The Role of P-Selectin in COVID-19 Coagulopathy: An Updated Review

Abstract

In severe COVID-19, which is characterized by blood clots and neutrophil-platelet aggregates in the circulating blood and different tissues, an increased incidence of cardiovascular complications and venous thrombotic events has been reported. The inflammatory storm that characterizes severe infections may act as a driver capable of profoundly disrupting the complex interplay between platelets, endothelium, and leukocytes, thus contributing to the definition of COVID-19-associated coagulopathy. In this frame, P-selectin represents a key molecule expressed on endothelial cells and on activated platelets, and contributes to endothelial activation, leucocyte recruitment, rolling, and tissue migration. Briefly, we describe the current state of knowledge about P-selectin involvement in COVID-19 pathogenesis, its possible use as a severity marker and as a target for host-directed therapeutic intervention.

Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19

“…In our trial of patients with moderate COVID-19 levels, the baseline levels of plasma P-selectin were 34 ± 14 ng/mL for the placebo group and 30 ± 20 ng/mL for the crizanlizumab group. These levels are higher than levels reported for healthy control subjects in other studies ( 35 ). Nevertheless, it is possible that crizanlizumab could be more effective at decreasing inflammatory and thrombotic biomarkers in a study group with even higher levels of P-selectin.…”

“…P-selectin levels have been shown to be higher in subjects with severe COVID-19 than in those with moderate COVID-19. However, reports of P-selectin levels in subjects with moderate COVID-19 are variable, with some reports showing P-selectin levels higher in moderate COVID-19 than in control subjects and other reports showing similar levels in moderate COVID-19 and control subjects ( 35 ). The cause of such differences between studies include the following: different assays for P-selectin, potential differences in serum versus plasma levels of P-selectin, different definitions of “moderate” COVID-19, and some reports measuring soluble P-selectin and others measuring platelet-expressed P-selectin.…”

P‐ and E‐ selectin in venous thrombosis and non‐venous pathologies

“…Selectins, including P‐selectin, E‐selectin, and L‐selectin, are a family of calcium‐dependent lectins (glycoproteins) that are expressed on the surface of platelets, endothelial cells and leukocytes. They are important mediators of leukocyte and immune cell adherence and transmigration into sites of inflammation and facilitate and augment thrombosis by modulating neutrophil and monocyte activity 17 …”

Possible Role of P-selectin Adhesion in Long-COVID: A Comparative Analysis of a Long-COVID Case Versus an Asymptomatic Post-COVID Case

“…Most investigators report elevated levels of P-Selectin in SARS-CoV-2 positive patients, with seemingly larger elevation of P-selectin in more severe disease states. However, a number of studies also report comparable levels of P-selectin in COVID-19 patients and healthy controls [18].…”