COVID-19 Might Increase Risk for Neurodegenerative Disease

The virus inflames immune cells in the brain, preclinical research shows

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by Andrea Lobo |

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People who had COVID-19 might have an increased risk for developing neurodegenerative diseases, such as Parkinson’s disease, researchers in Australia found.

Moreover, the researchers have offered a possible treatment to reduce the  COVID-induced neuroinflammation.

COVID-19 activates an inflammatory response in the brain that is similar to Parkinson’s disease, contributing to the development of neurodegenerative diseases, particularly in people who are pre-disposed to the disease.

“If someone is already pre-disposed to Parkinson’s, having COVID-19 could be like pouring more fuel on that ‘fire’ in the brain,” Trent Woodruff, PhD, said in a press release.

Woodruff is last author of the study, “SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through spike protein,” that was published recently in the journal Molecular Psychiatry.

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Inflammation in the brain is a hallmark of neurodegenerative disorders such as Parkinson’s disease. Several stimuli in the central nervous system, such as pathogens, injury, or protein aggregates can activate the immune cells in the brain, leading to innate immune responses and inflammation.

SARS-CoV-2 infections were associated with neurological complications in up to 85% of the patients, from those who were asymptomatic to those with severe COVID-19. These included headache, dizziness, seizure, cerebrovascular events, and gait difficulties, among others. Psychiatric symptoms also were observed in COVID-19 patients.

Now, a research team at the University of Queensland studied “effect of the virus on the brain’s immune cells, ‘microglia’ which are the key cells involved in the progression of brain diseases like Parkinson’s and Alzheimer’s,” Woodruff said.

They found that in a preclinical mouse model, infection by SARS-CoV-2 induced the activation of microglia and an increase of inflammation in the brain.

‘Angry’ cells

When researchers “grew human microglia in the laboratory and infected the cells with SARS-CoV-2”, they found that the “cells effectively became ‘angry’, activating the same pathway that Parkinson’s and Alzheimer’s proteins can activate, the inflammasomes,” Woodruff said. Inflammasomes are proteins of the innate immune system that activate inflammatory responses.

“Triggering the inflammasome pathway sparked a ‘fire’ in the brain, which begins a chronic and sustained process of killing off neurons,” said Albornoz Balmaceda, PhD and first author of the study. He added that “It’s kind of a silent killer, because you don’t see any outward symptoms for many years.”

These results might “explain why some people who’ve had COVID-19 are more vulnerable to developing neurological symptoms similar to Parkinson’s disease,” the team said.

The inflammation process was triggered by the spike protein of the virus, and was intensified when the cells expressed proteins linked to Parkinson’s, such as alpha-synuclein fibrils. These protein toxic clumps accumulate inside nerve cells in Parkinson’s patients.

Therefore, researchers concluded that COVID-19 could contribute to the establishment of neurodegenerative disorders, such as Parkinson’s, Alzheimer’s and other dementias, particularly in people with a predisposition to a certain disease.

Potential treatment

The study also identified a potential treatment. When mice infected with SARS-CoV-2 were treated orally with an inhibitor of the inflammasome, called MCC950, the inflammatory process was reduced in microglia. The treatment increased the survival of infected mice, from 16% in untreated mice to 33% in treated mice, although the difference was not significant.

A similar effect was observed in human microglia cells, in which MCC950 reduced the inflammatory response triggered by SARS-CoV-2 infection.

“The [inhibitor] reduced inflammation in both COVID-19-infected mice and the microglia cells from humans, suggesting a possible treatment approach to prevent neurodegeneration in the future,” said Balmaceda.

According to Woodruff, the similarity between how COVID-19 and dementia diseases affect the brain was concerning. However, their research also indicates a possible available treatment.

“Further research is needed, but this is potentially a new approach to treating a virus that could otherwise have untold long-term health ramifications,” Woodruff concluded.