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
NanoMedical Brain/Cloud Interface – Explorations and Implications. A new book from Frank Boehm
New book from Frank Boehm, NanoappsMedical Inc Founder: This book explores the future hypothetical possibility that the cerebral cortex of the human brain might be seamlessly, safely, and securely connected with the Cloud via [...]
How lipid nanoparticles carrying vaccines release their cargo
A study from FAU has shown that lipid nanoparticles restructure their membrane significantly after being absorbed into a cell and ending up in an acidic environment. Vaccines and other medicines are often packed in [...]
New book from NanoappsMedical Inc – Molecular Manufacturing: The Future of Nanomedicine
This book explores the revolutionary potential of atomically precise manufacturing technologies to transform global healthcare, as well as practically every other sector across society. This forward-thinking volume examines how envisaged Factory@Home systems might enable the cost-effective [...]
A Virus Designed in the Lab Could Help Defeat Antibiotic Resistance
Scientists can now design bacteria-killing viruses from DNA, opening a faster path to fighting superbugs. Bacteriophages have been used as treatments for bacterial infections for more than a century. Interest in these viruses is rising [...]
Sleep Deprivation Triggers a Strange Brain Cleanup
When you don’t sleep enough, your brain may clean itself at the exact moment you need it to think. Most people recognize the sensation. After a night of inadequate sleep, staying focused becomes harder [...]
Lab-grown corticospinal neurons offer new models for ALS and spinal injuries
Researchers have developed a way to grow a highly specialized subset of brain nerve cells that are involved in motor neuron disease and damaged in spinal injuries. Their study, published today in eLife as the final [...]
Urgent warning over deadly ‘brain swelling’ virus amid fears it could spread globally
Airports across Asia have been put on high alert after India confirmed two cases of the deadly Nipah virus in the state of West Bengal over the past month. Thailand, Nepal and Vietnam are among the [...]
This Vaccine Stops Bird Flu Before It Reaches the Lungs
A new nasal spray vaccine could stop bird flu at the door — blocking infection, reducing spread, and helping head off the next pandemic. Since first appearing in the United States in 2014, H5N1 [...]
These two viruses may become the next public health threats, scientists say
Two emerging pathogens with animal origins—influenza D virus and canine coronavirus—have so far been quietly flying under the radar, but researchers warn conditions are ripe for the viruses to spread more widely among humans. [...]
COVID-19 viral fragments shown to target and kill specific immune cells
COVID-19 viral fragments shown to target and kill specific immune cells in UCLA-led study Clues about extreme cases and omicron’s effects come from a cross-disciplinary international research team New research shows that after the [...]
Smaller Than a Grain of Salt: Engineers Create the World’s Tiniest Wireless Brain Implant
A salt-grain-sized neural implant can record and transmit brain activity wirelessly for extended periods. Researchers at Cornell University, working with collaborators, have created an extremely small neural implant that can sit on a grain of [...]
Scientists Develop a New Way To See Inside the Human Body Using 3D Color Imaging
A newly developed imaging method blends ultrasound and photoacoustics to capture both tissue structure and blood-vessel function in 3D. By blending two powerful imaging methods, researchers from Caltech and USC have developed a new way to [...]
Brain waves could help paralyzed patients move again
People with spinal cord injuries often lose the ability to move their arms or legs. In many cases, the nerves in the limbs remain healthy, and the brain continues to function normally. The loss of [...]
Scientists Discover a New “Cleanup Hub” Inside the Human Brain
A newly identified lymphatic drainage pathway along the middle meningeal artery reveals how the human brain clears waste. How does the brain clear away waste? This task is handled by the brain’s lymphatic drainage [...]
New Drug Slashes Dangerous Blood Fats by Nearly 40% in First Human Trial
Scientists have found a way to fine-tune a central fat-control pathway in the liver, reducing harmful blood triglycerides while preserving beneficial cholesterol functions. When we eat, the body turns surplus calories into molecules called [...]
A Simple Brain Scan May Help Restore Movement After Paralysis
A brain cap and smart algorithms may one day help paralyzed patients turn thought into movement—no surgery required. People with spinal cord injuries often experience partial or complete loss of movement in their arms [...]
