Abstract
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.
Keywords: Low-molecular weight heparin, Neutrophil extracellular traps (NETs), Matrix metalloproteinase-9 (MMP-9), SARS-CoV-2, Venous thromboembolism (VTE)