Scientists believe they have discovered what is behind long Covid symptoms

Long Covid symptoms are caused by damage done by the infection to the brain’s ‘control centre’, a new scientific study has found.

Researchers from the Universities of Cambridge and Oxford were able to observe the damaging effects Covid-19 can have using ultra-high-resolution MRI scanners that can see the living brain in fine detail. The study scientists scanned the brains of 30 people admitted to hospital with severe Covid-19 early in the pandemic, before vaccines were available.

They discovered that Covid-19 infection damages the region of the brainstem associated with breathlessness, fatigue and anxiety. The brainstem, which connects the brain to the spinal cord, is the control centre for many basic life functions and reflexes.

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The results from the study, published in the journal Brain, will help scientists understand the long-term effects of Covid-19 on the brain and rest of the body.

The powerful MRI scanners used for the study, known as 7-Tesla or 7T scanners, measure inflammation in the brain - including clusters of nerve cells in the brainstem, known as nuclei, which regulate and process essential bodily functions such as breathing, heart rate, pain and blood pressure.

The study’s first author Dr Catarina Rua, from the Department of Clinical Neurosciences, 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.”

Professor James Rowe, also from the Department of Clinical Neurosciences, who co-led the research, added: “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.”

Early in the Covid-19 pandemic, before vaccines were available, post-mortem studies of patients who had died from severe coronavirus infections showed changes in their brainstems, including inflammation. These changes were thought to have come 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.”

“But with 7T scanners, we can now measure these details,” said Rua.

Many of the patients admitted to hospital early in the pandemic reported fatigue, breathlessness and chest pain as long-lasting symptoms. The researchers hypothesised these symptoms were in part the result of damage to key brainstem nuclei, damage which persists long after Covid-19 infection is gone.

The researchers saw that multiple regions of the brainstem 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.

“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,” said Rua.

The 7T scanners also provided evidence of some of the psychiatric effects of the disease. “Mental health is intimately connected to brain health, and patients with the most marked immune response also showed higher levels of depression and anxiety,” said Rowe. “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 researchers said the results could help in the understanding of other conditions associated with inflammation of the brainstem, such as MS and dementia. The scanners could also be used to monitor the effectiveness of different treatments for brain diseases.