ABSTRACT
Objectives
Patients with coronavirus disease 19 ( COVID-19 ) are at high risk for fibrin-based occlusion of vascular beds of all sizes. Considering endothelial cell activation has regularly been described as part of the COVID-19 thrombo-inflammatory storm, we aimed to find upstream mediators of this activation.
Methods
Cultured endothelial cells were exposed to sera from 118 unique patients hospitalized with COVID-19. Surface adhesion markers E-selectin, ICAM-1, and VCAM-1 were detected by in-cell ELISA.
Results
We found modest correlations between serum NET remnants (cell-free DNA, myeloperoxidase-DNA complexes, citrullinated histone H3) and upregulation of surface E-selectin, VCAM-1, and ICAM-1 on endothelial cells. A more robust predictor of the ability of COVID-19 serum to activate endothelial cells was the presence of circulating antiphospholipid antibodies, specifically anticardiolipin IgG and IgM and anti-phosphatidlyserine/prothrombin (anti-PS/PT) IgG and IgM. Depletion of total IgG from anticardiolipin-high and anti-PS/PT-high samples markedly restrained upregulation of E-selectin, VCAM-1, and ICAM-1. At the same time, supplementation of control serum with patient IgG was sufficient to trigger endothelial cell activation.
Conclusions
These data are the first to reveal that patient antibodies are a driver of endothelial cell activation in COVID-19 and add important context regarding thrombo-inflammatory effects of autoantibodies in severe COVID-19.
KEY MESSAGES
What is already known about this subject?
Patients with COVID-19 are at high risk for fibrin-based occlusion of vascular beds of all sizes. Endothelial cell activation has regularly been described as part of the COVID-19 thrombo-inflammatory storm.
What does this study add?
The presence of circulating antiphospholipid antibodies is a robust predictor of the ability of COVID-19 serum to activate endothelial cells.
Purified COVID-19 IgG with high levels of anticardiolipin and anti-PS/PT antibodies trigger a pro-adhesive phenotype in endothelial cells.
How might this impact on clinical practice or future developments?
Patients with may be screened for antiphospholipid antibodies to evaluate their risk of thrombosis and progression to respiratory failure.
Patients with high antiphospholipid antibody titers might benefit from treatments used in traditional cases of severe APS such as therapeutic anticoagulation, corticosteroids, and plasmapheresis.
Full Text Availability
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