Protein accumulation associated with long-COVID neurological symptoms

Spike protein accumulates in the brain

A novel AI-assisted imaging technique developed by Prof. Ali 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 and enables three-dimensional visualization of cell structures, metabolites and, in this case, viral proteins. Using this technology, researchers discovered previously undetectable distributions of spike protein in tissue samples from COVID-19 patients and mice.

The study, published in the journal Cell Host & Microbe, found significantly elevated levels of spike protein in the bone marrow and meninges of the skull, 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 vulnerable to long-term accumulation of spike protein,” explains Dr. Zhouyi Rong, the first author of the study. Ertürk adds: “Our data also suggests that persistent spike protein at the brain borders may contribute to the long-term neurological effects of COVID-19 and Long COVID.” These include accelerated brain aging, which may occur in affected individuals a loss of healthy brain function lasting five to ten years.”

Vaccines reduce spike protein buildup and brain inflammation

Ertürk’s team discovered that BioNTech/Pfizer’s mRNA COVID-19 vaccine significantly reduced the accumulation of spike protein in the brain. Other mRNA vaccines or types of vaccines, such as vector- or protein-based vaccines, have not been studied. Mice vaccinated with the mRNA vaccine showed lower levels of spike protein in both brain tissue and the bone marrow of the skull compared to unvaccinated mice. However, the reduction was only about 50%, leaving residual spike proteins that continue to pose a toxic risk to the brain.

“This reduction is an important step,” says Prof. Ertürk. “Although our results come from mouse models and are only partially applicable to humans, they point to the need for additional therapies and interventions to fully address the long-term burden of SARS-CoV-2 infections.” Additionally, additional studies are needed to assess the relevance of these results for Long COVID patients.

Long COVID: A social and medical challenge

Globally, 50 to 60 percent of the population is infected with COVID-19, with five to ten percent suffering from long COVID. This equates to approximately 400 million people who may carry significant amounts of spike protein. “This is not just an individual health problem, it is a societal challenge,” says Prof. Ertürk. “Our study shows that mRNA vaccines significantly reduce the risk of long-term neurological consequences and provide crucial protection. However, infections can still occur after vaccination, resulting in persistent spike proteins in the body. These can lead to chronic brain inflammation and an increased risk of stroke and other brain injuries, which could have significant implications for global public health and health systems worldwide.”

Advances in diagnosis and treatment

“Our findings open up new possibilities for diagnosing and treating the long-term neurological effects of COVID-19,” says Ertürk. Unlike brain tissue, the bone marrow and meninges of the skull—areas prone to the accumulation of spike proteins—are more accessible for medical examination. Combined with protein panels – tests that detect specific proteins in tissue samples – this could allow the identification of spike proteins or inflammatory markers in blood plasma or cerebrospinal fluid. “Such markers are crucial for the early detection of neurological complications related to COVID-19,” explains Ertürk. “In addition, the characterization of these proteins may support the development of targeted therapies and biomarkers to better treat or even prevent neurological impairments caused by COVID-19.”

Leading virologist from Helmholtz Munich and the Technical University of Munich, Prof. Ulrike Protzer, emphasizes the broader impact of the study and adds: “Given the ongoing global impact of COVID-19 and the increasing focus on long-term effects, this study sheds light on the matter .” Brain invasion pathways and unexpected long-term host involvement is timely. These critical findings are not only scientifically important, but also of great social interest.”

Reference: Rong Z, Mai H, Ebert G, et al. The persistence of spike protein at the cranioskeletal-brain axis may contribute to the neurological consequences of COVID-19. Cell host microbe. 2024. doi: 10.1016/j.chom.2024.11.007

This article is republished from the following materials. Note: Material may have been edited for length and content. For further information, please contact the source provided. Our guidelines for publishing press releases can be found here Here.