Abstract

Background/Aims: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-stranded single-stranded RNA virus, a member of the subgenus Sarbecovirus (beta-CoV lineage B) and 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, such as those with type two diabetes mellitus. Here, we review the available evidence linking acute and chronic hyperglycemia to COVID-19 outcomes, describing also the putative mediators of such interactions. Findings/Conclusions: 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: (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. Consistently, managing acute hyperglycemia through insulin infusion has been suggested to improve clinical outcomes, while implementing chronic glycemic control positively affects immune response following vaccination. Although more research is warranted to better disentangle the relationship between hyperglycemia and COVID-19, it might be worth considering glycemic control as a potential route to optimize disease prevention and management.

Highlights

  • Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has been spreading across the world since December 2019

  • Epidemiological data suggest that acute hyperglycemia occurs in about 50% of patients hospitalized for COVID-19, while the prevalence of diabetes in the same population is about 7% [17]

  • Given the common clustering of multiple risk factors in patients with diabetes, it is difficult to establish if one component among obesity, insulin resistance, and hyperglycemia, is a more relevant driver of COVID-19 severity compared with the others

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Summary

Introduction

Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has been spreading across the world since December 2019. Corona Virus Disease 2019 (COVID-19), the disorder caused by SARS-CoV-2, can present as a highly heterogenous acute condition, ranging from patients with mild respiratory symptoms to severe or critical pneumonia [1,2]. Type 2 diabetes mellitus (T2DM) has been suggested as a risk factor for poor COVID-19 prognosis [5–8]. Patients with T2DM often present a plethora of comorbidities, e.g., cardiovascular diseases, obesity, and metabolic syndrome, which it has been suggested may mediate the observed increased risk for complicated COVID-19 [5–9]. Hyperglycemia per se has been suggested to be a potential mediator of increased disease severity and of blunted immune response to COVID-19 vaccination

Aims of the Review
Literature Selection
Hyperglycemia Worsens the Prognosis of Patients with COVID-19
Hyperglycemia and COVID-19 Therapy
Vaccination against SARS-CoV-2
Findings
Conclusions
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