COVID-19 and Diabetes: A Comprehensive Review of Angiotensin Converting Enzyme 2, Mutual Effects and Pharmacotherapy

Abstract

The potential relationship between diabetes and COVID-19 has been evaluated. However, new knowledge is rapidly emerging. In this study, we systematically reviewed the relationship between viral cell surface receptors (ACE2, AXL, CD147, DC-SIGN, L-SIGN and DPP4) and SARS-CoV-2 infection risk, and emphasized the implications of ACE2 on SARS-CoV-2 infection and COVID-19 pathogenesis. Besides, we updated on the two-way interactions between diabetes and COVID-19, as well as the treatment options for COVID-19 comorbid patients from the perspective of ACE2. The efficacies of various clinical chemotherapeutic options, including anti-diabetic drugs, renin-angiotensin-aldosterone system inhibitors, lipid-lowering drugs, anticoagulants, and glucocorticoids for COVID-19 positive diabetic patients were discussed. Moreover, we reviewed the significance of two different forms of ACE2 (mACE2 and sACE2) and gender on COVID-19 susceptibility and severity. This review summarizes COVID-19 pathophysiology and the best strategies for clinical management of diabetes patients with COVID-19.

Patients with Diabetes Experienced More Serious and Protracted Sickness from the COVID-19 Infection: A Prospective Study

“…Serum levels of IL-6, ferritin, ESR, CRP, D-dimer and fibrinogen are significantly higher, as COVID-19 is an inflammatory and prothrombotic state [ 34 ]. An increase in ferritin, a protease enzyme associated with coronavirus entry into cells, may be the cause of increased viral replication in diabetes [ 35 ]. Patient care in diabetics should be improved to prevent morbidity issues and death [ 36 ].…”

Rational design of AAVrh10-vectored ACE2 functional domain to broadly block the cell entry of SARS-CoV-2 variants

“…However, the half-life of natural sACE2 in circulation is short ( Xie et al, 2021 ), which raises a question how to increase the level of sACE2 expression in vivo . Compared with other viral vectors, recombinant AAV has been shown as one of the most promising vectors for therapeutic gene delivery, and its efficacy has been demonstrated in extensive clinical trials, ranging from hemophilia B38 to Parkinson's disease ( Hu and Lipshutz, 2012 ; Colella et al, 2018 ; Ferreira et al, 2014 ).…”

The Pathophysiology of Long COVID throughout the Renin-Angiotensin System

“…Although no significant link was observed between the susceptibility to SARS-CoV-2 infection and diabetes, the pathology enhances the severity, the fatality rates, and complications of COVID-19 [114,115]. These outcomes raise from hyperglycemia and blood glucose fluctuations, expression of furin proteins and ACE2 receptors, ACE2 autoantibodies generation, immunological and inflammatory system imbalances, diabetes-related comorbidities, and lung injury in diabetes [116]. In human monocytes, increased plasma glucose levels and glycolysis accelerate and maintain SARS-CoV-2 replication [117], whereas increased plasma glucose levels enhance viral replication [118].…”