A team of UMass Memorial Health Care physicians has embarked on a two-year study looking and whether COVID-19 triggers inflammation in the brain that in turn causes brain matter to start to break down, leading to dementia.
The group consists of Dr. Douglas T. Golenbock, chief of the Division of Infectious Diseases and Immunology at UMass Medical School; Michael Heneka, professor of medicine at UMass Medical School and a senior researcher and Director of Neurodegenerative Diseases and Gerontopsychiatry at the University of Bonn; and Dr. Robert Brown, Leo P. and Theresa M. LaChance Chair in Medical Research at UMass Medical School.
Using funding National Institutes of Health, the three researchers will closely follow 40 people who contracted COVID-19 and subject them to series of brain MRIs, as well as neuropsychiatric and immune system tests to assess changes in cognition and gather physical evidence, demonstrated in blood-based biomarkers, of dementia — an umbrella term for all diseases of the brain marked by the impairment of at least two brain functions.
“We believe COVID-19 infection causes neuroinflammation, which in turn causes a decline in cognitive capability and loss of brain matter,” Golenbock told MassLive.
If true, Golenbock says the respiratory infection can lead to the acceleration of conditions like Alzheimer’s and Parkinson’s disease.
And the idea that COVID infection can actually damage brain tissue is not exactly a novel one. Numerous studies have demonstrated that patients with severe COVID-19 who end up needing ICU care often exhibited symptoms of cognitive decline during their bout of illness. A study published by researchers at Northwestern Medicine dating back to October found that more than 80% of 509 hospitalized COVID patients had “neurologic manifestations.”
Such manifestations range from seemingly harmless disordered taste and smell, symptoms that have been widely reported by COVID sufferers, to full-blown encephalopathy, a disease of the brain marked by alterations to its structure, which roughly one-third of patients developed in the study.
In fact, there is a growing body of evidence that neurological effects in COVID patients are more common than once thought. Episodes of delirium have been observed in critically ill COVID patients in Europe and the United States at unusually high rates — so much so researchers have thought about making part of the disease’s diagnostic criteria.
The group says that COVID-associated dementia may be closely connected to the experience of so-called COVID “long haulers” — patients who report symptoms months after infection, including brain fog and feeling fatigued. A study published in the Annals of Clinical and Translational Neurology in March found that more than 80% of COVID long haulers who were not hospitalized reported experiencing brain fog among a host of other neurological symptoms.
Their primary neurological symptoms included brain fog, which was present in 81% of patients; headache, present in 68%; and numbness/tingling, present in 60%. A little more than half of the patients reported a persistent loss of taste or smell and muscle aches that involve the body’s soft tissue — tendons, ligaments, and connective tissue, according to the study.
The point of interest for the team of UMass researchers begins with one central process: inflammation. The group proposed the COVID-dementia link after learning that COVID patients can experience an exaggerated immune response to the infection called a “cytokine storm,” a potentially fatal condition of multi-system inflammation caused by the release of an excess of small proteins called cytokines that act as messengers for the immune system.
The phenomenon is also thought to have played a part in what made the Spanish flu so deadly during the 1918 influenza pandemic, according to the New England Journal of Medicine. The bacterial infection Yersinia pestis, responsible for the Black Death that swept through Eurasia in the 14th century, also triggers the overproduction of cytokines, resulting in the cytokine storm, according to NEJM.
Heneka said the study will look at the underlying pathogenesis of the posited COVID-associated dementia, building on his own research that suggests immune reactions in the brain can play a role in the development of diseases like Alzheimer’s.
It’s possible, Heneka says, that COVID initiates a completely new neurodegenerative process, or accelerates already existing disease. Dementia can begin in the brain “years if not decades” before the onset of symptoms — a problem that continues to vex scientists studying the origins of the phenomenon.
“Is it a transient function, or a true neurodegenerative process — that remains to be seen,” Heneka said.
In Germany, where Heneka resides, COVID patients often call into the University of Bonn’s memory clinic complaining of memory problems, loss of concentration and unusual tiredness. He says a 35-year-old who had a very minor bout of COVID was recently seen by neurologists for dementia-like symptoms. It’s cases like these that have experts concerned about how much is still unknown about the virus.
Of course, the challenge of getting a proper scientific handle on the link between COVID and dementia requires long-term study of patients. So the results may not be in for years, if not decades. But postmortem analyses of the brain tissue in COVID patients have shown that the structural changes are real.
It is has also been shown, Heneka says, that the virus can directly invade the brain.
“There is direct (brain) invasion in very few cases, so there is obviously a way,” Heneka said. “There is probably a route to the brain through the olfactory system.”
The group stressed that while they hope the study will lead to a greater understanding behind the origins of cognitive decline in COVID patients, it’s important that scientists continue to develop therapies to combat the virus.
And one thing that’s at least helped long haulers feel better has been getting the vaccine, which new research suggests helps to clear up brain fog and other symptoms, according to NPR.
“There are reports of people recovering from the fatigue after vaccination,” Heneka said.