Plasma P-selectin is an early marker of thromboembolism in COVID-19

OBJECTIVES: The aim of this study was to explore the association of the plasma levels of coagulation proteins with venous thromboembolic events (VTE) in COVID-19 and identify candidate early markers of VTE. BACKGROUND: Coagulopathy and thromboembolism are known complications of SARS-CoV-2 infection. The mechanisms of COVID-19-associated hematologic complications involve endothelial cell and platelet dysfunction and immunothrombosis and have been intensively studied. Yet, a full understanding of the pathogenesis and factors that lead to COVID-19 associated coagulopathy is lacking. Previous studies investigated only small numbers of coagulation proteins together, and they were limited in their ability to adjust for confounders. METHODS: This study was a post-hoc analysis of a previously published dataset (Filbin et al., 2021). We included in our analysis 305 subjects with confirmed SARS-CoV-2 infection who presented to an urban Emergency Department with acute respiratory distress during the first COVID-19 surge in 2020; 13 (4.2%) were subsequently diagnosed with venous thromboembolism during hospitalization. Serial samples were obtained on days 0, 3, and 7 and assays were performed on two highly-multiplexed proteomic platforms, that in combination cover 1472 + 4776 proteins. We included 31 coagulation proteins in our analysis. RESULTS: Nine coagulation proteins were differentially expressed in patients with thromboembolic events. In multivariable models, day 0 levels of P-selectin, a cell adhesion molecule on the surface of activated endothelial cells, displayed the strongest association with the diagnosis of VTE, independent of disease severity and other confounders (p=0.0025). P-selectin together with D-dimer upon hospital presentation provided better discriminative ability for VTE diagnosis than D-dimer alone (AUROC = 0.834 vs. 0.783). CONCLUSION: Our results suggest that plasma P-selectin is a potential early biomarker for the risk stratification of VTE in COVID-19 disease. Our findings support the importance of endothelial activation in the mechanistic pathway of venous thromboembolism in COVID-19.