Researchers have discovered that the SARS-CoV-2 spike protein persists in the brain and skull bone marrow for years after infection, potentially leading to chronic inflammation and neurodegenerative diseases.
Researchers from Helmholtz Munich and Ludwig-Maximilians-Universität (LMU) have uncovered a possible explanation for the neurological symptoms associated with Long COVID. Their study reveals that the SARS-CoV-2 spike protein can persist in the brain's protective layers (the meninges) and the skull's bone marrow for up to four years after infection. This lingering spike protein may drive chronic inflammation and heighten the risk of neurodegenerative diseases.
Led by Prof. Ali Ertürk, Director of the Institute for Intelligent Biotechnologies at Helmholtz Munich, the research also found that mRNA COVID-19 vaccines significantly reduce spike protein buildup in the brain. Despite this reduction, spike proteins that remain in the skull and meninges after infection could be targeted by new therapeutic approaches to mitigate long-term effects.
Spike Protein Accumulates in the Brain
A novel AI-powered 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 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."
Impact of Vaccination on Spike Protein Levels
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.
Challenges and Advances in Long COVID Treatment
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 healthcare systems worldwide."
Diagnosing and Treating Long COVID
"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."
Reference: "Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19" by Zhouyi Rong, Hongcheng Mai, Gregor Ebert, Saketh Kapoor, Victor G. Puelles, Jan Czogalla, Senbin Hu, Jinpeng Su, Danilo Prtvar, Inderjeet Singh, Julia Schädler, Claire Delbridge, Hanno Steinke, Hannah Frenzel, Katja Schmidt, Christian Braun, Gina Bruch, Viktoria Ruf, Mayar Ali, Kurt-Wolfram Sühs, Mojtaba Nemati, Franziska Hopfner, Selin Ulukaya, Denise Jeridi, Daniele Mistretta, Özüm Sehnaz Caliskan, Jochen Martin Wettengel, Fatma Cherif, Zeynep Ilgin Kolabas, Müge Molbay, Izabela Horvath, Shan Zhao, Natalie Krahmer, Ali Önder Yildirim, Siegfried Ussar, Jochen Herms, Tobias B. Huber, Sabina Tahirovic, Susanne M. Schwarzmaier, Nikolaus Plesnila, Günter Höglinger, Benjamin Ondruschka, Ingo Bechmann, Ulrike Protzer, Markus Elsner, Harsharan Singh Bhatia, Farida Hellal and Ali Ertürk, 29 November 2024, Cell Host & Microbe.
DOI: 10.1016/j.chom.2024.11.007
News
Cancer’s Hidden Antioxidant Shield Helps It Escape the Immune System
Blocking an antioxidant protein that tumors use to suppress immune attacks improved cancer immunotherapy responses in mice. Cancer cells can release antioxidants that interfere with the immune cells trying to kill them. Researchers have [...]
Scientists Find a Berry Compound That Helps Muscle Cells Burn Fat
Pterostilbene, a compound found naturally in some foods, affects how skeletal muscles process fats by stabilizing a protein called PPARδ and increasing its signaling activity. Pterostilbene, a natural compound found in blueberries, grapes, and [...]
Two Hidden Forces Help Build the Human Brain Before Birth
Scientists have uncovered two surprising forces that help guide how the human brain forms before birth. Before birth, the human brain is shaped in large part by an unusual class of stem cells known [...]
Researchers Uncover a Hidden Trigger Behind Chronic Inflammation
The findings offer new insights that could help guide the development of future therapies. A protein called human resistin may help flip on one of the immune system’s most powerful inflammatory switches. Researchers at [...]
Scientists Have Uncovered Previously Hidden Microbial Activity on Human Skin
The most abundant microbes on your skin may not be the ones doing most of the work. Human skin supports vast communities of bacteria, fungi, and viruses that can influence its protective barrier, immune [...]
Brazilian Tree Compounds Fight COVID-19 on Multiple Fronts
Scientists found compounds in a Brazilian tree that hit SARS-CoV-2 on multiple fronts, revealing a promising new lead in the search for COVID-19 treatments. Researchers have found that galloylquinic acids extracted from the leaves [...]
Cutting Two Amino Acids Slowed Prostate Cancer in Mice
A newly identified link between amino acid metabolism and cholesterol production may help prostate tumors adapt to hormone therapy. Prostate cancer can find ways around treatments designed to deprive tumors of the hormones they [...]
Largest-Ever Physics Survey Raises New Doubts About Our Model of the Universe
Physicists around the world remain deeply divided on key mysteries of the universe, from dark matter to quantum gravity. The standard cosmological model failed to gain majority support, and no leading theory dominated the [...]
Scientists Just Overturned a 100-Year-Old Belief About Bacteria in the Lungs
New findings raise questions about the role of microbes living in the lungs. More than 35 trillion bacteria live throughout the human body, forming microbiomes in the gut, mouth, lungs, skin, and urogenital tract. [...]
GHCE Concept
From the preface of the book Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artificial Intelligence, Edited by Frank Boehm: Since the publication of my first book (Nanomedical Device and Systems [...]
Novartis, Ionis drug failure spurs questions
Pelacarsen didn’t protect heart health despite lowering levels of a protein particle, “Lp(a),” in a large clinical trial — a result with important implications for cardiovascular drug research. Dive Brief: An RNA drug from [...]
New injectable treatment helps the brain rebuild after stroke
Biomedical engineers at Duke University have created an injectable biomaterial that may help the brain recover from damage left behind by an ischemic stroke. In experiments with mice, the material transformed the cavity created [...]
Scientists Discover a Hidden “Immune Organ” Inside the Skull
Researchers discovered lymph node-like immune hubs inside skull bone marrow that appear to act as rapid-response centers for the brain. For decades, the brain was thought to operate largely apart from the immune system. [...]
Engineered tRNAs and lipid nanoparticles target nonsense mutation cystic fibrosis
Researchers have developed a potential new approach for treating a form of cystic fibrosis caused by so-called nonsense mutations, combining chemically modified transfer RNAs with lipid nanoparticles designed to deliver the therapy directly to [...]
New pancreatic cancer drug carries a $39,800 monthly list price
A groundbreaking treatment for one of the most common forms of pancreatic cancer has been approved in pill form by the FDA. Revolution Medicines’ oral tablet daraxonrasib, branded as Rasonque, reduced the risk of [...]
Researchers Have Discovered a New Way To Reduce Chronic Nerve Pain
A cancer-linked protein called BRAF may help drive chronic nerve pain, and existing cancer drugs targeting it reduced pain sensitivity in preclinical models. Chronic nerve pain can persist long after an injury and often [...]
