Figure 2.

Mechanisms associated with increased COVID-19 severity in individuals with diabetes. Coronavirus Load: SARS-CoV-2 infects the lung tissue via entry through ACE2 receptor. Individuals with diabetes have increased ACE2 receptor expression. Medications such as ACE inhibitors, GLP-1 agonists, and statins may increase ACE2 levels further. Increased glucose levels may allow SARS-CoV-2 replication. Dysregulated Immune Response: Individuals with diabetes have low chronic inflammation, which can lead to exaggerated macrophage and monocyte and T cell recruitment, promoting further inflammation in a feedback loop. Overproduction of pro-inflammatory cytokines may eventually damage the lung infrastructure. The resulting cytokine storm may initiate multiple systemic coagulation. Alveolar Dysfunction: Diabetes is associated with numerous structural changes to the lung including augmented permeability of the vasculature and reduced gas exchange. Impaired respiratory function present in individuals with diabetes may aggravate pulmonary complications, causing an increased need for mechanical ventilation in diabetes patients. Endothelial Dysfunction: In diabetes, endothelium shows markers of inflammation with increased immune cells, cytokines, potentially exacerbating the cytokine storm and pulmonary lesions. SARS-CoV2 can directly infect endothelial cells via the ACE2 receptors present on the endothelial cells. Change of vascular tone toward more vasoconstriction in diabetes patients can aggravate the subsequent organ ischemia, tissue edema, and a procoagulant state during COVID-19 infection. Coagulopathy: Individuals with diabetes have significant upregulation of hypercoagulation and fibrinolysis markers, and increased platelet activity and adhesion to endothelial wall, creating a favorable environment for thromboembolic events to occur under hyperinflammatory conditions such as SARS-CoV-2 infection. Blood clots can be detected in multiple organs.