BACKGROUND: SARS-CoV-2 infection is associated with hypercoagulability which predisposes to venous thromboembolism (VTE).We analyzed platelet and neutrophil activation in COVID-19 patients and their association with VTE. METHODS: Hospitalized COVID-19 patients and age- and sex-matched healthy controls were studied. Platelet and leukocyte activation, neutrophil extracellular traps (NETs), and matrix metalloproteinase-9 (MMP-9), a neutrophil-released enzyme, were measured. Four patients were re-studied after recovery. The activating effect of COVID-19 plasma on control platelets and leukocytes and the inhibiting activity of common antithrombotic agents on it were studied. RESULTS: 36 COVID-19 patients and 31 healthy controls were studied; 8/36 COVID-19 patients (22.2%) developed VTE. Platelets and neutrophils were activated in COVID-19 patients. NET, but not platelet activation, biomarkers correlated with disease severity and were associated with thrombosis. Plasmatic MMP-9 was significantly increased in COVID-19 patients.Platelet and neutrophil activation markers, but less so NETs, normalized after recovery.In vitro, plasma from COVID-19 patients triggered platelet and neutrophil activation and NET formation, the latter blocked by therapeutic dose low-molecular weight heparin, but not by aspirin or dypiridamole. CONCLUSIONS: Platelet and neutrophil activation are key features of COVID-19 patients. NET biomarkers may help to predict clinical worsening and VTE, and may guide LMWH-treatment intensity.
Association of Neutrophil Activation, More Than Platelet Activation, With Thrombotic Complications in Coronavirus Disease 2019