NIH researchers detect brain damage in COVID-19 patients, despite no brain infection

In an in-depth study, NIH researchers consistently found vascular damage in the brains of COVID-19 patients, but no signs of SARS-CoV-2 infections. Here is a high resolution scan of a patient’s brain stem. Arrows point to light and dark spots indicating damage to blood vessels observed in the study. Credit: Thanks to NIH / NINDS

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 affecting a patient’s brain, researchers at the National Institutes of Health have consistently seen signs of damage caused by thinning and leaking cerebral blood vessels in tissue samples from patients who died shortly after contracting the disease. In addition, they saw no signs of EARS-CoV-2 in the tissue samples, indicating that the damage was not caused by a direct viral attack on the brain. The results were published as a 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. said. “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 taken by the office of the chief medical examiner in New York City, while the other three cases by the pathology department at University of Iowa College of Medicine, Iowa City. The patients die at a wide range of ages, 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, powerful magnetic resonance imaging (MRI) 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 had an abundance of bright spots, called hyperintensities, which often indicate inflammation, and dark spots, called hypointensities, that represent bleeding.

The researchers then use the scans as a guideline to examine the stains 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 immune cells of the brain called microglia. In contrast, the dark spots contain both clotted and leaking blood vessels, but no immune response.

“We were completely amazed. 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 damages the brain’s blood vessels and whether it produces some of the short- and long-term symptoms we see in patients.”

Reference: “Microvascular Injury in Brain Patients with COVID-19” by 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., December 30, 2020, New England Journal of Medicine.
DOI: 10.1056 / NEJMc2033369

This study was supported by NIH Intramural Research Program at the National Institute of Neurological Disorders and Stroke (NS003130) and an NIH grant (NS109284).

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