THE DANGER OF HYPERGLYCEMIA DURING COVID-19

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) is an RNA beta-coronavirus responsible for the coronavirus disease 2019 (COVID-19). COVID-19 encompasses a large range of disease severity, from mild symptoms to severe forms with Intensive Care Unit admission and eventually death. The severe forms of COVID-19 are usually observed in high-risk patients, as those with type two diabetes mellitus. Acute hyperglycemia at hospital admission represents a risk factor for poor COVID-19 prognosis in patients with and without diabetes. Acute and chronic glycemic control are both emerging as major determinants of vaccination efficacy, disease severity, and mortality rate in COVID-19 patients. Mechanistically, it has been proposed that hyperglycemia might be a disease-modifier for COVID-19 through multiple mechanisms 1- induction of glycation and oligomerization of ACE2, the main receptor of SARS-CoV-2;2- increased expression of the serine protease TMPRSS2, responsible for S protein priming;3- impairment of the function of innate and adaptive immunity despite the induction of higher pro-inflammatory responses, both local and systemic. Consistently, managing acute hyperglycemia through insulin infusion has been suggested to improve clinical outcomes while implementing chronic glycemic control positively affects the immune response following vaccination. Here, we review the available evidence linking acute and chronic hyperglycemia to COVID-19 outcomes, describing also the putative mediators of such interactions and proposing glycemic control as a potential route to optimize disease prevention and management.