News Release
Wednesday 30 December 2020
Results from a study of 19 deceased patients suggest that brain damage is a by-product of a patient’s disease.
In an in-depth study of how COVID-19 affects a patient’s brain, researchers from the National Institutes of Health have consistently seen characteristics of damage caused by thinning and leaking cerebral blood vessels in tissue samples from patients who died shortly after taking the contracted disease. In addition, they did not see any signs of SARS-CoV-2 in the tissue samples, suggesting that the damage was not caused by a direct viral attack on the brain. The results were published as correspondence in the New England Journal of Medicine.
‘We found that the brains of patients infected with SARS-CoV-2 may be susceptible to damage to microvascular blood vessels. Our results suggest that it may be caused by the body’s inflammatory response to the virus, ”said Avindra Nath, MD, clinical director at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and senior author of the study. . “We hope these results will help physicians understand the full spectrum of problems patients may experience so that we can devise better treatments.”
Although COVID-19 is primarily a respiratory disease, patients experience neurological problems including headache, delirium, cognitive dysfunction, dizziness, fatigue, and loss of the sense of smell. The disease can also cause patients to develop stroke and other neuropathologies.
Several studies have shown that the disease can cause inflammation and damage to blood vessels. In one of these studies, the researchers found evidence of small amounts of SARS-CoV-2 in the brains of some patients. Nevertheless, scientists are still trying to understand how the disease affects the brain.
In this study, the researchers conducted an in-depth examination of brain tissue samples from 19 patients who died after experiencing COVID-19 between March and July 2020. Samples of 16 of the patients were provided by the chief medical examiner’s office in New York City, while the other three cases were provided by the Department of Pathology at the University of Iowa College of Medicine, Iowa City. The patients died at a wide age from 5 to 73 years old. 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 at home or in the public area. Three more patients collapsed and died suddenly.
Initially, the researchers used a special, MRI (magnetic resonance imaging) scanner that is 4 to 10 times more sensitive than most MRI scanners, to examine samples of each patient’s olfactory bulbs and brainstems. These regions are thought to be highly susceptible to COVID-19. Olfactory bulbs control our sense of smell while the brain stem controls our breathing and heart rate. The scans revealed that both regions have an abundance of bright spots, called hyperintensities, which often indicate inflammation, and dark spots, called hypointensities, which represent bleeding.
The researchers then use the scans as a guideline to examine the spots under a microscope more closely. They found that the bright spots contained blood vessels that were thinner than normal and sometimes leaked blood proteins, such as fibrinogen, into the brain. This apparently caused an immune response. The spots are surrounded by T cells from the blood and the brain’s own immune cells called microglia. In contrast, the dark spots contain both clotted and leaking blood vessels, but no immune response.
“We were completely surprised. Originally we expected to see damage caused by a lack of oxygen. Instead, we have seen multifocal areas of damage that are usually associated with strokes and neuro-inflammatory diseases, ”said Dr. Nath said.
Finally, the researchers saw no signs of infection in the brain tissue samples, although they used several methods to detect genetic material or proteins of SARS-CoV-2.
“So far, our results suggest that the damage we saw may not have been caused by the SARS-CoV-2 virus that directly infected the brain,” said Dr. Nath said. “In the future, we plan to study how COVID-19 harms the brain’s blood vessels and whether it produces some of the short- and long-term symptoms we see in patients.”
This study was supported by NIH Intramural Research Program at the National Institute of Neurological Disorders and Stroke (NS003130) and an NIH grant (NS109284).
NINDS (https://www.ninds.nih.gov) is the country’s leading funder for research into the brain and nervous system. The mission of NINDS is to acquire fundamental knowledge about the brain and nervous system and use that knowledge to reduce the burden of neurological diseases.
About the National Institute for Aging (NIA): NIA leads the U.S. federal government to conduct and support research on aging and the health and well-being of older people. Learn more about age-related cognitive change and neurodegenerative diseases via the NIA’s Alzheimer’s website and related dementia education and referral (ADEAR). Visit the main NIA website for more information on a wide range of aging topics and stay connected.
About the National Institutes of Health (NIH):
NIH, the country’s medical research agency, contains 27 institutes and centers and is part of the U.S. Department of Health and Human Services. NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, investigating the causes, treatments, and drugs for common and rare diseases. Visit www.nih.gov for more information on NIH and its programs.
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Article
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, 30 December 2020 DOI: 10.1056 / NEJMc2033369.