April 13, 2023 – If you or someone you understand is affected by “brain fog” after contracting COVID-19, scientists now have a possible explanation – and it might not be much consolation.
Researchers in Germany found that a part of the virus, the spike protein, stays within the brain long after the virus has been eliminated.
These researchers discovered the virus's spike protein within the brain tissue of animals and humans after death. The finding suggests that these virus fragments accumulate, stick around, and trigger inflammation that results in long-lasting COVID symptoms.
About 15% of COVID patients still suffer from long-term effects of the infection despite their recovery, said lead study creator Ali Ertürk, PhD, director of the Institute for Tissue Engineering and Regenerative Medicine on the Helmholtz Center Munich in Germany.
Reported neurological problems include brain fog, lack of brain tissue, a decrease in pondering ability and memory problems, he said.
“These symptoms clearly indicate damage and long-term changes caused by SARS-CoV-2 in the brain, the exact molecular mechanisms of which are still poorly understood,” said Ertürk.
The researchers also suggest a way for the spike protein to enter the brain Preprint report published online ahead of peer review on 5 April bioRxiv.
The spike protein is transported through the circulating blood and may remain in small openings within the bone marrow of the skull, called niches. It can be present in the meningesthin layers of cells that act as a buffer between the skull and the brain. From there, based on one theory, the spike protein uses channels to penetrate into the brain itself.
The hope is that researchers can develop treatments that block a number of steps on this process and help people avoid long-term COVID brain problems.
“Very worrying”
“This is a very concerning report that literally detects the SARS-CoV-2 spike protein in the craniocerebral axis in postmortem individuals,” said Eric Topol MD, director of the Scripps Research Translational Institute in La Jolla, California, and editor in chief of Medscape, WebMD's sister site for healthcare professionals.
That the spike protein accumulates in structures just outside the brain and causes persistent inflammation seems plausible to Topol. The accumulation of spike proteins would trigger an immune response from this area of interest reservoir of immune cells, causing the inflammation related to long COVID and the symptoms equivalent to brain fog, he said.
Problems with pondering and memory after a COVID infection are relatively common. A research team found 22% of people with Long COVID On average, 43 published studies specifically reported this problem. Even individuals who had mild COVID illness can later develop brain fog, Ertürk and colleagues note.
So why do researchers blame the spike protein and never all the COVID virus? In the study, they found SARS-CoV-2 virus RNA in some people after they died and never in others, suggesting the virus doesn't need to be present to cause brain fog. They also injected the spike protein directly into the brains of mice and showed that it could cause cells to die.
The researchers were also unable to detect any SARS-CoV-2 virus within the brain parenchyma – the functional tissue of the brain, which consists of nerve cells and non-nervous (so-called glial) cells – but they were in a position to detect the spike protein.
Surprising findings
The researchers were surprised to seek out spike protein within the skull niches of people that survived COVID and later died from one other cause. Ertürk, lead creator and doctoral student Zhouyi Rong and their colleagues found spike protein in 10 of 34 skulls of people that died from causes apart from COVID in 2021 and 2022.
They also found that COVID can alter the actions of proteins in and across the brain. Some of those proteins are linked to Parkinson's and Alzheimer's, but have never been linked to the virus until now.
Another unexpected finding was how similar the outcomes were in mice and humans. There was a “remarkable similarity in the distribution of the viral spike protein and the dysregulated proteins identified in the mouse and human samples,” Ertürk said.
Future treatments?
Testing for protein changes within the skull or meninges could be invasive, but feasible in comparison with taking samples of the brain parenchyma. Even less invasive could be testing blood samples for altered proteins, which could discover people who find themselves most vulnerable to developing brain complications after COVID.
To achieve this goal, further brain research is required. “To develop treatment strategies for these neurological symptoms, in-depth knowledge of the molecules that are disrupted by the virus in brain tissue is required,” said Ertürk.