Researchers discover how SARS-CoV-2 impacts the brain, and aim to reverse and prevent long COVID

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Many of us have experienced the symptoms of long COVID – brain fog, extreme tiredness and fatigue, headache, anxiety, and sleep problems are all part of the slump that can be felt after contracting the virus.  

But now, researchers at the Queensland Brain Institute are aiming to reverse this process, or prevent it altogether thanks to a significant new breakthrough.  

Brain cells must remain individual units to function correctly and to communicate with each other, and for more than 10 years, Group leader Professor Massimo Hilliard has been interested in understanding this process during brain development and upon injury.  

The emergence of COVID-19 in 2020 allowed his team to discover that the COVID virus causes brain cells to lose their individuality and fuse with each other, which makes them become dysfunctional and potentially cause neurological symptoms.   

“Our results showed that one of the consequences of neuronal fusion is the synchronization of their electrical activities, and another is their complete silencing,” Professor Hilliard said.  

“While we currently cannot directly connect the neuropathology of neuronal fusion with specific symptoms of long COVID, it is likely that neuronal fusion can explain a variety of them based on which part of the brain is affected and the extent of the neurons involved.    

“For example, synchronized bursts from a sufficient number of neurons can initiate seizures, and a higher risk of epilepsy and seizures are commonly observed in long COVID complications.”   

Professor Hilliard said the finding is significant and he believes it could “revolutionise” the way we understand and treat neurological illnesses.  

“Our discovery of a novel neuropathological mechanism caused by viruses and their surface molecules called fusogens holds the promise to revolutionise the way we understand and potentially develop treatments for these pathogens and their molecules in the brain,” he said.  

Dr Ramon Martinez-Marmol, a postdoctoral fellow in the Hilliard lab and the first author of the work, focused on studying the SARS-CoV-2 virus allowing the team to make this breakthrough.  

Dr Martinez-Marmol said that identifying the impact of COVID and the reversibility of long COVID became even more a focus of his research after witnessing its effects on family members who had fallen ill with the virus.  

“Several members of my family suffered anosmia post-COVID, that has not completely recovered,” he said.  

“As a consequence of our work, we were contacted by many patients of long COVID, who have shared their experiences and problems.”  

The goal is to ultimately prevent these symptoms in humans or reverse the effects in those currently living with the condition.  

But some evidence suggests the process could also be irreversible. The team has further  planned to determine whether this is true.  

“Our results suggest that brain cell fusion might be an irreversible process; however, we have not directly tested this aspect and cannot yet provide a definitive answer,” Dr Martinez-Marmol said.  

“Independently of the nature of the process – whether it is spontaneously reversible or not – we aim to identify ways to induce its reversibility as well as to prevent it from happening in the first place.”  

“Many viruses can affect the brain, and several of them are fusogenic. We are also interested in expanding our discoveries to other viruses of concern”. 

The challenge the team faces is the fact that brain cell fusion cannot yet be detected in human brains.  

However, the Hilliard team has begun work with Professor Lars Ittner at Macquarie University to make this a reality.  

“We haven’t yet studied the brain of patients with long COVID; however, based on this new knowledge we generated, we believe it is now achievable to detect brain cell fusion in the post-mortem patients’ brain and it might eventually become possible to detect it in the live patients,” Professor Hilliard said.  

“These are our current lines of research that we are pursuing in collaboration with Professor Lars Ittner at Macquarie University.”  

Along with Professor Ittner, the team’s success has also been the result of fruitful collaboration with several other partners.  

These include Associate Professor Yazi Ke from the Dementia Research Centre at Macquarie University, Associate Professor Giuseppe Balistreri at the University of Helsinki in Finland, Professor Fred Meunier at QBI, and Associate Professor Kirsty Short at the School of Chemistry and Molecular Biosciences at UQ.    

This discovery was featured in Science Advances.