Summary: A new study reveals that the SARS-CoV-2 spike protein remains in brain-protective tissues and skull bone marrow for years after infection, potentially driving long COVID’s neurological symptoms. Using advanced imaging, researchers discovered elevated spike protein levels in these regions, leading to chronic brain inflammation and increased risks of neurodegenerative conditions.
mRNA COVID-19 vaccines were shown to reduce spike protein accumulation by 50%, though residual protein may still pose risks. The findings highlight the need for new therapies and early diagnostic tools to address long-term effects on brain health.
Key Facts:
- Spike protein persists in brain tissues and skull bone marrow for years post-infection.
- mRNA vaccines reduce spike protein accumulation in the brain by 50%.
- Chronic spike protein presence may accelerate brain aging and increase stroke risk.
Source: Helmholtz
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 brain’s protective layers, the meninges, and the skull’s bone marrow for up to four years after infection.
This persistent presence of the spike protein could trigger chronic inflammation in affected individuals and increase the risk of neurodegenerative diseases.
The team, led by Prof. Ali Ertürk, Director at 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.
However, the persistence of spike protein after infection in the skull and meninges offers a target for new therapeutic strategies.
Spike protein accumulates in the brain
A novel AI-powered imaging technique developed by Prof. Ertürk’s team provides new insights into how the SARS-CoV-2 spike protein affects the brain.
The method renders organs and tissue samples transparent, enabling the three-dimensional visualization of cellular structures, metabolites, and, in this case, viral proteins.
Using this technology, the researchers uncovered previously undetectable distributions of spike protein in tissue samples from COVID-19 patients and mice.
The study, published in the journal Cell Host & Microbe, revealed significantly elevated concentrations of spike protein in the skull’s bone marrow and meninges, even years after infection.
The spike protein binds to so-called ACE2 receptors, which are particularly abundant in these regions.
“This may make these tissues especially vulnerable to the long-term accumulation of spike protein,” explains Dr. Zhouyi Rong, the study’s first author.
Ertürk adds, “Our data also suggest that persistent spike protein at the brain’s borders may contribute to the long-term neurological effects of COVID-19 and long COVID. This includes accelerated brain aging, potentially leading to a loss of five to ten years of healthy brain function in affected individuals.”
Vaccines reduce spike protein accumulation and brain inflammation
The Ertürk team discovered that the BioNTech/Pfizer mRNA COVID-19 vaccine significantly reduces the accumulation of spike protein in the brain. Other mRNA vaccines or vaccine types, such as vector- or protein-based vaccines, were not investigated.
Mice vaccinated with the mRNA vaccine showed lower levels of spike protein in both brain tissue and the skull’s bone marrow compared to unvaccinated mice. However, the reduction was only around 50%, leaving residual spike protein that continues to pose a toxic risk to the brain.
“This reduction is an important step,” says Prof. Ertürk. “Our results, while derived from mouse models and only partially transferable to humans, point to the need for additional therapies and interventions to fully address the long-term burdens caused by SARS-CoV-2 infections.”
Furthermore, additional studies are needed to evaluate the relevance of these findings for long COVID patients.
Long COVID: A societal and medical challenge
Globally, 50 to 60 percent of the population has been infected with COVID-19, with five to ten percent experiencing long COVID. This sums up to approximately 400 million individuals who may carry significant amounts of spike protein.
“This is not just an individual health issue—it is a societal challenge,” says Prof. Ertürk.
“Our study shows that mRNA vaccines significantly reduce the risk of long-term neurological consequences and offer crucial protection. However, infections can still occur post-vaccination, leading to persistent spike proteins in the body.
“These can result in chronic brain inflammation and an increased risk of strokes and other brain injuries, which could have substantial implications for global public health and health care systems worldwide.”
Advances in diagnosis and treatment
“Our findings open new possibilities for diagnosing and treating the long-term neurological effects of COVID-19,” says Ertürk.
Unlike brain tissue, the skull’s bone marrow and meninges—areas prone to spike protein accumulation—are more accessible for medical examinations.
Combined with protein panels—tests designed to detect specific proteins in tissue samples—this could allow for the identification of spike proteins or inflammatory markers in blood plasma or cerebrospinal fluid.
“Such markers are critical for the early diagnosis of COVID-19-related neurological complications,” Ertürk explains.
“Additionally, characterizing these proteins may support the development of targeted therapies and biomarkers to better treat or even prevent neurological impairments caused by COVID-19.”
Highlighting the broader impact of the study, leading Helmholtz Munich and Technical University of Munich virologist Prof. Ulrike Protzer adds, “Given the ongoing global impact of COVID-19 and the increasing focus on long-term effects, this study, which sheds light on brain invasion pathways and unexpected long-term host involvement, is timely. These critical insights are not only scientifically significant but also of great interest to society.”
About this long COVID research news
Author: Verena Schulz
Source: Helmholtz
Contact: Verena Schulz – Helmholtz
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19” by Zhouyi Rong et al. Cell Host & Microbe
Abstract
Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19
SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear.
Using optical clearing and imaging, we observed the accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis of human COVID-19 patients, persisting long after viral clearance.
Further, biomarkers of neurodegeneration were elevated in the cerebrospinal fluid from long COVID patients, and proteomic analysis of human skull, meninges, and brain samples revealed dysregulated inflammatory pathways and neurodegeneration-associated changes.
Similar distribution patterns of the spike protein were observed in SARS-CoV-2-infected mice.
Injection of spike protein alone was sufficient to induce neuroinflammation, proteome changes in the skull-meninges-brain axis, anxiety-like behavior, and exacerbated outcomes in mouse models of stroke and traumatic brain injury.
Vaccination reduced but did not eliminate spike protein accumulation after infection in mice.
Our findings suggest persistent spike protein at the brain borders may contribute to lasting neurological sequelae of COVID-19.
