Hyperglycemia and Angiotensin-Converting Enzyme 2 in Pulmonary Function in the Context of SARS-CoV-2 Infection

Abstract

Since the appearance of the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 in China, diabetes mellitus (DM) and hyperglycemia in patients infected with SARS-CoV, represent independent predictors of mortality. Therefore, metabolic control has played a major role in the prognosis of these patients. In the current pandemic of coronavirus disease 19 (COVID-19), multiple studies have shown that DM is one of the main comorbidities associated with COVID-19 and higher risk of complications and death. The incidence and prevalence of COVID-19 complications and death related with hyperglycemia in patients with or without DM are high. There are many hypotheses related with worse prognosis and death related to COVID-19 and/or hyperglycemia. However, the information about the interplay between hyperglycemia and angiotensin-converting enzyme 2 (ACE2), the critical receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the context of SARS-CoV-2 infection, is almost null, but there is enough information to consider the possible participation of hyperglycemia in the glycation of this protein, unleashing a pool of reactions leading to acute respiratory distress syndrome and death in patients with COVID-19. In this document we investigated the current evidence related with ACE2 as a key element within the pathophysiological mechanism related with hyperglycemia extrapolating it to context of SARS-CoV-2 infection and its relationship with worse prognosis and death for COVID-19.

SARS-CoV-2 infects cells lining the blood-retinal barrier and induces a hyperinflammatory immune response in the retina via systemic exposure

“…COVID-19 has demonstrated worse clinical outcomes in patients with comorbidities, such as diabetes. COVID-19 has been shown to induce hyperglycemia even in non-diabetic patients, which causes ACE2 glycation [ 44 ] and results in increased infectivity of hepatocytes [ 26 ]. To validate the BRB permissivity in comorbid conditions, we acclimatized BRB cells to normal and hyperglycemic conditions prior to infection with SARS-CoV-2.…”

“…Compared with the mock control, the SARS-CoV-2 challenge enhanced the expression of all three candidate receptors, ACE2, TMPRSS2, and AXL, in these cells, as evidenced by increased fluorescence positivity for these receptors in infected groups ( Fig 4A and 4C ). COVID-19 has been shown to modulate hyperglycemia and ACE2 expression, leading to increased complications in affected individuals[ 44 ]. Here, our results show that hyperglycemia augments the expression of ACE2, TMPRSS2, and AXL receptors on BRB cells upon infection ( Fig 4B and 4C ).…”

Gene Networks of Hyperglycemia, Diabetic Complications, and Human Proteins Targeted by SARS-CoV-2: What Is the Molecular Basis for Comorbidity?

“…ACE2, a carboxypeptidase, mediates vasodilation by cleaving angiotensin II and takes part in the negative regulation of the renin-angiotensin system. It was postulated that ACE2 is the main target of SARS-CoV-2 that supports its entrance into the human cells [16]. Interestingly, the loss of ACE2 in mice results in alterations in glucose tolerance and reduces the first phase of insulin secretion [46].…”

“…According to the Human Protein Atlas [15], human proteins related to SARS-CoV-2 can be divided into three groups: SARS-CoV-2 entry receptors, SARS-CoV-2 entry associated proteases, and intracellular SARS-CoV-2 interacting proteins (https://www.proteinatlas.org/ humanproteome/sars-cov-2, accessed on 10 February 2022). The most known SARS-CoV-2 entry receptor is angiotensin-converting enzyme 2 (ACE2) [16]. Dipeptidyl peptidase-4 (DPP4) is also involved in the entry [17].…”

Therapeutic Potential of Myrrh, a Natural Resin, in Health Management through Modulation of Oxidative Stress, Inflammation, and Advanced Glycation End Products Formation Using In Vitro and In Silico Analysis

“…Under hyperglycemic conditions, advanced glycation end products (AGEs) have been found to be elevated in diabetes mellitus. It is produced by the glycation of biomolecules [2,4]. COVID-19 risk factors have been connected to AGEs [5].…”