Research Finds Blood Vessel Damage, Inflammation in the Brains of COVID-19 Patients

In a recent study at the National Institutes of Health (NIH), researchers consistently observed signs of damage on the brain scans of patients who died after contracting coronavirus disease 2019 (COVID-19). This damage was found to be caused by thinning and leaky blood vessels in brain tissue.

Additionally, the researchers noted that they observed no signs of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the brain tissue samples, which suggests that the damage was not a result of a direct attack on the brain by the virus, according to the study.

"We found that the brains of patients who contract infection from SARS-CoV-2 may be susceptible to microvascular blood vessel damage. Our results suggest that this may be caused by the body's inflammatory response to the virus" said study senior author Avindra Nath, MD, the clinical director at the NIH's National Institute of Neurological Disorders and Stroke, in a press release. "We hope these results will help doctors understand the full spectrum of problems patients may suffer so that we can come up with better treatments."

Although COVID-19 is a disease that primarily attacks the respiratory system, it also has had effects on patients’ neurological health, causing occurrences of headaches, delirium, cognitive dysfunction, dizziness, fatigue, and loss of the sense of smell. Some patients may even experience strokes and other neuropathologies.

However, how COVID-19 attacks the brain is still not entirely understood. Research has shown that the disease can cause inflammation and blood vessel damage, with 1 study showing evidence of small amounts of SARS-CoV-2 in some patients' brains.

In order to understand the impact of COVID-19 on patients’ neurological health, NIH researchers analyzed the brain tissue samples from 19 patients aged 5 through 73 years who had died after being treated for COVID-19 between March and July 2020. Patient samples were provided by the Office of the Chief Medical Examiner in New York City and the department of pathology at the University of Iowa College of Medicine.

All of the patients included in the study had died within a few hours to 2 months following reporting symptoms of COVID-19. Many of the patients had at least 1 risk factor for COVID-19, including diabetes, obesity, and cardiovascular disease. Of the total 19 patients, 8 had been found dead in their homes or in public settings, whereas 3 others had collapsed and died suddenly.

Using a high-powered magnetic resonance imaging (MRI) scanner that is 4 to 10 times more sensitive than most MRI scanners, the researchers analyzed patients’ olfactory bulb and brainstem samples, which are regions believed to be susceptible to COVID-19.

The results of the scans demonstrated a multitude of hyperintensities, which appear as bright spots on the scan. Bright spots are often an indication of inflammation, whereas dark spots on scans, termed hypointensities, generally show locations of bleeding, according to the study.

After examining these hyperintensities further under a microscope, the researchers found that these spots contained thinner than normal blood vessels. Additionally, they observed certain occurrences of these thin blood vessels leaking blood proteins, such as fibrinogen, into the brain. Such leakage appeared to have triggered an immune response, causing the surrounding area to fill with T cells from the blood and the brain that are called microglia.

However, when any occurrences of hypointensities were observed more closely, the researchers found that these dark spots included both clotted and leaky blood vessels with no signs of an immune reaction having been present.

"We were completely surprised. Originally, we expected to see damage that is caused by a lack of oxygen. Instead, we saw multifocal areas of damage that is usually associated with strokes and neuroinflammatory diseases," Nath said in the press release.

Additionally, the researchers did not observe infection in the brain tissue samples from the patients, despite using several methods in order to detect SARS-CoV-2 genetic material or proteins.

"So far, our results suggest that the damage we saw may not have been not caused by the SARS-CoV-2 virus directly infecting the brain," Nath said in the press release. "In the future, we plan to study how COVID-19 harms the brain's blood vessels and whether that produces some of the short- and long-term symptoms we see in patients."

REFERENCE

NIH study uncovers blood vessel damage & inflammation in COVID-19 patients' brains but no infection. Bethesda, MD: National Institute of Neurological Disorders and Stroke; December 30, 2020. eurekalert.org/pub_releases/2020-12/nion-nsu122920.php. Accessed January 7, 2021.