Platelet-monocyte interaction induces monocyte and platelet activation through TF-dependent PAR signaling. Platelet-monocyte cocultures were exposed to SARS-CoV-2 overnight in the presence of the anti-α_IIb/β₃ antibody abciximab, anti-TF clone 10H10, anti-TF clone 5G9, or isotype matched IgG. (A) The percentage of monocytes expressing TF in platelet-monocyte cocultures exposed SARS-CoV-2 in the presence of abciximab or isotype control IgG. (B) The percent inhibition on platelet-monocyte aggregate formation (CD41⁺ monocytes), monocyte CD16 expression, and cytokine release from platelets and monocytes is shown for each condition. (C) Platelet-monocyte cocultures were exposed to SARS-CoV-2 overnight in the presence the PAR1 inhibitor SCH79797, the PAR2 inhibitor AZ3451, or DMSO (vehicle). The percent inhibition on platelet-monocyte aggregate formation, monocyte CD16 expression, and cytokine release from platelets and monocytes is shown for each condition. (D) Schematic representation of platelet-monocyte signaling through P-selectin and integrin α_IIb/β₃ surface interaction and TF-mediated inflammatory amplification through PAR1 and PAR2 during severe COVID-19.