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[Preprint]. 2021 Aug 24:2021.01.18.21250041. Originally published 2021 Jan 20. [Version 6] doi: 10.1101/2021.01.18.21250041

Endothelial cell-activating antibodies in COVID-19

Hui Shi, Yu Zuo, Sherwin Navaz, Alyssa Harbaugh, Claire K Hoy, Alex A Gandhi, Gautam Sule, Srilakshmi Yalavarthi, Kelsey Gockman, Jacqueline A Madison, Jintao Wang, Melanie Zuo, Yue Shi, Michael D Maile, Jason S Knight, Yogendra Kanthi
PMCID: PMC7836141  PMID: 33501469

ABSTRACT

Objective

Endothelial dysfunction has been implicated in the widespread thrombo-inflammatory complications of coronavirus disease-19 ( COVID-19 ), although the upstream mediators of endotheliopathy remain cryptic. Our aim was to identify circulating factors contributing to endothelial cell activation and dysfunction in COVID-19.

Methods

Human endothelial cells were cultured in the presence of sera or plasma from 244 patients hospitalized with COVID-19 and plasma from 100 patients with non-COVID sepsis. Cell adhesion molecules (E-selectin, ICAM-1 and VCAM-1) were quantified by in-cell ELISA.

Results

Sera and plasma from patients with COVID-19, and to a lesser extent from patients with sepsis, increased surface expression of cell adhesion molecules. 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 sera markedly restrained upregulation 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 suggest that some patients with COVID-19 have potentially diverse antibodies that drive endotheliopathy, adding important context regarding thrombo-inflammatory effects of autoantibodies in severe COVID-19.

Full Text Availability

The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.


Articles from medRxiv are provided here courtesy of Cold Spring Harbor Laboratory Preprints

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