SARS-CoV-2 does not directly infect the brain, but can cause neurological damage

SARS-CoV-2, the virus that causes COVID-19, may not directly infect the brain, but it is still a critical nerve, according to a new study by neuropathologists, neurologists, and neuroradiologists at the Columbia Medical School. It may cause physiologic damage. ..

“There was considerable debate about whether the virus could infect the brain, but we couldn’t find any signs of the virus in the brain cells of more than 40 COVID-19 patients,” said James, a professor of pathology. E. Goldman, Doctor of Medicine, said. Cell biology ( Psychiatry), Professor of Pathology and Cell Biology, Peter D. Canoll, MD, PhD, and Kiran T, Associate Professor of Neurology, Winifred Mercer Pitkin. He led the research with Thakur and MD.

“At the same time, we saw many pathological changes in these brains, which is why critically ill patients experience confusion, delirium, and other serious neurological effects, and mildly ill patients from weeks to on. Explain why you are experiencing “brain fog” for several months. “”

Studies published in the journal brainIs the largest and most detailed COVID-19 brain autopsy report ever published, and the most common neurological changes in these patients are inflammation caused by viruses in other parts of the body or cerebrovascular disease. It suggests that it may be caused.

There is no virus in the brain cells

The study examined the brains of 41 COVID-19 patients who died of the disease during hospitalization. Patients ranged in age from 38 to 97 years. About half were intubated and all had lung damage from the virus. Most of the patients were Hispanic. Hospitals vary in length, with some dying shortly after arriving in the emergency room and others hospitalized for several months. All patients underwent extensive laboratory and laboratory studies, and some underwent MRI and CT scans of the brain.

To detect viruses in brain neurons and glial cells, researchers used multiple methods, including RNA in situ hybridization, which can detect viral RNA in intact cells. An antibody that can detect viral proteins in cells. RT-PCR is a highly sensitive technique for detecting viral RNA.

Despite their intensive investigation, the researchers found no evidence of the virus in the patient’s brain cells. They detected very low levels of viral RNA by RT-PCR, probably due to the virus in the soft meninges that line the blood vessels or brain.

We examined more brains than other studies and used more techniques to search for viruses. The bottom line is that no evidence of viral RNA or protein can be found in brain cells. “

James E. Goldman, MD, PhD, Professor of Pathology and Cell Biology

“Several papers claim to have found the virus in neurons and glia, but they are thought to be due to contamination, and all the virus in the brain is contained in the blood vessels of the brain.” “Brain tissue If the virus is present in the virus, it must be in very small amounts and does not correlate with the distribution or abundance of neuropathological findings, “says Canol.

Tests were conducted in more than 20 brain regions, including the olfactory bulb, because it is speculated that the coronavirus may travel from the nasal cavity through the olfactory nerve to the brain. “Again, no viral proteins or RNAs were found, but viral RNAs and proteins were found in the patient’s nasal mucosa and the high olfactory mucosa of the nasal cavity,” says Goldman. (The latter discovery is in an unpublished study of BioRxiv, led by Associate Professor of Otolaryngology, Jonathan Overdevest, MD, PhD, and Professors of Biochemistry and Molecular Biophysics and Neuroscience, Stavros Lomvardas, PhD. It is appearing.)

Signs of hypoxic damage and nerve cell death

In all patients, researchers found significant brain pathology, despite the absence of the virus in the brain. It falls into two main categories.

“The first thing we noticed was in many areas damaged by lack of oxygen,” says Goldman. “It’s not surprising that there is hypoxic damage in the brain, as they all had severe lung disease.”

Some of these were large areas caused by strokes, but most were very small and could only be detected with a microscope. Based on other characteristics, researchers found that these small areas of hypoxic damage were caused by blood clots, which are common in patients with severe COVID-19, who temporarily stopped supplying oxygen to that area. I think it was.

Even more surprising findings, according to Goldman, were the large number of activated microglia found in the brains of most patients. Microglia are immune cells that reside in the brain and can be activated by pathogens.

“We have discovered a process called the“ neuronal esophagus, ”a cluster of microglia that attacks neurons,” says Canol. Microglia may have been activated by inflammatory cytokines such as interleukin-6 associated with SARS-CoV-2 infection because no virus was detected in the brain.

“At the same time, hypoxia can induce the expression of” eating “signals on the surface of neurons, making hypoxic neurons more vulnerable to activated microglia,” says Canol. Damage to the brain. “

This group was one of the first autopsies described by pathology and cell biology instructors Osama Al-Dalahmah, MD, PhD in a case report published at Acta Neuropathologica Communications last March. I found a pattern of pathology. Over the next few months, when neuropathologists performed more COVID brain autopsies, they saw similar findings many times, which were prominent and common neuropathological findings in patients who died of COVID. I noticed that.

Activated microglia were found primarily in the heart and respiratory rhythms, the lower brainstem, which regulates consciousness levels, and the hippocampus, which is involved in memory and mood.

“We know that microglial activity leads to the loss of neurons, and that loss is permanent,” says Goldman. “Is there enough neuronal loss in the hippocampus to cause memory loss, or in other parts of the brain that help us to focus our attention? That’s possible, but we really don’t know at this point.”

Persistent neurological problems in survivors

Goldman states that further research is needed to understand why some patients after COVID-19 continue to experience symptoms.

Researchers are currently examining and detailing autopsy of patients who died months after recovering from COVID-19.

They also examined the brains of patients with acute respiratory distress syndrome (ARDS) prior to the COVID-19 pandemic to determine how much of the COVID-19 brain condition was the result of severe lung disease. Checking it up.