COVID-19 brain fog has links to brain disease: study

Cleveland Clinic researchers explore how COVID-19 infection may lead to Alzheimer's-like symptoms.

Dave Yasvinski 4 minute read June 14, 2021
covid-19 brain fog

New research has looked at cognitive symptoms associated with the virus. Getty

The cognitive issues experienced by people with long haul COVID may be caused by an overlap between the virus and the brain changes experienced by people with Alzheimer’s disease, a new study has found.

With enduring cases of COVID-19 becoming more common, researchers at the Cleveland Clinic hoped to gain a better understanding of the mechanisms by which the virus produces neurological complications. The work, published in the journal Alzheimer’s Research & Therapy, uncovered a close network relationship between the virus and Alzheimer’s, a devastating neurological disease.

“While some studies suggest that SARS-CoV-2 infects brain cells directly, others found no evidence of the virus in the brain,” said Feixiong Cheng, lead author of the study and a researcher in Cleveland Clinic’s Genomic Medicine Institute. “Identifying how COVID-19 and neurological problems are linked will be critical for developing effective preventive and therapeutic strategies to address the surge in neurocognitive impairments that we expect to see in the near future.”

Alzheimer’s disease, the most common cause of dementia, is a degenerative condition that is believed to be the result of the accumulation of certain proteins in the brain that leads to the slow death of neurons. This process eventually produces symptoms of memory loss, difficulty thinking or problem solving and changes in mood and behaviour.

Brain fog is one of the more debilitating symptoms experienced by long haulers — the term used to describe the roughly 10 per cent of COVID sufferers who still have symptoms of the virus months after infection. Like delirium and hallucinations, this form of cognitive impairment was initially believed to be the result of the fierce battle the body’s immune system is waging against the virus.

“It’s a kind of mental cloudiness — like you’re in a daze,” said Joseph Khabbaza, a pulmonary and critical care physician at the Cleveland Clinic. “You hear a lot about it with mild outpatients, but we also see it more severely in the ICU. Hallucinations and confusion are commonly experienced during all sorts of severe illnesses. When you have a kind stressor like COVID-19 in the body, you’re more likely to be confused, especially if you are elderly. This symptom is very common with older people as the body is trying to fight off an infection.”

To explore the relationship between the virus and neurological diseases, researchers used artificial intelligence to map underlying similarities across conditions. They measured the distance between SARS-CoV-2 genes and proteins with those from different neurological diseases, with closer proximity indicative of shared disease pathways. They also looked at any genetic factors that might allow the virus to directly affect brain tissue or cells.

Although they were unable to find evidence the virus was targeting the brain, they found COVID-19 has a close network relationship with multiple neurological diseases — most notably Alzheimer’s — through which an infection could lead to dementia-like symptoms. They then searched for associations between the virus and the types of neuroinflammation and microvascular injury seen in the brains of Alzheimer’s sufferers.

“We discovered that SARS-CoV-2 infection significantly altered Alzheimer’s markers implicated in brain inflammation and that certain viral entry factors are highly expressed in cells in the blood-brain barrier,” Cheng said. “These findings indicate that the virus may impact several genes or pathways involved in neuroinflammation and brain microvascular injury, which could lead to Alzheimer’s disease-like cognitive impairment.”

Genetics may also play a role in the process as individuals with the allele APOE E4/E4 — the greatest genetic risk factor for Alzheimer’s disease — enjoy less robust response from antiviral defence genes that may make them more likely to contract the virus.

“Ultimately, we hope to have paved the way for research that leads to testable and measurable biomarkers that can identify patients at the highest risk for neurological complications with COVID-19,” Cheng said.

Dave Yasvinski is a writer


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