Ultra-powered MRI scans show damage to brain’s ‘control centre’ is behind long-lasting Covid-19 symptoms

Damage to the brainstem – the brain’s ‘control centre’ – is behind long-lasting physical and psychiatric effects of severe Covid-19 infection, the new study suggests.

Inflammation and the brain

The powerful MRI scanners used for the study, known as 7-Tesla or 7T scanners, can measure inflammation in the brain. Their results, published in the journal Brain, will help scientists and clinicians understand the long-term effects of COVID-19 on the brain and the rest of the body. Although the study was started before the long-term effects of COVID were recognised, it will help to better understand this condition.

The brainstem, which connects the brain to the spinal cord, is the control centre for many basic life functions and reflexes. Clusters of nerve cells in the brainstem, known as nuclei, regulate and process essential bodily functions such as breathing, heart rate, pain and blood pressure.

The study team partnered with the BioResource to identify and consent eligible patients, and scanned the brains of 30 people who had been admitted to hospital with severe Covid-19 early in 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.

Commenting on the role of the BioResource and our volunteers, the study's first author Dr Catarina Rua from the Department of Clinical Neurosciences at the University of Cambridge, said:

"We thank the BioResource group for their invaluable support in the recruitment of volunteers for this study.

"We recognise the particular difficulties that were experienced by individuals participating in clinical research in the context of the COVID-19 pandemic, and wish to thank the volunteers for their commitment to the research."

Immune response

In the early days of the Covid-19 pandemic, before effective vaccines were available, post-mortem studies of patients who had died from severe COVID-19 infections showed changes in their brainstems, including inflammation. Many of these changes were thought to result from a post-infection immune response, rather than direct virus invasion of the brain.

Dr Catarina Rua continues:

“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, but 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."

Professor James Rowe, also from the Department of Clinical Neurosciences, who co-led the research, says: 

"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"

The researchers 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 Catarina Rua: 

"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."

In addition to the physical effects of COVID-19, the 7T scanners provided evidence of some of the psychiatric effects of the disease. The brainstem monitors breathlessness, as well as fatigue and anxiety.

Professor James Rowe concludes: 

"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."

Understanding and collaboration

The researchers say the results could aid in the understanding of other conditions associated with inflammation of the brainstem, like MS and dementia. The 7T scanners could also be used to monitor the effectiveness of different treatments for brain diseases.

Dr Catarina Rua says:

"This was an incredible collaboration, right at the peak of the pandemic, when testing was very difficult, and 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."

The research was supported in part by the NIHR Cambridge Biomedical Research Centre, the NIHR Oxford Biomedical Research Centre, and the University of Oxford COVID Medical Sciences Division Rapid Response Fund.

The research team and the BioResource would like to thank the patient volunteers who consented to join the COVID-19 BioResource and to take part in this study.

Reference: Quantitative susceptibility mapping at 7 T in COVID-19: brainstem effects and outcome associations.