Fig. 2.

Pathogenesis of Covid-19 in heart and β-cells through ACE-2 receptor in diabetic patients. ACE receptor converts Ang-I to Ang-II, which has detrimental effects through the RAS pathway, thereby increasing systemic oxidative stress and apoptosis leading to decrease in proliferation and insulin secretion by β-cells along with an increase in the risk of cardiovascular complications. Whereas, ACE-2 receptor has protective effect on β-cells by converting the Ang-II to Ang-(1–7) which through Mas receptor stimulates vasodilatory, anti-inflammatory and anti-fibrotic signaling and decreases oxidative stress, provides antiviral defences, increases β-cell proliferation and insulin secretion. However, Covid-19 infection reduces ACE-2 receptors on the cell surface by directly binding ACE-2 and its endocytosis, which releases suppression of RAS and in turn further reduces ACE-2 expression. Further, the cytokine storm caused due to the hyper-inflammation of the Covid-19 infection release the pro-inflammatory cytokines that activate ADAM-17 and cleave the ACE-2 receptors from the membrane surface. The cytokine storm along with the immune cell imbalance not only adversely affects the cardiac tissue and β-cells but it will cause organ dysfunction at systemic level