Increased platelet activation and platelet-monocyte aggregates formation associate with poor outcome in severe COVID-19 patients.
Platelets from severe COVID-19 patients induce monocyte tissue factor expression through P-selectin and integrin αIIb/β3 signaling.
Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is an emergent pathogen responsible for the coronavirus disease 2019 (COVID-19). Since its emergence, the novel coronavirus has rapidly achieved pandemic proportions causing remarkably increased morbidity and mortality around the world. A hypercoagulability state has been reported as a major pathologic event in COVID-19, and thromboembolic complications listed among life-threatening complications of the disease. Platelets are chief effector cells of hemostasis and pathological thrombosis. However, the participation of platelets in the pathogenesis of COVID-19 remains elusive. This report demonstrates that increased platelet activation and platelet-monocyte aggregates formation is observed in severe COVID-19 patients, but not in patients presenting mild COVID-19 syndrome. In addition, exposure to plasma from severe COVID-19 patients increased the activation of control platelets ex vivo. In our cohort of COVID-19 patients admitted to the ICU, platelet-monocyte interaction was strongly associated with TF expression by the monocytes. Platelet activation and monocyte TF expression were associated with markers of coagulation dysfunction as fibrinogen and D-dimers, and were increased in patients requiring invasive mechanical ventilation or patients that evolved with in-hospital mortality. Finally, platelets from severe COVID-19 patients were able to induce TF expression ex vivo in monocytes from healthy volunteers, a phenomenon that was inhibited by platelet P-selectin neutralization or integrin αIIb/β3 blocking with the aggregation inhibitor abciximab. Altogether, these data shed light on new pathological mechanisms involving platelet activation and platelet-dependent monocyte TF expression, which were associated with COVID-19 severity and mortality.