SARS-CoV-2 infection and diabetes: Pathophysiological mechanism of multi-system organ failure

Figure 1 Possible mechanism of diabetes and severe acute respiratory syndrome coronavirus 2-induced pulmonary dysfunction. Hyperglycemia and insulin resistance in diabetes is associated with impaired cell signaling, oxidative stress, inflammation, and altered metabolism and subsequently lead to the manifestation of pulmonary dysfunction due to increased airway hyperresponsiveness, fibrosis, autonomic neuropathy, T helper 2, mast cell degranulation, Inflammatory macrophage, airway smooth muscle cell proliferation, deposition of extracellular matrix in the lung tissue, epithelial-mesenchymal transition, whereas reduced mucociliary clearance, respiratory muscle strength and synthesis of SP-A and SP-D. On the other hand, platelet or complement activation, endothelial damage, and inflammation in severe acute respiratory syndrome coronavirus 2 infection lead to the pathogenesis of pulmonary dysfunction due to elevated thrombosis, IL-6, IL-8, procoagulants, fibrosis, vasoconstriction, pulmonary edema, and angiogenesis. IR: Insulin resistance; NFκB: Nuclear factor-κB; PKC: Protein kinase C; PI3K: Phosphoinositide 3-kinases; STAT3: Signal transducer and activator of transcription 3; CTGF: Connective tissue growth factor; TGFβ: Transforming growth factor beta; Rho/RocK: Ras homologous/Rho-associated coiled-coil kinase; ROS: Reactive oxygen species; RNS: Reactive nitrogen species; RCS: Reactive carbonyl species; AGE: Advanced glycation end products; NOX: Nitrogen oxides; Ang II: Angiotensin II; Th2: T helper 2; SMC: Smooth muscle cell; ECM: Extracellular matrix; SP-A: Surfactant proteins A; SP-D: Surfactant proteins D; FFA: Free fatty acid; LDL: low-density lipoprotein; NADPH: Reduced nicotinamide adenine dinucleotide phosphate; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.