Fig. 1

The pathophysiology of SARS-CoV-2 infection. SARS-CoV-2, via its surface spike protein, binds to the human ACE2 receptor after spike protein activation by TMPRSS2. This results in down-regulation of ACE2 and increased angiotensin II levels and consequently increased plasminogen activator inhibitor C-1 expression and reduced fibrinolysis. The disease it causes is associated with an increase in inflammatory cytokines and coagulation disorders, with predisposition to thrombus formation. Mononuclear cells interact with activated platelets and the coagulation cascade, which activate 1 inflammatory cells by binding thrombin and tissue factor with specific protease activated receptors and by binding fibrin to Toll-like receptor 4. The activation of inflammatory cells results in the release of pro-inflammatory cytokines, leading to impairment of the natural coagulation pathways and shut down of fibrinolysis. This state of hyper inflammation and hypercoagulability leads to multiple organ dysfunction, most commonly affecting the lungs, heart and kidneys. ACE2 angiotensin-converting enzyme-2, aPTT activated partial thromboplastin time, ARDS acute respiratory distress syndrome, COVID-19 coronavirus disease 2019, HFpEF heart failure preserved ejection fraction, HFrEF, heart failure reduced ejection fraction, IL interleukin, PAR protease-activated receptor, PT prothrombin time, SARS-COV-2severe acute respiratory syndrome coronavirus 2, TMPRSS2 transmembrane protease serine, TLR4 Toll-like receptor 4, TNFα tumor necrosis factor-α