COVID-19 may not actually infect the brain, but neurological damage persists: study

TORONTO -- Does COVID-19 impact the brain? The answer is both yes and no, according to a new study which suggests the virus likely doesn’t infect the brain itself.

The study, conducted by specialists at Columbia University Vagelos College of Physicians and Surgeons and published in the journal Brain on Thursday, found that while the patients examined did not have significant traces of the virus in their brain cells, they still sustained neurological damage from the virus.

“We were unable to find any signs of virus inside brain cells of more than 40 COVID-19 patients," James E. Goldman, professor at Columbia University and lead author of the study, said in a press release.

"At the same time, we observed many pathological changes in these brains, which could explain why severely ill patients experience confusion and delirium and other serious neurological effects--and why those with mild cases may experience 'brain fog' for weeks and months."

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It has been observed since the beginning of the pandemic that many patients have developed neurological symptoms after contracting COVID-19, but not much research has looked at the virus within the brain.

This recent study looked 41 people who had died from the virus at a medical centre in New York City. The average age was 74, and researchers obtained family consent to perform autopsies in order to study the brain.

One fifth of those studied had died from the virus within 24 hours of arriving at hospital, and many of the patients had a comorbidity such as Parkinson’s disease, dementia or mild cognitive impairment (MCI).

Every brain was examined by at least two neuropathologists. Researchers examined the brains for viral RNA and viral proteins, using a variety of methods, and focusing on different sections of the brain.

One area they examined was the olfactory section of the brain, to investigate a theory that the virus could travel to the brain through the nasal cavity. While viral particles were found in the nasal cavity, researchers didn’t find any that had made their way into the brain.

Goldman mentioned in the release that some other studies looking at a smaller number of brains have claimed to find traces of the virus in brain cells, but maintained that their findings suggest “if there's any virus present in the brain tissue, it has to be in very small amounts and does not correlate with the distribution or abundance of neuropathological findings.”

If the virus isn’t reaching the brain itself in large enough quantities to affect it, why are we seeing these neurological impacts in COVID-19 victims?

Researchers say the damage comes down to a few factors. One main issue is hypoxia. When the body is struggling to take in oxygen, different areas of the body are starved of the proper amount of oxygen. This can occur in the brain of as a result of severe COVID-19.

Every single brain studied had hypoxic damage, the research stated.

"The first thing we noticed was a lot of areas with damage from a lack of oxygen," Goldman says. "They all had severe lung disease, so it's not surprising that there's hypoxic damage in the brain."

Other things associated with severe COVID-19, such as strokes and blood clots, can also cut off oxygen to the brain.

But another finding was that specific immune cells in the brain, called microglia, were activated in these COVID-19 patients. Researchers believe these immune cells were wrongfully attacking neurons, and theorized that it could be due to inflammatory proteins associated with virus infection.

"At the same time, hypoxia can induce the expression of 'eat me' signals on the surface of neurons, making hypoxic neurons more vulnerable to activated microglia," Peter D. Canoll, professor of pathology and cell biology, said in the release. “So even without directly infecting brain cells, COVID-19 can cause damage to the brain."

The sections in the brain most affected by the microglia were lower brainstem areas that regulate heart and breathing rhythms, as well as the hippocampus, which governs things such as memory and mood.

If neurons are attacked by microglia, their loss is permanent, Goldman said, which could cause memory problems down the line.

Interestingly, despite the fact that the study included people who had battled the virus for a range of time periods before dying, including some from days to weeks, “neuropathological findings did not appear to correlate with time of hospitalization,” the research stated, suggesting that interventions at the hospital did not have a significant impact on the type of neurological damage researchers were seeing.

Many COVID-19 long-haulers report experiencing neurological symptoms such as “brain fog” for months after other symptoms clear up, and the study’s authors say more research into these issues could help understand how to treat these lingering affects.

“It is important to consider the potential impact of the neuropathological changes we, and others, have found in autopsies if such changes are present in the brains of patients who survive COVID-19,” the research said.

As the research was done through autopsies, researchers acknowledge that this means the findings reflect severe cases of COVID-19, and may not be directly applicable to more mild cases.

Moving forward, the researchers will be investigating the brains of more COVID-19 patients who died of the virus under different circumstances, such as those who died months after recovering from COVID-19 and those who experienced acute respiratory distress syndrome (ARDS) prior to their death, in order to get a better picture of how the virus affects the brain.