NIH researchers consistently found blood vessel damage in the brains of COVID-19 patients, but no signs of SARS-CoV-2 infection. Arrows point to light and dark spots that indicate damage to the blood vessels observed in the study. NIAID
Results from a study of 19 deceased patients suggest that brain damage is a by-product of a patient’s illness.
In an in-depth study of how COVID-19 affects a patient’s brain, researchers at the National Institutes of Health consistently found traces of damage from thinning and leaking in tissue samples from patients who died shortly after contracting the disease Cerebral blood vessels were caused. Additionally, they saw no signs of SARS-CoV-2 in the tissue samples, suggesting that the damage was not caused by a direct virus attack on the brain. The results were published as correspondence in the New England Journal of Medicine.
We found that the brains of patients who become infected with SARS-CoV-2 can be prone to microvascular blood vessel damage. Our results suggest that this may be caused by the body’s inflammatory response to the virus. We hope these results will help doctors understand the full spectrum of problems patients may suffer so that we can find better treatments.
Avindra Nath, MD, clinical director at the National Institute for Neurological Disorders and Stroke, NIH and lead author on the study.
Although COVID-19 is primarily a respiratory disease, patients often experience neurological problems including headache, delirium, cognitive dysfunction, dizziness, fatigue, and loss of sense of smell. The disease can also cause patients to experience strokes and other neuropathologies.
Several studies have shown that the disease can cause inflammation and blood vessel damage. In one of these studies, the researchers found evidence of low levels of SARS-CoV-2 in the brains of some patients. Even so, scientists are still trying to understand how the disease affects the brain.
In this study, researchers conducted an in-depth examination of brain tissue samples from 19 patients who contracted COVID-19 between March and July 2020. Samples from 16 patients were provided by the chief physician’s office in New York City, while the other 3 cases were provided by the Department of Pathology at the University of Iowa College of Medicine, Iowa City. Patients died in a broad age range from 5 to 73 years. They died within hours to two 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 in their homes or in public. Another three patients collapsed and died suddenly.
First, the researchers used a special high-performance magnetic resonance imaging (MRI) scanner, four to ten times more sensitive than most MRI scanners, to examine samples of each patient’s olfactory bulb and brainstem. It is believed that these regions are very susceptible to COVID-19. Smelling bulbs control our sense of smell, while the brain stem controls our breathing and heart rate. The scans showed that both regions had an abundance of light spots called hyperintensities, which are often indicative of inflammation, and dark spots, called hypointensities, which represent bleeding.
The researchers then used the scans as a guide to examine the spots more closely under a microscope. They found that the bright spots contained blood vessels that were thinner than normal and that sometimes leaked blood proteins such as fibrinogen into the brain. This seemed to trigger an immune response. The spots were surrounded by T cells from the blood and the brain’s own immune cells called microglia. In contrast, the dark spots contained both clotted and leaky blood vessels, but no immune response.
We were totally surprised. Originally we expected damage caused by a lack of oxygen. Instead, we saw multifocal areas of damage that are usually associated with stroke and neuroinflammatory diseases.
Ultimately, the researchers saw no signs of infection in the brain tissue samples, despite using various methods to detect genetic material or proteins from SARS-CoV-2.
So far, our results suggest that the damage we’ve seen may not have been caused by the SARS-CoV-2 virus, which is directly infecting the brain. Going forward, we want to study how COVID-19 damages the blood vessels in the brain and whether this causes some of the short and long-term symptoms we see in patients.
This study was supported by the NIH Intramural Research Program at the National Institute for Neurological Disorders and Stroke (NS003130) and an NIH grant (NS109284).
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Lee MH, Perl DP, Nair G, Li W, Maric D, Murray H, Dodd SJ, Koretsky AP, Watts JA, Cheung V, Masliah E, Horkayne-Szakaly I, Jones R, Stram MN, Moncur J, Hefti M, Folkerth RD, Nath A. Microvascular injury in the brain of patients with COVID-19. New England Journal of Medicine, December 30, 2020 DOI: 10.1056 / NEJMc2033369.