Could it be that COVID-19 impacts the brain via microvascular blood vessel damage but not by direct viral infection? That’s the likely explanation based on recent National Institute of Health (NIH) sponsored research, led by Avindra Nath, MD, clinical director at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS). In a bid to help clinicians better understand the disease and its impact on patients, this in-depth study focused on how COVID-19 affects a patient’s brain. The results, which were published as a correspondence in the New England Journal of Medicine, reveal that the researchers consistently spotted hallmarks of damage caused by thinning and leaky brain blood vessels in tissue samples from patients who died shortly after contracting the disease. But they also found no signs of SARS-CoV-2 in the tissue samples: this suggests that the damage wasn’t caused by a direct viral attack on the brain.
The Quest to understand COVID-19
Although COVID-19 is primarily a respiratory disease, patients often experience neurological challenges, such as headaches, delirium, cognitive dysfunction, dizziness, fatigue, and loss of sense of smell. The disease, reports the NIH in its recent press release may also trigger strokes and other neuropathologies in patients infected by the pathogen.
Evidence for Blood Vessel Damage
Several studies reveal that COVID-19 can trigger inflammation and blood vessel damage. In one study, researchers found evidence of small amounts of SARS-CoV-2 in some patients’ brains. However, scientists still are at the early stages in the effort to comprehend in its totality how this disease affects the brain.
NIH researchers, led by Dr. Nath, conducted an in-depth examination of brain tissue samples from 19 patients who had passed away during to COVID-19 between March and July 2020. Samples of 16 of the patients were provided by the Office of the Chief Medical Examiner in New York City while the other 3 cases were provided by the department of Pathology at the University of Iowa College of Medicine in Iowa City.
These patients died at a wide range of ages, from 5 to 73 years old. They died within a few hours to a couple months after reporting symptoms. Many patients had one or more risk factors, including diabetes, obesity, and cardiovascular disease. Eight of the patients were found dead at home or in public settings. Another three patients collapsed and died suddenly.
Initially, the research team used a special, high-powered magnetic resonance imaging (MRI) scanner that is 4 to 10 times more sensitive than most MRI scanners for the examination of samples of the olfactory bulbs and brainstems from each patient.
These regions are considered, at least early on, as significantly susceptible to COVID-19. Olfactory bulbs control the sense of smell while the brainstem controls breathing and heart rate. These scans showed that both regions had an abundance of bright sports, called hyperintensities, often indicating inflammation, and dark spots known as hypointensities, indicating bleeding.
Then using these scans as a guide, the researchers examined the sports more carefully under a microscope. They found that the bright spots contained blood vessels that were thinner than normal and sometimes leaking blood proteins, such as fibrinogen, into the brain. This appeared to trigger some form of immune reaction. The spots were surrounded by T cells from the blood and the brain’s own immune cells called microglia. In contrast, the dark sports contained both clotted and leaky blood vessels but no immune response.
Investigator Point of View: Some Surprises
Dr. Nath reported that “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” he shared. Dr. Nath continued, “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.”
Nath and team were actually surprised by the findings assuming that COVID-19 associated damage would be caused by a lack of oxygen rather than what they actually uncovered: “…multifocal areas of damage that is usually associated with strokes and neuroinflammatory diseases.”
This study was funded by the NIH Intramural Research Program at NINDS; as it turns out, NINDS is the nation’s leading funder of research on the brain and nervous system.
Avindra Nath, MD, clinical director at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS
Call to Action: The team reports Dr. Nath will pursue a research question centering on how SARS-CoV-2 serves as an agent harming the brain’s blood vessels and how this may trigger observed symptoms.