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.