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Monitoring Changes in Human Umbilical Vein Endothelial Cells upon Viral Infection Using Impedance-Based Real-Time Cell Analysis
Published on: May 5, 2023
Endothelial Cell-Activating Antibodies in COVID-19
Hui Shi1, Yu Zuo2, Sherwin Navaz2
1University of Michigan, Ann Arbor, and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Insights
COVID-19 serum activates endothelial cells, contributing to thromboinflammation. This is driven by specific antibodies, particularly antiphospholipid antibodies, which promote endothelial cell activation and dysfunction in severe cases.
Area of Science:
- Immunology
- Vascular Biology
- Infectious Diseases
Background:
- Endothelial dysfunction is a key feature of severe COVID-19, leading to thromboinflammatory complications.
- The specific factors causing COVID-19-related endotheliopathy are largely unknown.
Purpose of the Study:
- To identify circulating factors in COVID-19 that activate and cause dysfunction in endothelial cells.
- To investigate the role of antibodies in COVID-19-induced endotheliopathy.
Main Methods:
- Endothelial cells were exposed to serum/plasma from COVID-19 and sepsis patients.
- Expression of cell adhesion molecules (E-selectin, VCAM-1, ICAM-1) was measured.
- The impact of antiphospholipid antibodies and IgG was assessed.
Main Results:
- COVID-19 serum/plasma significantly increased cell adhesion molecule expression.
- Elevated soluble ICAM-1 and E-selectin correlated with disease severity.
- Antiphospholipid antibodies in COVID-19 serum were potent drivers of endothelial activation; IgG depletion reduced this effect.
Conclusions:
- Specific antibodies in some COVID-19 patients can drive endotheliopathy.
- These findings highlight the role of autoantibodies in severe COVID-19 thromboinflammation.
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.
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