Coronavirus Disease (COVID)-19 and Diabetic Kidney Disease

Abstract

The present review describes COVID-19 severity in diabetes and diabetic kidney disease. We discuss the crucial effect of COVID-19-associated cytokine storm and linked injuries and associated severe mesenchymal activation in tubular epithelial cells, endothelial cells, and macrophages that influence neighboring cell homeostasis, resulting in severe proteinuria and organ fibrosis in diabetes. Altered microRNA expression disrupts cellular homeostasis and the renin-angiotensin-system, targets reno-protective signaling proteins, such as angiotensin-converting enzyme 2 (ACE2) and MAS1 receptor (MAS), and facilitates viral entry and replication in kidney cells. COVID-19-associated endotheliopathy that interacts with other cell types, such as neutrophils, platelets, and macrophages, is one factor that accelerates prethrombotic reactions and thrombus formation, resulting in organ failures in diabetes. Apart from targeting vital signaling through ACE2 and MAS, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are also associated with higher profibrotic dipeptidyl transferase-4 (DPP-4)-mediated mechanisms and suppression of AMP-activated protein kinase (AMPK) activation in kidney cells. Lowered DPP-4 levels and restoration of AMPK levels are organ-protective, suggesting a pathogenic role of DPP-4 and a protective role of AMPK in diabetic COVID-19 patients. In addition to standard care provided to COVID-19 patients, we urgently need novel drug therapies that support the stability and function of both organs and cell types in diabetes.

Machine learning and semi-targeted lipidomics identify distinct serum lipid signatures in hospitalized COVID-19-positive and COVID-19-negative patients

“…Developing screening tests and effective therapies have been the urgent issues that most studies have addressed i.e. most studies have been directed toward describing the clinical and epidemiological characteristics of COVID-19 [2] , [3] , [4] , [5] , [6] or have investigated the “cytokine storm” associated with the infection, with the urgent objective of combating the pandemic in the short term [7] , [8] while bearing in mind that COVID-19 will not be eradicated easily, and that populations would need to accommodate for the infection in the future. Indeed, although vaccination campaigns are progressing effectively in financially well-established countries, infection continues to increase rapidly in many countries that have poor health infrastructures.…”

Virtual screening of functional foods and dissecting their roles in modulating gene functions to support post COVID‐19 complications

“…This can lead to higher extracellular matrix (ECM) deposition, collagens, and accumulation of fibronectin. Inhibiting DPP‐4 counterbalances the mesenchymal transition processes and suppresses pro‐fibrotic signaling, ECM deposition, fibronectin, and collagen accumulation (Srivastava et al., 2021 ). Besides, studies also show that DPP‐4 inhibitors are proved safe in post COVID‐19 infections of patients with diabetes, and some say they also reduce mortality (Nauck & Meier, 2020 ; Roussel et al., 2021 ).…”

Molecular signaling pathways, pathophysiological features in various organs, and treatment strategies in SARS-CoV2 infection

“…Accordingly, overactive immune cells exacerbate fibrosis, apoptosis, and microvascular changes ( Ahmadian et al, 2021 , Battagello et al, 2020 ) may reduce vascular perfusion and lower the kidneys' glomerular filtration rate ( Battagello et al, 2020 ). Cytokine storms cause epithelial, endothelial, and macrophage cells to migrate to mesenchymal cells, activating the mesenchyme, podocyte cell apoptosis, and severe proteinuria ( Srivastava et al, 2021 ). Endothelial cell damage is a consequence of a cytokine storm.…”

“…Endothelial cell damage is a consequence of a cytokine storm. The fibroblasts derived from endothelial-to-mesenchymal cell transition interacted with platelets, neutrophils, and other immune cells that produce thrombosis ( Srivastava et al, 2021 )…”

“…SARS-CoV-2 infects kidney podocytes, resulting in proteinuria and the spread of pro-inflammatory cytokines such as transforming growth factor (TGF), platelet-derived growth factor (PDGF), interferon-gamma, interleukin, vascular endothelial growth factors (VEGF), and chemokine ligand 1 (CXCL1). Sclerosis, hyalinosis, and the deposition of mesangial matrix and fibrosis may develop due to the action of these mediators' in the glomeruli ( Srivastava et al, 2021 ). Glomerular hyperfiltration leads to oxidative stress, which exacerbates glomerular injury by depositing the mesangial matrix and fibrosis.…”