Further Findings Concerning Endothelial Damage in COVID-19 Patients

Monica Gelzo,Marika Comegna,Giuseppe Castaldo,Roberto Parrella,Gabriella Fabbrocini,Gustavo Cernera,Biagio Pinchera,Annunziata De Rosa,Mauro Mormile,Ivan Gentile,Filippo Scialò,Gaetano Corso,Sara Cacciapuoti

doi:10.3390/biom11091368

Abstract

Systemic vascular damage with micro/macro-thrombosis is a typical feature of severe COVID-19. However, the pathogenesis of this damage and its predictive biomarkers remain poorly defined. For this reason, in this study, serum monocyte chemotactic protein (MCP)-2 and P- and E-selectin levels were analyzed in 204 patients with COVID-19. Serum MCP-2 and P-selectin were significantly higher in hospitalized patients compared with asymptomatic patients. Furthermore, MCP-2 increased with the WHO stage in hospitalized patients. After 1 week of hospitalization, MCP-2 levels were significantly reduced, while P-selectin increased in patients in WHO stage 3 and decreased in patients in WHO stages 5–7. Serum E-selectin was not significantly different between asymptomatic and hospitalized patients. The lower MCP-2 levels after 1 week suggest that endothelial damage triggered by monocytes occurs early in COVID-19 disease progression. MCP-2 may also predict COVID-19 severity. The increase in P-selectin levels, which further increased in mild patients and reduced in severe patients after 1 week of hospitalization, suggests that the inactive form of the protein produced by the cleavage of the active protein from the platelet membrane is present. This may be used to identify a subset of patients that would benefit from targeted therapies. The unchanged levels of E-selectin in these patients suggest that endothelial damage is less relevant.

Highlights

We studied the levels of P- and E-selectin and monocyte chemotactic protein (MCP)-2 in serum samples from COVID-19 patients with varying severities, i.e., asymptomatic and hospitalized patients in different phases of the disease
The comparison of the three biomarkers between asymptomatic and hospitalized patients showed that MCP-2 and P-selectin levels were significantly higher (p < 0.001) in hospitalized patients (Figure 1A,B), while the differences observed for E-selectin were not significant (Figure 1C)
Our data suggest that serum MCP-2 represents an effective biomarker for COVID-19 severity and therapy monitoring as a result of its rapid kinetics

Summary

Introduction

Endothelial activation has been reported in patients with severe COVID-19 [1]. It is triggered by inflammatory cytokines released by leukocytes and contributes to generating systemic micro- and macro-thrombosis [2]. Tissue factor [3] and platelet activation [4] contribute. The pathogenesis of endothelial damage during severe COVID-19 remains poorly defined. A better knowledge of the molecular events involved in its pathogenesis may contribute to selecting appropriate therapeutic targets [2,5]. Necroscopies of COVID-19 patients revealed endothelial inflammation with the accumulation of lymphocytes and monocytes in the majority of important organs [6,7], the lungs [8]

Methods

Results

Discussion

Conclusion