Researchers discover underlying cause of long COVID brain fog

A team of scientists from Trinity College Dublin and investigators from FutureNeuro have announced a major discovery of profound importance to our understanding of brain fog and cognitive decline seen in some long COVID patients. The work appears in Natural neuroscience.

In the months following the emergence of the novel coronavirus SARS-CoV2 in late 2019, a patient-reported syndrome called long COVID began to emerge as a lasting manifestation of acute infection.

To date, long COVID has up to 200 reported symptoms, but in general, patients report persistent symptoms such as fatigue, shortness of breath, memory and thinking problems, and joint/muscle pain. Although the vast majority of people suffering from COVID-19 make a full recovery, any of these symptoms that persist more than 12 weeks after infection may be considered long COVID.

Long COVID has now become a major public health problem since the outbreak of the pandemic in 2020. Although incidence rates internationally vary, it is estimated to affect up to 10% of infected patients by the SARS-CoV2 virus. Among these long COVID patients, just under 50% report some form of persistent neurological effect such as cognitive decline, fatigue, and brain fog.

Today, findings reported by the Trinity team showed that there was a disruption in the integrity of blood vessels in the brains of patients suffering from long COVID and brain fog. This “leaky” of blood vessels made it possible to objectively distinguish patients with brain fog and cognitive decline versus patients with long COVID but no brain fog.

The team led by scientists from the Smurfit Institute of Genetics in Trinity’s School of Genetics and Microbiology and neurologists from the School of Medicine also discovered a new form of MRI that shows how long COVID can affect the delicate network of blood vessels in the human brain.

“For the first time, we were able to show that leaky blood vessels in the human brain, in tandem with an overactive immune system, may be the main drivers of brain fog associated with long COVID. This is of critical importance, because understanding the underlying causes of these conditions will allow us to develop targeted therapies for patients in the future,” said Professor Matthew Campbell, Professor of Genetics and Head of Genetics at Trinity, and Principal Investigator at FutureNeuro.

This project was initiated at the height of the pandemic in 2020 and involved the recruitment of patients suffering from the effects of long COVID as well as inpatients at St James Hospital.

“Undertaking this complex clinical research study at a time of national crisis and when our hospital system was under great pressure is a testament to the skill and resources of our trainees and medical staff. The findings will now likely change the landscape of how we understand and treat post-viral neurological conditions. “It also confirms that the neurological symptoms of long COVID are measurable with real and demonstrable metabolic and vascular changes in the brain,” said Professor Colin Doherty, Professor of Neurology and Director of Trinity’s School of Medicine, and researcher. principal at FutureNeuro.

Beyond COVID-19

In recent years, it has become clear that many neurological conditions such as multiple sclerosis (MS) likely have a viral infection as the precipitating event of the pathology. However, proving this direct link has always been a challenge.

Professor Campbell added: “Here, the Trinity team was able to prove that every patient who developed long COVID had been diagnosed with SARS-CoV2 infection, as Ireland required every documented case to be diagnosed at using more precise PCR-based methods. The concept that many other viral infections leading to post-viral syndromes could result in leaky blood vessels in the brain is a potential game-changer and is under active investigation by the team.

Dr Chris Greene, postdoctoral researcher and first author of the study, added: “Our results have now paved the way for further studies examining the molecular events that lead to post-viral fatigue and brain fog. play out many disparate types of viral infection and we are now close to understanding how and why they cause neurological dysfunction in patients.