Why Is COVID-19 More Severe in Patients With Diabetes? The Role of Angiotensin-Converting Enzyme 2, Endothelial Dysfunction and the Immunoinflammatory System

Meta-analyses have indicated that individuals with type 1 or type 2 diabetes are atincreased risk of suffering a severe form of COVID-19 and have a higher mortality ratethan the non-diabetic population. Patients with diabetes have chronic, low-level systemicinflammation, which results in global cellular dysfunctionunderlying the wide varietyof symptoms associated with the disease, including an increased risk of respiratoryinfection. While the increased severity of COVID-19 amongstpatients with diabetesis not yet fully understood, the common features associatedwith both diseases aredysregulated immune and inflammatory responses. An additional key player in COVID-19is the enzyme, angiotensin-converting enzyme 2 (ACE2), which is essential for adhesionand uptake of virus into cells prior to replication. Changesto the expression of ACE2in diabetes have been documented, but they vary across different organs and theimportance of such changes on COVID-19 severity are still under investigation. Thisreview will examine and summarise existing data on how immune and inflammatoryprocesses interplay with the pathogenesis of COVID-19, with a particular focus on theimpacts that diabetes, endothelial dysfunction and the expression dynamics of ACE2have on the disease severity.