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SARS-CoV-2, the virus that causes COVID-19, disrupts the blood-brain barrier.

COVID-19 is widely regarded as a respiratory illness, but evidence suggests it affects multiple organ systems, including the central nervous system. For example, some people with COVID-19 experience headaches, nausea, vomiting, or “brain fog” – indicators of neurological involvement. Evidence from a 2020 study suggests that SARS-CoV-2, the virus that causes COVID-19, disrupts the blood-brain barrier.

SARS-CoV-2 enters cells via the angiotensin-converting enzyme 2 (ACE2), a protein that is widespread among the body’s tissues and plays important roles in blood pressure control. Once inside the cell, SARS-CoV-2 replicates, triggering a robust immune response and eliciting widespread inflammation.

The blood-brain barrier, a semi-permeable barrier that separates the blood from the brain’s extracellular fluid, prevents the entry of neurotoxic substances into the brain. Disruption of the blood-brain barrier has been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, among others.

The investigators first examined postmortem brain tissue from healthy people as well as people who had been diagnosed with hypertension (high blood pressure) or dementia to identify the presence of ACE2 in the brain blood vessels. They found that not only was ACE2 present in the blood vessels, but it was particularly abundant in people with hypertension or dementia. Then, using an in vitro model of the blood-brain barrier, they assessed the effects of exposure to the SARS-CoV-2 spike protein, the primary infectious particle on the virus. They found that exposure to the spike protein impaired blood-brain barrier function and integrity. Finally, using a tissue model that mimics the movement of fluid in the barrier, they found that the spike protein increased barrier permeability.

These findings suggest that SARS-CoV-2 binds to ACE2 receptors in the brain and impairs blood-brain barrier function and integrity. These effects may be exacerbated in people with co-existing illnesses such as hypertension or dementia.

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