NIH examine exhibits immune response to COVID-19 could harm mind

July 05, 2022

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Antibodies produced in response to COVID-19 could mistakenly goal cells important to the blood-brain barrier, which may trigger bleeds and clots in sufferers and enhance the chance for stroke, researchers reported in Mind.

“Sufferers usually develop neurological problems with COVID-19, however the underlying pathophysiological course of is just not nicely understood,” Avindra Nath, MD, medical director of the Nationwide Institute of Neurological Issues and Stroke and coauthor of the examine, mentioned in an NIH press launch. “We had beforehand proven blood vessel harm and irritation in sufferers’ brains at post-mortem, however we didn’t perceive the reason for the harm. I believe on this paper we’ve gained vital perception into the cascade of occasions.”

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Nath and colleagues examined mind tissue from 9 sufferers, aged 24 to 73 years, who died between March and July 2020 throughout the pandemic and who examined constructive for SARS-CoV-2 earlier than or after dying. All sufferers confirmed indicators of blood vessel harm within the mind on postmortem MRI. Researchers assessed neuroinflammation and immune responses utilizing immunohistochemistry and in contrast affected person samples with 10 non-COVID controls.

The examine, which was funded by NIH, exhibits that antibodies generated in response to COVID-19 are concerned in an assault on the cells that line the mind’s blood vessels, which results in irritation and harm. Moreover, the researchers reported that SARS-CoV-2 was not detected within the mind, which suggests the virus doesn’t have an effect on the mind immediately.

Nath and colleagues discovered that the antibodies goal tightly packed endothelial cells that type the blood-brain barrier, which retains dangerous cells from reaching the mind, whereas permitting obligatory substances to cross via. Injury to the endothelial cells in blood vessels within the mind can result in a leakage of proteins from the blood, which may trigger bleeds and clots.

Based on the discharge, this examine builds on earlier analysis, which discovered proof of mind harm brought on by thinning and leaking blood vessels.

The researchers reported that an antibody-mediated assault activated endothelial cells, which specific proteins known as adhesion molecules that trigger platelets to stay collectively. Excessive ranges of adhesion molecules had been present in endothelial cells within the tissue samples.

“Activation of the endothelial cells brings platelets that follow the blood vessel partitions, inflicting clots to type and leakage to happen. On the similar time the tight junctions between the endothelial cells get disrupted, inflicting them to leak,” Nath mentioned within the launch. “As soon as leakage happens, immune cells akin to macrophages could come to restore the harm, establishing irritation. This, in flip, causes harm to neurons.”

Nath and colleagues reported that in areas with endothelial cell harm, greater than 300 genes confirmed a lower in expression, whereas six genes had been elevated. These genes had been related to oxidative stress, DNA harm and metabolic dysregulation.

“It’s fairly attainable that this similar immune response persists in lengthy COVID sufferers, leading to neuronal harm,” Nath mentioned. “There might be a small indolent immune response that’s persevering with, which signifies that immune-modulating therapies may assist these sufferers. So, these findings have crucial therapeutic implications.”

Reference:

NIH. Small NIH examine reveals how immune response triggered by COVID-19 could harm the mind. https://www.nih.gov/news-events/news-releases/small-nih-study-reveals-how-immune-response-triggered-covid-19-may-damage-brain. Revealed July 5, 2022. Accessed July 5, 2022.

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