Researchers at Stanford University have found signs of inflammation in the brains of people who died of COVID-19.News center

The most comprehensive molecular study to date on the brains of people who died of COVID-19 revealed unmistakable signs of inflammation and brain circuit damage.

Researchers at Stanford University School of Medicine and Saarland University in Germany report that what they see is very similar to what was observed in the brains of people who died of neurodegenerative conditions such as Alzheimer’s disease and Parkinson’s disease. doing.

The findings may help explain why many COVID-19 patients report neurological problems. These complaints are increased in more severe cases of COVID-19. And they can survive as an aspect of “long COVID”. This is a long-term disorder that can occur after infection with SARS-CoV-2, the virus that causes COVID-19. About one-third of individuals hospitalized with COVID-19 say they report vague thoughts, forgetting, poor concentration, and symptoms of depression. Tony Wis Korey, PhD, Professor of Neurology and Neuroscience, Stanford University.

Still, researchers couldn’t find any signs of SARS-CoV-2 in the brain tissue from eight individuals who died of the disease. Brain samples from 14 people who died from other causes were used as controls in the study.

“The brains of patients who died of severe COVID-19 showed serious molecular markers of inflammation, even with no reported clinical signs of neuropathy,” said Wyss-Coray, Professor DH Chen II. Says.

Scientists disagree on whether SARS-CoV-2 is present in the brains of patients with COVID-19. “We used the same tools they used, and other more definitive tools, and really looked for the presence of the virus,” he said. “And we couldn’t find it.”

A treatise explaining the research will be published on June 21st. Nature.. Wyss-Coray shares a senior author with Dr. Andreas Keller, Chair of Clinical Bioinformatics at Saarland University.The first author is Andrew Yang, PhD, a postdoctoral fellow in the Wyss-Coray group, and a graduate student in the Fabian Kern, Keller group.

Blood-brain barrier

The blood-brain barrier consists of some of the tightly sewn blood vessel cells and a mass-like pier created by the protrusions of the brain cells pressed against the blood vessels, which until recently were generated outside the brain. Cells and molecules.

However, previous studies by the Wyss-Coray group and other researchers have shown that extracerebral blood-mediated factors can signal through the blood-brain barrier and ignite an inflammatory response in the brain. I am. This is because, as Wyss-Coray and his colleagues discovered, blood factors in young mice activate cognitive abilities in older mice, whereas blood in older mice adversely affects the mental abilities of younger peers. Explain why you might give it.

Our findings may help explain long COVID brain fog, malaise, and other neurological and psychiatric symptoms.

When hearing reports of persistent neurological symptoms in some COVID-19 patients, Wyss-Coray had problems similar to those caused by SARS-CoV-2 infection due to aging and various neurodegenerative diseases. I was interested in what could cause it. Other studies have also seen conflicting reports of the virus being present in brain tissue, so he wanted to know if the virus actually invaded the brain.

According to Wyss-Coray, it is difficult to find the brain tissue of patients with COVID-19. Neuropathologists are reluctant to take the necessary steps for resection because they may be exposed to SARS-CoV-2 and regulations often prohibit such procedures to prevent viral infections. It is a target. However, Keller, who worked at the Wyss-Coray Lab as a visiting professor at Stanford University, was able to access COVID-19 brain tissue samples from autopsy performed at a hospital associated with Saarland University.

Scientists have recorded activation levels of thousands of genes in each of 65,309 individual cells taken from brain tissue samples of COVID-19 patients and controls using an approach called single-cell RNA sequencing. did.

Signs of distress in neurons of the cerebral cortex

The activation levels of hundreds of genes in all major cell types in the brain differed between the brains of COVID-19 patients and the controls. Many of these genes are involved in the inflammatory process.

Neurons in the cerebral cortex also showed signs of distress. The cerebral cortex is a region of the brain that plays an important role in decision making, memory, and mathematical reasoning. Most of these neurons are of two types, excitatory and inhibitory, and form complex logic circuits that perform these higher brain functions.

The outermost layers of the cerebral cortex of patients who died of COVID-19 show molecular changes suggestive of inhibition of signaling by excitatory neurons and enhanced signaling by inhibitory neurons that act like brakes on excitatory neurons. I did. This type of signaling imbalance is associated with neurodegenerative conditions such as cognitive impairment and Alzheimer’s disease.

An additional finding was that peripheral immune cells, called T cells, which are immune cells that roam the pathogen, were significantly abundant in the brain tissue of dead COVID-19 patients. In a healthy brain, these immune cells are rare.

“Viral infections appear to cause a systemic inflammatory response that can cross the blood-brain barrier and cause inflammatory signaling, which in turn can cause neuroinflammation of the brain,” Wyss-Coray said. Mr. says.

“Many COVID-19 patients, especially those who report or show neurological problems, or who are hospitalized, may have these neuroinflammation markers found in those who died of the disease. There is, “he added. By analyzing the cerebrospinal fluid of these patients, it may be possible to know that its content reflects to some extent the content of the living brain.

“Our findings may help explain the neurological and psychiatric symptoms of brain fog, malaise, and other long COVIDs,” he said.

Wyss-Coray is a co-director of Paul F. Glenn Aging Biology Research Center, Stanford UniversityMembers of Stanford Bio-X, Stanford Maternal and Child Health Research Institute,and Utsai Institute for Neuroscience At Stanford University ChEM-H..

Other Stanford co-authors of this study are postdoctoral researchers Dr. Patricia Rosada, Dr. Nicholas Shaum, Dr. Ryan Best, Dr. Nannan Lou, and Dr. Oliver Hahn. Dr. Daniela Beldnick, a basic life research scientist. Life Sciences Research Experts Maayan Agam and Kurti Calcuttawala; Former Life Sciences Researcher Davis Lee. Former visiting student researcher Christina Mart. Divya Channappa, an expert in life science research; Dr. Davidgate, a neurology and neuroscience instructor. M. Windy McNerney, PhD, Clinical Associate Professor of Psychiatry and Behavioral Sciences. And Associate Professor of Imma Cobos, MD, PhD, Pathology.

In addition to Keller and Kahn, other researchers at Saarland University also contributed to this study.

This study was funded by the Nomis Foundation, National Institutes of Health (Grants T32-AG0047126, 1RF1AG059694, and P30AG066515), Nan Fung Life Sciences, Wu Tsai Neurosciences Institute, and Stanford Alzheimer’s Disease Research Center.