August 16, 2022

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How COVID-19 immune response damages the brain?

How COVID-19 immune response damages the brain?



 

How COVID-19 immune response damages the brain?

The study results from the National Institutes of Health (NIH) could shed light on the long-term neurological symptoms of COVID-19.

New research describes an immune response triggered by COVID-19 infection that damages blood vessels in the brain and can lead to short- and long-term neurological symptoms.

 

How COVID-19 immune response damages the brain?

 

 

In an NIH study published in Brain, researchers from the National Institute of Neurological Disorders and Stroke (NINDS) examined brain changes in nine people who died suddenly after contracting the virus.

 

Scientists have found evidence that antibodies — proteins produced by the immune system in response to viruses and other invaders — are involved in attacks on cells lining blood vessels in the brain, which lead to inflammation and damage.

Consistent with the group’s earlier research, SARS-CoV-2 was not detected in the patients’ brains, suggesting that the virus did not directly infect the brain.

 

Understanding how SARS-CoV-2 infection triggers brain damage may help develop treatments for those patients with COVID-19 who present with lingering neurological symptoms.

 

“Patients frequently present with neurological complications of COVID-19, but the underlying pathophysiology is not well understood,” said Avindra Nath, MD, NINDS clinical director and senior author of the study. “We have previously shown patient brains at autopsy. Vascular damage and inflammation in vascular disease, but we don’t understand the cause of the damage. I think in this paper, we’ve gained important insights into the cascade of events.”

 

Dr. Nath and his team have discovered that antibodies produced in response to COVID-19 may mistakenly target cells critical to the blood-brain barrier.

Tight endothelial cells help form the blood-brain barrier, which prevents harmful substances from entering the brain while allowing essential substances to pass through.

Damage to endothelial cells in the blood vessels of the brain can cause proteins to leak out of the blood. This causes bleeding and blood clots in some COVID-19 patients and may increase the risk of stroke.

 

For the first time, scientists have observed deposition of immune complexes — molecules formed when antibodies bind to antigens (foreign substances) — on the surface of endothelial cells in the brains of COVID-19 patients. This immune complex can trigger inflammation and lead to tissue damage.

 

The study builds on their previous research that found evidence of brain damage caused by thinning and leaky blood vessels.

They suspect that the damage may be due to the body’s natural inflammatory response to the virus.

 

To further explore this immune response, Dr. Nath and his team examined brain tissue from a subset of patients in previous studies.

The nine people, ranging in age from 24 to 73, were selected because they showed signs of blood vessel damage in the brain based on scans of their brain structures.

These samples were compared with samples from a control group of 10.

The team looked at neuroinflammation and immune responses using immunohistochemistry, a technique that uses antibodies to identify specific marker proteins in tissues.

 

As in their earlier study, the researchers found signs of vascular leakage based on the presence of blood proteins that do not normally cross the blood-brain barrier.

This suggests that the tight junctions between endothelial cells in the blood-brain barrier are damaged.

 

Dr. Nath and his colleagues found evidence that endothelial cell damage may be due to an immune response.

These observations suggest that endothelial cells are activated by antibody-mediated attack. When endothelial cells are activated they express proteins called adhesion molecules, which in turn cause platelets to stick together.

High levels of adhesion molecules were found in endothelial cells of brain tissue samples.

 

“The activation of endothelial cells brings platelets that stick to the vessel wall and leads to clot formation and leakage. At the same time, the tight junctions between endothelial cells are disrupted, which causes them to leak,” explains Nath. “Once a leak occurs, immune cells such as macrophages may come to repair the damage and trigger inflammation. This in turn leads to damage to neurons,” said Dr.

 

The researchers found that the expression of more than 300 genes decreased in the damaged regions of the endothelial cells, while the expression of six genes increased.

These genes are associated with oxidative stress, DNA damage and metabolic dysregulation.

This may shed light on the molecular basis of neurological symptoms associated with COVID-19 and provide potential therapeutic targets.

 

Taken together, these findings provide insight into the immune response that damages the brain after COVID-19 infection.

But it remains unclear what antigen the immune response is targeting, because the virus itself was not detected in the brain.

Antibodies against the SARS-CoV-2 spike protein likely bind to the ACE2 receptor that the virus uses to enter cells. But researchers need to conduct more studies to explore this hypothesis.

 

In addition, the research could have implications for understanding and treating long-term neurological symptoms after COVID-19, including headaches, fatigue, loss of taste and smell, sleep problems, and “brain fog.” If the patients in the study survived, researchers believe they are likely to develop COVID-19.

 

Dr Nath said: “It is very likely that this same immune response persists in Long COVID patients, leading to neuronal damage. There may be a small indolent immune response going on, which means that immunomodulatory therapy may help these patients. So these findings have very important therapeutic implications.”

 

These results suggest that treatments aimed at preventing the development of the immune complexes observed in the study may be potential treatments for post-COVID neurological symptoms.

 

 

 

 

How COVID-19 immune response damages the brain?

(source:internet, reference only)


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