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Long COVID: Helmholtz Munich researchers identify possible cause of brain effects

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Researchers from  Helmholtz Munich and Ludwig-Maximilians-Universität (LMU) have identified a mechanism that may explain the neurological symptoms of Long COVID. The study shows that the SARS-CoV-2 spike protein remains in the protective layers of the brain, the meninges, and in the bone marrow of the skull for up to four years after infection.

This persistent presence of the spike protein could trigger chronic inflammation in those affected and increase the risk of neurodegenerative diseases. The team, led by Prof. Ali Ertürk, Director of the Institute for Intelligent Biotechnologies at Helmholtz Munich, also found that mRNA COVID-19 vaccines significantly reduce the accumulation of the spike protein in the brain.

The novel AI-based imaging technique developed by Ertürk's team provides new insights into how the SARS-CoV-2 spike protein affects the brain. The method makes organs and tissue samples transparent, enabling the three-dimensional visualization of cell structures, metabolic products and, in this case, viral proteins. Using this technology, the researchers were able to uncover a previously undetectable deposition of the spike protein in tissue samples from humans with COVID-19 and mice.

The study, published in the journal Cell Host & Microbe, showed significantly increased concentrations of the spike protein in the bone marrow of the skull and in the meninges, even years after infection. The spike protein binds to so-called ACE2 receptors, which are particularly common in these regions.

“This could make these tissues particularly susceptible to the long-term accumulation of the spike protein,” explains Dr. Zhouyi Rong, first author of the publication. According to Ertürk, the data also suggest that the persistence of spike protein at the borders of the brain could contribute to the long-term neurological effects of COVID-19 and Long COVID. These include accelerated brain ageing, which could mean the loss of five to ten years of healthy brain function for those affected.

Ertürk's team discovered that the mRNA COVID-19 vaccine from BioNTech/Pfizer significantly reduces the accumulation of spike protein in the brain. Mice vaccinated with the mRNA vaccine showed lower spike protein levels in both brain tissue and bone marrow of the skull compared to unvaccinated mice. However, the reduction was only about 50%, meaning that residual spike protein still poses a toxic risk to the brain.

The spike protein remaining in the skull and meninges after infection represents a new therapeutic target to fully manage long-term exposure to SARS-CoV-2 infections. Further studies are needed to investigate the relevance of the results for patients with long-term COVID. However, the results open up new possibilities for diagnosing and treating the long-term neurological effects of COVID-19.

Worldwide, 50 to 60 percent of the population has been infected with COVID-19. About five to ten percent, around 400 million people, suffer from Long COVID.

Click here for the original publication (DOI: 10.1016/j.chom.2024.11.007).

 

 


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