To Your Health: Even Mild Cases Of COVID-19 Leave A Mark On The Brain!

Part-time Telluride local, Dr. Alan Safdi, is a world-renowned internist and gastroenterologist with encyclopedic knowledge of mind-body wellness and preventative medicine. He posts regularly on Telluride Inside… and Out under the banner of “To Your Health.” Dr. Alan’s blogs feature the most current information in his fields: health, wellness and longevity.

Links to Dr. Alan’s other podcasts and narratives on COVID-19 and more are here.

For this week’s column, Dr. Alan curated a story about the sobering fact that preliminary research finds  even mild cases of COVID-19 leave a mark on the brain. And while it is not yet clear how long the effects last, there are hints from the past.

“Some viruses such as COVID-19 can pass the blood-brain barrier—a semipermeable layer of cells that separates the central nervous system from the body’s circulation,” explains Dr. Alan. “We can learn a lot from the 1918 influenza pandemic. Svenn-Erik Mamelund, PhD. looking at asylum hospitalizations in Norway from 1872 to 1929, Mamelund found that the number of first-time hospitalized patients with mental disorders attributed to influenza increased by an average annual factor of 7.2 in the 6 years following the pandemic. In addition, he pointed out that Spanish flu survivors reported sleep disturbances, depression, mental distraction, dizziness, and difficulties coping at work. 

“Once inside the brain, viruses can infect cells or the myelin sheaths and kill them. Viruses don’t necessarily have to enter the brain to cause damage, though. They can also spark an immune response that activates microglia, which then consume otherwise healthy neurons.

“One of the earliest links between influenza and neural dysfunction was a correlation between the 1918 Spanish flu, caused by a subtype called H1N1, and an epidemic of Parkinson’s a few decades later. In the 1940s and early 1950s, diagnoses of the neurodegenerative disease appeared to increase abruptly, from 1–2 percent of the US population to 2.5-3 percent which is basically a 50 percent increase in Parkinson’s disease.”

For more information, penned by Jessica Bernard, Associate Professor, Texas A&M University, read on. 

With more than 18 months of the pandemic in the rearview mirror, researchers have been steadily gathering new and important insights into the effects of COVID-19 on the body and brain. These findings are raising concerns about the long-term impacts the coronavirus might have on biological processes such as aging.

As a cognitive neuroscientist, my past research has focused on understanding how normal brain changes related to aging affect people’s ability to think and move – particularly in middle age and beyond. But as more evidence came in showing that COVID-19 could affect the body and brain for months or longer following infection, my research team became interested in exploring how it might also impact the natural process of aging.

Peering in at the brain’s response to COVID-19:

In August 2021, a preliminary, but large-scale study investigating brain changes in people who had experienced COVID-19 drew a great deal of attention within the neuroscience community.

In that study, researchers relied on an existing database called the UK Biobank, which contains brain imaging data from over 45,000 people in the U.K. going back to 2014. This means – crucially – that there was baseline data and brain imaging of all of those people from before the pandemic.

The research team analyzed the brain imaging data and then brought back those who had been diagnosed with COVID-19 for additional brain scans. They compared people who had experienced COVID-19 to participants who had not, carefully matching the groups based on age, sex, baseline test date and study location, as well as common risk factors for disease, such as health variables and socioeconomic status.

The team found marked differences in gray matter – which is made up of the cell bodies of neurons that process information in the brain – between those who had been infected with COVID-19 and those who had not. Specifically, the thickness of the gray matter tissue in brain regions known as the frontal and temporal lobes was reduced in the COVID-19 group, differing from the typical patterns seen in the group that hadn’t experienced COVID-19.

In the general population, it is normal to see some change in gray matter volume or thickness over time as people age, but the changes were larger than normal in those who had been infected with COVID-19.

Interestingly, when the researchers separated the individuals who had severe enough illness to require hospitalization, the results were the same as for those who had experienced milder COVID-19. That is, people who had been infected with COVID-19 showed a loss of brain volume even when the disease was not severe enough to require hospitalization.

Finally, researchers also investigated changes in performance on cognitive tasks and found that those who had contracted COVID-19 were slower in processing information, relative to those who had not.

While we have to be careful interpreting these findings as they await formal peer review, the large sample, pre- and post-illness data in the same people and careful matching with people who had not had COVID-19 have made this preliminary work particularly valuable.

What do these changes in brain volume mean?

Early on in the pandemic, one of the most common reports from those infected with COVID-19 was the loss of sense of taste and smell.

Strikingly, the brain regions that the U.K. researchers found to be impacted by COVID-19 are all linked to the olfactory bulb, a structure near the front of the brain that passes signals about smells from the nose to other brain regions. The olfactory bulb has connections to regions of the temporal lobe. We often talk about the temporal lobe in the context of aging and Alzheimer’s disease because it is where the hippocampus is located. The hippocampus is likely to play a key role in aging, given its involvement in memory and cognitive processes.

The sense of smell is also important to Alzheimer’s research, as some data has suggested that those at risk for the disease have a reduced sense of smell. While it is far too early to draw any conclusions about the long-term impacts of these COVID-related changes, investigating possible connections between COVID-19-related brain changes and memory is of great interest – particularly given the regions implicated and their importance in memory and Alzheimer’s disease.

Looking ahead

These new findings bring about important yet unanswered questions: What do these brain changes following COVID-19 mean for the process and pace of aging? And, over time does the brain recover to some extent from viral infection?

These are active and open areas of research, some of which we are beginning to do in my own laboratory in conjunction with our ongoing work investigating brain aging.

Our lab’s work demonstrates that as people age, the brain thinks and processes information differently. In addition, we’ve observed changes over time in how peoples’ bodies move and how people learn new motor skills. Several decades of work have demonstrated that older adults have a harder time processing and manipulating information – such as updating a mental grocery list – but they typically maintain their knowledge of facts and vocabulary. With respect to motor skills, we know that older adults still learn, but they do so more slowly than young adults.

When it comes to brain structure, we typically see a decrease in the size of the brain in adults over age 65. This decrease is not just localized to one area. Differences can be seen across many regions of the brain. There is also typically an increase in cerebrospinal fluid that fills space due to the loss of brain tissue. In addition, white matter, the insulation on axons – long cables that carry electrical impulses between nerve cells – is also less intact in older adults.

As life expectancy has increased in the past decades, more individuals are reaching older age. While the goal is for all to live long and healthy lives, even in the best-case scenario where one ages without disease or disability, older adulthood brings on changes in how we think and move.

Learning how all of these puzzle pieces fit together will help us unravel the mysteries of aging so that we can help improve quality of life and function for aging individuals. And now, in the context of COVID-19, it will help us understand the degree to which the brain may recover after illness as well.

We need to learn from history and the 1918 pandemic can teach us a lot.

Dr. Alan Safdi:

Dr. Alan Safdi is board-certified in Internal Medicine and in Gastroenterology and is a Fellow of the American College of Gastroenterology. A proven leader in the healthcare arena, he has been featured on the national program, “Medical Crossfire” and authored or co-authored numerous medical articles and abstracts.

Safdi, a long-time Telluride local, has been involved in grant-based and clinical research for four decades. He is passionate about disease prevention and wellness, not just fixing what has gone wrong.

Dr. Alan is an international lecturer on the subjects of wellness, nutrition and gastroenterology.

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