Figure 1: Thromboinflammation in COVID-19
(1) SARS-CoV-2 binds via the human angiotensin-converting enzyme 2 (ACE-2) receptor expressed on the endothelial surface. The virus activates monocytes releasing a cytokine storm (including interleukin [IL]-6, IL-1β, IL-2, IL-6, IL-7, IL-8, IL-10, IL-17, TNF-α, chemokine ligand-2 (CCL2), CCL3, interferon gamma-inducible protein, C-X-C motif chemokine ligand-10, and monocyte chemoattractant protein-1, all of which correlate with adverse clinical outcomes.(2) The inflammatory effects of cytokines also activate vascular endothelial cells, disrupting endothelial function and integrity, which leads to increased platelet and neutrophil recruitment.(3) Increased neutrophil at inflammatory site results in increased expression of adhesion molecules such as L-selectin, P-selectin, intracellular adhesion molecule-1, on endothelial cells. Activated neutrophils release their neutrophil extracellular traps (NETs, which contain a backbone of DNA and citrullinated histone [H3Cit], cathepsin G, and neutrophil elastase [NE]) which trap platelets, increasing their activation and aggregation, this in turn further activates neutrophils to produce more NETs. (4) This cycle of events triggers coagulation cascade activation which in turn increases fibrin formation and thrombosis.