The SARS-CoV-2 virus may increase the likelihood of the brain degeneration found in Parkinson’s disease, according to a study in mice.
COVID-19 patients commonly report symptoms such as brain fog, headaches, and insomnia, complications that are not new after a viral infection, the researchers said. It took nearly a decade for patients to develop the neurological disease known as ”post-encephalic parkinsonism” after the 1918 influenza pandemic, they said.
The study, published in the journal Movement Disorders, found that the SARS-CoV-2 virus could raise the brain’s susceptibility to a toxin that causes the death of nerve cells seen in Parkinson’s disease.
”Parkinson’s is a rare disease that affects 2 percent of the population above 55 years, so the increase in risk is not necessarily a cause for panic,” said study first author Richard Smeyne, from Thomas Jefferson University, US.
”But understanding how coronavirus impacts the brain can help us prepare for the long-term consequences of this pandemic,” Smeyne said.
The study expands on prior findings from the Smeyne lab indicating that viruses can increase the susceptibility of brain cells or neurons to damage or death.
In that study, the researchers discovered that mice exposed to the H1N1 influenza strain that caused the 2009 flu pandemic were more vulnerable to MPTP.
MPTP is a toxin known to cause some of the characteristic symptoms of Parkinson’s disease, most notably the loss of neurons that express the chemical dopamine and increased inflammation in the basal ganglia, a brain region that is crucial for movement.
The latest study employed mice that were genetically altered to express the human ACE-2 receptor, which the SARS-CoV-2 virus utilizes to get access to the cells in our airways.
These mice were infected with SARS-CoV-2 and then allowed to recover, the researchers said.
The dosage used in this research corresponds to a mild COVID-19 infection in people, with around 80 percent of infected mice surviving, they said.
Thirty-eight days after the surviving mice had recovered, one group was given a modest dosage of MPTP that would not ordinarily trigger neuron loss.
The control group was given saline. The animals were sacrificed and their brains were examined two weeks later.
The researchers found that COVID-19 infection alone had no impact on dopaminergic neurons in the basal ganglia.
However, mice given a modest dosage of MPTP after recovering from infection demonstrated the classic pattern of neuron loss found in Parkinson’s disease.
This increased sensitivity following COVID-19 infection was comparable to what was reported in the influenza trial, suggesting that both viruses might cause an equal increase in the risk of developing Parkinson’s.
”We think about a ‘multi-hit’ hypothesis for Parkinson’s — the virus itself does not kill the neurons, but it does make them more susceptible to a ‘second hit’, such as a toxin or bacteria or even an underlying genetic mutation,” Smeyne explained.
Both influenza and SARS-CoV2 have been found to cause a ”cytokine storm” or an overproduction of pro-inflammatory chemicals. These chemicals can cross the blood-brain barrier and activate the brain’s immune cells – microglia.
The researchers found increased numbers of activated microglia in the basal ganglia of mice that recovered from SARS-CoV2 and received MPTP.
While the mechanism is not fully understood, they believe the increased microglia inflame the basal ganglia and cause cellular stress. This then lowers the neurons’ threshold to withstand subsequent stress.
”We were concerned about the long-term consequences of viral infection,” said Peter Schmidt, a neuroscientist from New York University in the US, who co-led the study.
The researchers are planning to determine whether vaccines can mitigate the experimental increase in Parkinson’s pathology linked to prior SARS-CoV-2 infection.
They are also testing other variants of the virus, as well as doses that correspond to milder cases in humans.
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