‘Game Changing’ Study Finds Cause of Long Covid Brain Fog

By Pat Anson, PNN Editor

Inflamed and leaky blood vessels in the human brain appear to be the cause of brain fog and other cognitive issues in patients with Long Covid, according to a groundbreaking study by a team of Irish researchers.

The discovery that a viral infection may cause cognitive decline could help explain why memory loss, confusion and trouble concentrating is common in patients with other chronic illnesses, such as fibromyalgia, multiple sclerosis and chronic fatigue syndrome (ME/CFS).

Scientists at Trinity College Dublin and FutureNeuro used a specialized MRI to compare the brains of Long Covid patients with brain fog to those without brain fog.

The MRI images show how Long Covid can affect the brain’s delicate network of blood vessels. Patients with brain fog (right column) have significantly more inflammation and blood vessel leakage than those without brain fog (left column).

Patients with brain fog also had more elevated levels of glial fibrillary acidic protein (GFAP) in their blood, which is a sign of cerebrovascular damage often found in patients with repetitive head trauma.

The images and findings are published in the journal Nature Neuroscience.

“For the first time, we have been able to show that leaky blood vessels in the human brain, in tandem with a hyperactive immune system, may be the key drivers of brain fog associated with Long COVID,” said lead author Matthew Campbell, PhD, a Professor in Genetics and Head of Genetics at Trinity College, and Principal Investigator at FutureNeuro. 

“The concept that many other viral infections that lead to post-viral syndromes might drive blood vessel leakage in the brain is potentially game changing and is under active investigation by the team.” 

NATURE NEUROSCIENCE

About 10% of the people infected with the SARS-CoV2 virus develop Long Covid, a broad range of conditions that causes fatigue, shortness of breath, and muscle and joint pain. About half of Long Covid patients also report brain fog or some lingering neurological issue. 

“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 co-author Colin Doherty, Professor of Neurology and Head of the School of Medicine at Trinity, and Principal Investigator at FutureNeuro. 

In recent years, research has found that multiple sclerosis, lupus and other autoimmune conditions are triggered by the Epstein-Barr virus. The exact mechanism is unclear and proving there is a direct link between viral infections and brain fog has been challenging – until now.   

“Our findings have now set the stage for further studies examining the molecular events that lead to post-viral fatigue and brain fog. Without doubt, similar mechanisms are at play across many disparate types of viral infection and we are now tantalisingly close to understanding how and why they cause neurological dysfunction in patients,” said first author Chris Greene, PhD, a research fellow in the School of Genetics and Microbiology at Trinity.

The study was funded by Science Foundation Ireland, the European Research Council and FutureNeuro, a research center for chronic and rare neurological diseases.

12 Most Common Symptoms of Long Covid

By Pat Anson, PNN Editor

Since the first cases started appearing in 2020, medical experts have been baffled by Long Covid, a poorly understood disorder that causes chronic fatigue, insomnia, brain fog and dozens of other symptoms long after the initial infection with COVID-19.

The symptoms vary so much from person to person that identifying the cause is difficult. Is it Long Covid? Fibromyalgia? Chronic fatigue syndrome? Lyme disease? Or just a bad case of the flu?   

A new study led by the National Institutes of Health's RECOVER Initiative has identified the 12 most common symptoms of Long Covid, with the goal of creating a working definition of the condition to help make it easier to diagnose and treat.

"This study is an important step toward defining Long Covid beyond any one individual symptom," said lead author Leora Horwitz, MD, director of the Center for Healthcare Innovation and Delivery Science at NYU Langone Health. "This definition — which may evolve over time — will serve as a critical foundation for scientific discovery and treatment design."

Horwitz and her colleagues studied survey data from 9,764 adult volunteers from across the country. Nearly 90% had been infected with Covid. Some made complete recoveries, while others had symptoms of Long Covid – known technically as postacute sequelae of SARS-CoV-2 infection (PASC). About 23% of participants with a prior Covid infection met the working definition for Long Covid.

The study findings, published in JAMA, examined 37 symptoms across multiple body areas and organs. Researchers then applied statistical analysis to identify the 12 symptoms that someone with Long Covid is most likely to have: post-exertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, heart palpitations, issues with sexual desire, loss of smell or taste, thirst, chronic cough, chest pain, and abnormal movements.

By assigning points to each of the 12 symptoms, researchers gave each participant a PASC score based on their combination of symptoms. Some symptoms appeared at higher rates than others, with malaise and fatigue being the most prominent, occurring in nearly 90% of cases.

Frequency of Long Covid Symptoms

SOURCE: JAMA

"Now that we're able to identify people with Long Covid, we can begin doing more in-depth studies to understand the mechanisms at play," said coauthor Andrea Foulkes, ScD, Principal Investigator of the RECOVER Data Resource Core. "These findings set the stage for identifying effective treatment strategies for people with Long Covid — understanding the biological underpinnings is going to be critical to that endeavor."

The researchers found that Long Covid was more common and severe in participants who were infected before the Omicron strain emerged in late 2021. People who were unvaccinated and those with multiple Covid infections were also more likely to have severe symptoms.

Researchers identified four subgroups of patients with different clusters of symptoms. Some clusters spanned multiple organs, such as the heart, lung and brain, suggesting that a body-wide reaction to the virus may occur in some people with Long Covid.

As of May 2023, more than 100 million Americans have been infected with COVID-19, with experts estimating that about 6 percent of those infected with the virus continue to experience Long Covid symptoms.