Fig. 2: Possible contribution of hyperactivated monocytes to coagulation in COVID-19.

Circulating pro-inflammatory stimuli, such as viral pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs) and cytokines trigger activation of blood monocytes, which respond by inducing tissue factor membrane expression. Endothelial cells are activated by cytokines and viral particles and produce monocyte chemoattractants and adhesion molecules. Endothelial damage induced by the virus can also expose tissue factor on endothelial cells. Activated monocytes are recruited to endothelial cells. Tissue factor expressed by activated monocytes, monocyte-derived microvesicles and endothelial cells activates the extrinsic coagulation pathway, leading to fibrin deposition and blood clotting. Neutrophils are recruited by activated endothelial cells and release neutrophil extracellular traps (NETs), which activate the coagulation contact pathway and bind and activate platelets to amplify blood clotting. Major endogenous anticoagulant pathways, which include tissue factor pathway inhibitor (TFPI), antithrombin and protein C, are reduced further, supporting coagulation activation. CCL2, CC-chemokine ligand 2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TLR, Toll-like receptor; TNF, tumour necrosis factor; vWF, von Willebrand factor.