New research pinpoints cause of Long COVID symptoms

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By Stephen Beech via SWNS

Long COVID symptoms are caused by damage to the brain’s “control center”, the latest scanning technology has revealed.

Cambridge and Oxford University scientists discovered that damage to the brainstem is behind the long-lasting physical and psychiatric effects of severe COVID-19 infection.

Using ultra-high-resolution MRI scanners that can see the living brain in fine detail, the team was able to observe the damaging effects COVID-19 can have on grey matter.

They scanned the brains of 30 people who had been admitted to hospital with severe COVID-19 in the early stages of the pandemic before vaccines were available.

The researchers found that COVID-19 infection damages the region of the brainstem associated with breathlessness, fatigue and anxiety.

The powerful MRI scanners used in the study – known as 7-Tesla or 7T scanners – can measure inflammation in the brain.

Researchers say their findings, published in the journal Brain, will help doctors and scientists understand the long-term effects of COVID-19 on the brain and the rest of the body.

They explained that the brainstem, which connects the brain to the spinal cord, is the “control center” for many basic life functions and reflexes.

Clusters of nerve cells in the brainstem, known as nuclei, are responsible for regulating and processing essential bodily functions such as breathing, heart rate, pain and blood pressure.

First author Dr. Catarina Rua, of Cambridge University, said: “Things happening in and around the brainstem are vital for quality of life, but it had been impossible to scan the inflammation of the brainstem nuclei in living people, because of their tiny size and difficult position.

“Usually, scientists only get a good look at the brainstem during post-mortem examinations.”

Cambridge Professor James Rowe, who co-led the research, said: “The brainstem is the critical junction box between our conscious selves and what is happening in our bodies.

“The ability to see and understand how the brainstem changes in response to COVID-19 will help explain and treat the long-term effects more effectively.”

In the early stages of the pandemic, post-mortems on people who had died from severe COVID-19 infections showed changes in their brainstems, including inflammation.

Many of the changes were thought to result from a post-infection immune response, rather than direct virus invasion of the brain.

Rowe said: “People who were very sick early in the pandemic showed long-lasting brain changes, likely caused by an immune response to the virus.

“But measuring that immune response is difficult in living people.

“Normal hospital-type MRI scanners can’t see inside the brain with the kind of chemical and physical detail we need.”

Dr. Rua said: “With 7T scanners, we can now measure these details.

“The active immune cells interfere with the ultra-high magnetic field so that we’re able to detect how they are behaving.

“Cambridge was special because we were able to scan even the sickest and infectious patients, early in the pandemic.”

Many of the patients admitted to the hospital early in the pandemic reported fatigue, breathlessness and chest pain as troubling long-lasting symptoms.

The researchers hypothesized that those symptoms were in part the result of damage to key brainstem nuclei – damage which persists long after COVID-19 infection has passed.

The team saw that multiple regions of the brainstem, in particular the medulla oblongata, pons and midbrain, showed abnormalities consistent with a neuroinflammatory response.

The abnormalities appeared several weeks after hospital admission, and in regions of the brain responsible for controlling breathing.

Dr. Rua said: “The fact that we see abnormalities in the parts of the brain associated with breathing strongly suggests that long-lasting symptoms are an effect of inflammation in the brainstem following COVID-19 infection.

“These effects are over and above the effects of age and gender, and are more pronounced in those who had had severe COVID-19.”

The 7T scanners provided evidence of some of the psychiatric effects of the disease as well as the physical damage.

Rowe said: “Mental health is intimately connected to brain health, and patients with the most marked immune response also showed higher levels of depression and anxiety.

“Changes in the brainstem caused by COVID-19 infection could also lead to poor mental health outcomes, because of the tight connection between physical and mental health.”

The research team says their findings, published in the journal Brain, could aid in the understanding of other conditions associated with inflammation of the brainstem, such as MS and dementia.

They believe the 7T scanners could also be used to monitor the effectiveness of different treatments for brain diseases.

Dr. Rua added: “This was an incredible collaboration, right at the peak of the pandemic when testing was very difficult.

“I was amazed how well the 7T scanners worked.

“I was really impressed with how, in the heat of the moment, the collaboration between lots of different researchers came together so effectively.”

 

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