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 or plasma from 244 patients hospitalized with COVID-19 or plasma from 100 patients in the intensive care unit with sepsis. Cell adhesion molecules E-selectin, VCAM-1, and ICAM-1 were detected by in-cell ELISA. Soluble E-selectin was measured in serum. Results As compared with healthy controls, sera and plasma from patients with COVID-19, and to a lesser extent plasma from patients with sepsis, increased expression of E-selectin, VCAM-1, and ICAM-1 on cultured endothelial cells. We found modest correlations between serum neutrophil extracellular trap (NET) remnants and upregulation of cell adhesion molecules on endothelial cells. A stronger marker 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-positive and anti-PS/PT-positive 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 suggest that some patients with COVID-19 have potentially diverse antibodies that drive endothelial cell activation in COVID-19. The data also 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 may be a predictor of the ability of a patient’s total antibody profile to activate endothelial cells.Purified COVID-19 IgG with high levels of anticardiolipin and anti-PS/PT activity trigger a pro-adhesive phenotype in endothelial cells.How might this impact on clinical practice or future developments?: Patients might be screened for antiphospholipid antibodies to evaluate their risk of having an antibody profile likely to activate endothelial cells.Patients with high antiphospholipid antibody titers might benefit from treatments used in traditional cases of severe APS such as therapeutic anticoagulation, corticosteroids, and plasmapheresis.
