U.S. NIH Study Finds That SARS-CoV-2 Induced Antiphospholipid Antibodies Causes Endothelial Cell Activation And Dysfunction Leading To Severe Covid-19 Clotting
Source: Thailand Medical News - Autonatibodies And Severe COVID-19 Blood Clotting Feb 17, 2022 1 year ago
A new study funded by the U.S. NIH that involved researchers from the University of Michigan-USA and the U.S. Lung and Blood Institute at Bethesda has found that SARS-CoV-2 antiphospholipid antibodies causes endothelial cell activation and dysfunction that often leads to severe blood clotting in COVID-19 patients.
Although endothelial dysfunction has been implicated in the widespread thrombo-inflammatory complications of COVID-19 disease, the upstream mediators of endotheliopathy remain for the most part cryptic.
The study aim was to identify circulating factors contributing to endothelial cell activation and dysfunction in COVID-19.
The study team cultured human endothelial cells that were presence in the serum or plasma of 244 patients hospitalized with COVID-19 and plasma from 100 patients with non-COVID sepsis. Cell adhesion molecules (E-selectin, VCAM-1, and ICAM-1) were quantified by in-cell ELISA.
The study findings showed that serum and plasma from patients with COVID-19 increased surface expression of cell adhesion molecules. Furthermore, levels of soluble ICAM-1 and E-selectin were elevated in patient serum and tracked with disease severity.
Importantly the presence of circulating antiphospholipid antibodies was a strong marker of the ability of COVID-19 serum to activate endothelium.
It was found that depletion of total IgG from antiphospholipid antibody-positive serum markedly restrained upregulation of cell adhesion molecules. Conversely, supplementation of control serum with patient IgG was sufficient to trigger endothelial activation.
The study findings 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.
The study findings were published in the peer reviewed journal: Arthritis & Rheumatology. https://onlinelibrary.wiley.com/doi/10.1002/art.42094
The earlier preprint version is available on MedRxiv.
The study team involved with the U.S. NIH, after analyzing blood samples from 244 patients hospitalized for COVID-19, identified "rogue antibodies" that correlate with severe illness and may help explain mechanisms associated with severe blood clotting.
The study team found circulating antiphospholipid antibodies, which can be more common among individuals with autoimmune disorders, such as lupus.
These "autoantibodies," which target a person's own organs and systems however can also be activated in response to viral infections and activate other immune responses.
The study team compared the blood samples to those from healthy controls and found the COVID-19 samples contained higher levels of the antibody IgG, which works with other immune cells, such as IgM, to respond to immune threats.
Interestingly, the higher levels of IgG were also associated with COVID-19 disease severity, such as in patients who required breathing assistance.
The study team also observed similar patterns, but to a lesser extent, after analyzing blood samples from 100 patients hospitalized for sepsis, which can leave the body in inflammatory shock following a bacterial or viral infection.
It is already known that IgG helps bridge a gap between innate and adaptive immune responses, a process that helps the body recognize, respond to, and remember danger.
Typically, in normal cases, these features help protect the body from illness and infection. But, in some cases, this response can become hyperextended or altered and exacerbate illness.
A significant finding from this study is that when the study team removed IgG from the COVID-19 blood samples, they saw molecular indicators of "blood vessel stickiness" fall. When they added these same IgG antibodies to the control samples, they saw a blood vessel inflammatory response that can lead to clotting.
Corresponding author, Dr Yogendra Kanthi from the Division of Intramural Research National Heart, Lung and Blood Institute Bethesda, Maryland, told Thailand Medical
News, “As every organ has blood vessels in it, circulating factors that lead to the ‘stickiness’ of healthy blood vessels during COVID-19 may help explain why the virus can affect many organs, including the heart, lungs, and brain.”
The key query of the study was evaluating "upstream" factors involved with severe blood clotting and inflammation among individuals with severe COVID-19 illness.
The study team notes that future studies could explore the potential benefits of screening patients with COVID-19 or other forms of critical illness for antiphospholipids and other autoantibodies and at earlier points of infection. This may help identify patients at risk for extreme blood clotting, vascular inflammation, and respiratory failure. Corresponding studies could then assess the potential benefits of providing these patients with treatments to protect blood vessels or fine-tune the immune system.
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