June 9, 2023

Revealed: How Immune Response Triggered by COVID-19 May Damage the Brain

SARS-CoV-2 infection can activate the production of immune particles that damage cells lining blood vessels in the brain, causing platelets to stick together and form embolisms. “We had formerly shown blood vessel damage and inflammation in patients brains at autopsy, but we didnt comprehend the cause of the damage. Damage to endothelial cells in blood vessels in the brain can lead to leakage of proteins from the blood. The 9 people, ranging from 24 to 73 in age, were selected because they revealed signs of blood vessel damage in the brain based on structural brain scans. Together, these findings provide insight into the immune reaction damaging the brain after COVID-19 infection.

SARS-CoV-2 infection can activate the production of immune molecules that damage cells lining blood vessels in the brain, triggering platelets to stick together and form embolisms. Blood proteins likewise leakage from the blood vessels, leading to inflammation and the damage of nerve cells. Credit: NIH Medical Arts
Findings by the NIH might provide insight into the long-term neurological symptoms of COVID-19.
New research study describes the immune action triggered by COVID-19 infection that harms the brains blood vessels and may result in short- and long-lasting neurological symptoms. In a National Institutes of Health (NIH) study published in Brain, researchers from the National Institute of Neurological Disorders and Stroke (NINDS) took a look at brain changes in 9 individuals who dropped dead after contracting the virus.
Proof that antibodies– proteins produced by the body immune system in action to viruses and other invaders– are associated with an attack on the cells lining the brains blood vessels, resulting in swelling and damage was found by the researchers. Consistent with earlier research study from the group, SARS-CoV-2 was not identified in the clients brains, recommending the virus was not directly infecting the brain.

Comprehending how SARS-CoV-2 infection can set off mental retardation might help in the development of therapies for COVID-19 patients who are experiencing sticking around neurological symptoms..
” Patients typically establish neurological complications with COVID-19, but the underlying pathophysiological process is not well comprehended,” said Avindra Nath, M.D., scientific director at NINDS and the senior author of the study. “We had formerly shown capillary damage and swelling in clients brains at autopsy, but we didnt comprehend the reason for the damage. I believe in this paper weve gained crucial insight into the waterfall of occasions.”.
Dr. Nath and his team discovered that antibodies produced in action to COVID-19 might wrongly target cells essential to the blood-brain barrier. Firmly jam-packed endothelial cells help form the blood-brain barrier, which avoids damaging compounds from reaching the brain while enabling essential substances to travel through. Damage to endothelial cells in capillary in the brain can cause leak of proteins from the blood. This causes bleeds and embolisms in some COVID-19 patients and can increase the danger of stroke.
For the first time, researchers observed deposits of immune complexes– molecules formed when antibodies bind antigens (foreign substances)– on the surface of endothelial cells in the brains of COVID-19 clients. Such immune complexes can trigger swelling, resulting in tissue damage.
The research study develops on their previous study, which found evidence of brain damage brought on by thinning and dripping capillary. They suspected that the damage might have been due to the bodys natural inflammatory response to the infection.
To even more explore this immune reaction, Dr. Nath and his group took a look at brain tissue from a subset of clients in the previous study. The 9 people, varying from 24 to 73 in age, were chosen because they revealed signs of capillary damage in the brain based upon structural brain scans. The samples were compared to those from 10 controls. The group took a look at neuroinflammation and immune actions using immunohistochemistry, a method that uses antibodies to identify specific marker proteins in the tissues.
As in their earlier research study, researchers found indications of leaky blood vessels, based on the presence of blood proteins that normally do not cross the blood-brain barrier. This suggests that the tight junctions between the endothelial cells in the blood-brain barrier are damaged.
Dr. Nath and his associates found proof that damage to endothelial cells was most likely due to an immune response– discovering deposits of immune complexes on the surface area of the cells.
These observations recommend an antibody-mediated attack that triggers endothelial cells. When endothelial cells are activated, they reveal proteins called adhesion molecules that cause platelets to stick. High levels of adhesion molecules were discovered in endothelial cells in the samples of brain tissue.
” Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing embolisms to form and leakage to take place. “Once leakage occurs, immune cells such as macrophages might come to repair the damage, setting up swelling.
Researchers discovered that in locations with damage to the endothelial cells, more than 300 genes revealed reduced expression, while 6 genes were increased. These genes were connected with oxidative tension, DNA damage, and metabolic dysregulation. This might supply hints to the molecular basis of neurological symptoms associated with COVID-19 and offer prospective healing targets.
Together, these findings give insight into the immune response damaging the brain after COVID-19 infection. It stays unclear what antigen the immune response is targeting, as the virus itself was not identified in the brain.
The research study may likewise have ramifications for understanding and dealing with long-term neurological symptoms after COVID-19, which consist of headache, tiredness, loss of taste and smell, sleep problems, and “brain fog.” Had the patients in the research study survived, the researchers think they would likely have actually developed Long COVID.
” It is quite possible that this exact same immune response continues in Long COVID patients resulting in neuronal injury,” stated Dr. Nath. “There might be a small indolent immune reaction that is continuing, which indicates that immune-modulating therapies may assist these patients. These findings have really important healing implications.”.
The outcomes suggest that treatments designed to prevent the advancement of the immune complexes observed in the research study could be prospective therapies for post-COVID neurological symptoms..
This study was supported by the NINDS Division of Intramural Research (NS003130) and K23NS109284, Roy J. Carver Foundation, and the Iowa Neuroscience Institute.