Abstract
Objective: While endothelial dysfunction has been implicated in the widespread thromboinflammatory complications of COVID-19, the upstream mediators of endotheliopathy remain, for the most part, unknown. This study was undertaken to identify circulating factors contributing to endothelial cell activation and dysfunction in COVID-19.
Methods: Human endothelial cells were cultured in the presence of serum or plasma from 244 patients hospitalized with COVID-19 and plasma from 100 patients with non-COVID-19-related sepsis. Cell adhesion molecules (E-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 [ICAM-1]) were quantified using in-cell enzyme-linked immunosorbent assay.
Results: Serum and plasma from COVID-19 patients increased surface expression of cell adhesion molecules. Furthermore, levels of soluble ICAM-1 and E-selectin were elevated in patient serum and correlated with disease severity. The presence of circulating antiphospholipid antibodies was a strong marker of the ability of COVID-19 serum to activate endothelium. Depletion of total IgG from antiphospholipid antibody-positive serum markedly reduced the up-regulation of cell adhesion molecules. Conversely, supplementation of control serum with patient IgG was sufficient to trigger endothelial activation.
Conclusion: These data are the first to indicate that some COVID-19 patients have potentially diverse antibodies that drive endotheliopathy, providing important context regarding thromboinflammatory effects of autoantibodies in severe COVID-19.
【초록키워드】 COVID-19, IgG, severe COVID-19, endotheliopathy, antibody, disease severity, Human, Sepsis, E-selectin, ICAM-1, Endothelial dysfunction, Endothelium, serum, Patient, plasma, expression, marker, Endothelial cell, COVID-19 patient, autoantibody, cell adhesion molecule, adhesion molecules, dysfunction, endothelial, Activation, Factor, Depletion, circulating, complications of COVID-19, upstream, while, Effect, widespread, Cell, enzyme-linked immunosorbent, identify, elevated, reduced, correlated, contributing to, activate, implicated, quantified, intercellular, patients hospitalized, vascular cell adhesion, with COVID-19, 【제목키워드】 COVID-19,