While COVID-19 primarily affects the lungs, about 30% of people with the disease suffer from brain-related issues like memory loss, difficulty concentrating, sensory distortion, and severe headaches that can linger months after infection. Researchers believe these symptoms result from entry of the virus into the central nervous system, but how the virus triggers these symptoms in the brain has been unclear. Now, researchers in Australia and Luxembourg have discovered what may be causing brain fog and other chronic cognitive symptoms.*

What the researchers did

A research team led by Melbourne’s Swinburne University of Technology and La Trobe University noted that some of Long COVID’s neurological symptoms are much like the early stages of brain diseases like Alzheimer’s and Parkinson’s. The team acted on the theory that some of Long COVID’s neurological symptoms may be due to amyloids (clumps of abnormal or mis-folded proteins) in the brain.

• Certain proteins from the SARS-CoV-2 virus that have no apparent role in virus replication, and so may be free to disrupt immune response, were chosen for study.
• These protein fragments, called disordered or unstructured proteins, are able to take on different forms, and were thus deemed “good candidates” for amyloid development.
• The proteins, also called ‘open reading frames’ (ORFs) were screened for their amyloid-forming potential using advanced technology.

What they found

The study findings, published in the journal Nature Communications, identified two proteins (ORF6 and ORF10) that each rapidly assembled into amyloid clumps in the brain. The amyloids “are highly toxic to brain cells,” even at very low concentrations, and were found to look similar to the amyloids in Alzheimer’s and Parkinson’s disease.

What it means

The researchers say that, in addition to the two protein fragments with high amyloid-forming potential that were found, there could very well be others in the central nervous system of COVID-19 patients, since the virus has been proven to enter the brain. Because these amyloid formations are both toxic and resistant to enzymatic breakdown, they could persist after infection and help to explain common Long COVID-related cognitive complaints. 

It’s uncertain whether the persistent neurological symptoms in Long COVID could lead to the progressive brain deterioration seen in diseases like Alzheimer’s, say the researchers. “Given the typically slow progress of neurodegenerative disease if such a phenomenon exists, it will most probably take some time to become evident epidemiologically.”

Meanwhile, study author Mirren Charnley, Ph.D., a postdoctoral researcher at Swinburne, is hopeful about the study’s potential for helping to treat Long COVID-related brain symptoms. “If further studies are able to prove that the formation of these amyloids is causing Long-COVID, then anti-amyloid drugs developed to treat Alzheimer’s might be used to treat some of the neurological symptoms of Long-COVID.”

*Swinburne University of Technology. (2022, July 4). Study reveals possible cause of long COVID ‘brain fog.’ https://www.swinburne.edu.au/news/2022/07/study-reveals-possible-cause-of-long-covid-brain-fog