Long COVID: Persistent spike proteins accumulate in the brain

Long COVID is the lingering aftermath of infection by the SARS-CoV-2 virus. It is estimated that millions of adults, in the U.S. alone, have suffered from this condition.

What is it about this virus that takes such a toll on the human body and, more specifically, the brain?

A revolutionary exploration of long COVID

A team of experts from Helmholtz Munich and Ludwig-Maximilians-Universität (LMU) explored this medical mystery in depth. They unearthed an intriguing factor – the notorious SARS-CoV-2 spike protein may be guilty of causing persistent brain effects.

These lingering proteins nestle within our brain’s protective membranes – the meninges – and the bone marrow within our skulls for up to four years post-infection.

Just like a squatter in an abandoned house, these proteins become unwelcome residents, causing chronic inflammation and amplifying the risk of neurodegenerative diseases.

The research team also pointed out promising news. It seems that mRNA COVID-19 vaccines reduce the accumulation of this protein in the brain.

Despite this, the stubborn persistence of spike proteins offers a potential hotspot for future therapeutic strategies.

The impact of the spike protein

So, how does this dreaded spike protein invade our brain? An advanced, AI-powered, imaging technique forms the backbone of the researchers’ answer to this question.

The breakthrough method transforms organs and tissue samples into transparent structures. It’s like having a clear blueprint of a complex building, that allows a three-dimensional view of cellular structures, metabolites and, in this case, viral proteins.

The research revealed unexpected deposits of the spike protein in tissue samples from patients and mice.

Strikingly, there was an influx of this protein in the bone marrow of the skull and meninges, even years after infection.

These proteins attach themselves to ACE2 receptors, which are particularly prevalent in these regions.

“This may make these tissues especially vulnerable to the long-term accumulation of spike protein,” noted study lead author Dr. Zhouyi Rong.

Spike protein and long COVID impacts

Study co-author Professor Ertürk is a researcher at the Institute for Tissue Engineering and Regenerative Medicine (iTERM), at Helmholtz Munich.

“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,” said Professor Ertürk.

“This includes accelerated brain aging, potentially leading to a loss of five to ten years of healthy brain function in affected individuals.”

Vaccines and their role

We know that vaccines offer a protective shield against the virus. But how do they stand against this protein accumulation?

The research team discovered that the BioNTech/Pfizer mRNA COVID-19 vaccine puts a significant hurdle in the pathway of spike protein accumulation in the brain.

The hitch? Even though there was a reduction in the spike protein levels, about 50% of it still remained. These leftovers continue to pose a toxic risk to the brain. Nevertheless, the team remains optimistic.

“This reduction is an important step. 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,” said Professor Ertürk.

Societal challenge of long COVID

Long COVID isn’t only a personal health issue affecting individuals. About 50 to 60% of the world’s population has battled with COVID-19, and a significant chunk have experienced long COVID – adding up to roughly 400 million individuals.

“This is not just an individual health issue – it is a societal challenge. Our study shows that mRNA vaccines significantly reduce the risk of long-term neurological consequences and offer crucial protection,” said Professor Ertürk.

“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.”

Advancements in diagnosis and treatment

The silver lining to this research is that it points to promising new avenues for diagnosing and treating these long-term neurological impacts of COVID-19.

Unlike brain tissue, the areas prone to spike protein accumulation – the bone marrow of the skull, along with the meninges – are easier to access for medical examinations.

Combined with protein panels – tests designed to detect specific proteins in tissue samples – this could allow for the early detection 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,” said Professor Ertürk.

“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.”

The full study was published in the journal Cell Host & Microbe.

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