and NLRP3 inflammasome, and causing an increase in the PMN population, amplifying their effects and leading to a more severe course of comorbidity between these three pathologies [66,90,101]. The gene discussed is ESM1; the disease is Hyperglycemia.