A study indicates that damage to the brainstem, which acts as the ‘control center’ of the brain, is responsible for the prolonged physical and psychiatric effects of severe Covid-19 infections.
Researchers from the Universities of Cambridge and Oxford utilized advanced ultra-high-resolution scanners that can capture detailed images of the living brain to examine the harmful effects that Covid-19 can inflict on the brain.
The research team analyzed the brain scans of 30 individuals who were hospitalized due to severe Covid-19 early in the pandemic, before vaccines became available. They discovered that the Covid-19 infection negatively affects the brainstem area linked to symptoms such as breathlessness, fatigue, and anxiety.
Using powerful MRI machines called 7-Tesla or 7T scanners, the researchers measured inflammation levels in the brain. Their findings, published in the journal Brain, will assist scientists and healthcare professionals in understanding the long-term impacts of Covid-19 on both the brain and the body. Although this research began prior to the widespread acknowledgment of Covid-19’s long-term effects, it serves to enhance our understanding of this condition.
The brainstem connects the brain to the spinal cord and regulates many essential life functions and reflexes. Nerve cell clusters known as nuclei within the brainstem are crucial for managing and processing vital bodily functions like breathing, heart rate, pain sensation, and blood pressure.
“Changes within and around the brainstem are essential for maintaining quality of life, yet it has previously been challenging to observe inflammation in the brainstem nuclei of living individuals due to their small size and difficult positioning,” stated Dr. Catarina Rua, the study’s lead author from the Department of Clinical Neurosciences. “Typically, we gain insights into the brainstem only during post-mortem examinations.”
“The brainstem serves as a key junction linking our conscious awareness to our body’s functions,” explained Professor James Rowe, also from the Department of Clinical Neurosciences and co-leader of the research. “Understanding how the brainstem adapts to Covid-19 will allow for more effective explanations and treatments of its long-term effects.”
Early in the Covid-19 pandemic, prior to the availability of effective vaccines, post-mortem examinations of patients who succumbed to severe Covid-19 revealed changes in their brainstems, including inflammation. Many of these alterations were believed to stem from the body’s immune response to the infection, rather than direct viral invasion of the brain.
“Patients who were severely ill in the early days of the pandemic exhibited enduring brain changes likely caused by an immune response to the virus. However, assessing this response in living patients is challenging,” said Rowe. “Conventional hospital MRI machines lack the sensitivity needed to explore the brain at the required chemical and physical levels.”
“The 7T scanners enable us to gather these vital details. The active immune cells interfere with the ultra-high magnetic field, allowing us to monitor their behavior,” Rua added. “Cambridge’s unique capability allowed us to scan even the most critically ill and infectious patients at that early stage of the pandemic.”
Many patients hospitalized during the early pandemic reported persistent symptoms like fatigue, breathlessness, and chest pain. The researchers believed these symptoms were partially due to damage in crucial brainstem nuclei, which remains after the Covid-19 infection has resolved.
The research revealed that various brainstem regions, particularly the medulla oblongata, pons, and midbrain, displayed abnormalities consistent with a neuroinflammatory response. These abnormalities emerged several weeks after the patients were admitted to the hospital, particularly in areas of the brain responsible for regulating breathing.
“The identification of irregularities in the brain areas associated with breathing strongly indicates that these prolonged symptoms result from inflammation in the brainstem post-Covid-19 infection,” said Rua. “These effects transcend factors like age and gender, being especially pronounced in those who suffered severe Covid-19.”
Beyond the physical impacts, the 7T scanners also revealed evidence of the psychiatric effects related to Covid-19. The brainstem is responsible for monitoring aspects such as breathlessness, fatigue, and anxiety. “Mental health is closely linked to brain health. Patients showing pronounced immune responses also reported increased levels of depression and anxiety,” remarked Rowe. “Changes in the brainstem due to Covid-19 could adversely affect mental health outcomes due to the strong connection between physical and psychological well-being.”
The findings may also deepen the understanding of other inflammation-related conditions affecting the brainstem, like multiple sclerosis and dementia. Moreover, the 7T scanners could be pivotal in tracking the effectiveness of various treatments for brain diseases.
“This collaboration was remarkable, especially during the peak of the pandemic when testing posed significant challenges, and I was impressed with the performance of the 7T machines,” reflected Rua. “The cooperation among diverse researchers in such trying times was truly impressive.”
This research received partial support from the NIHR Cambridge Biomedical Research Centre, the NIHR Oxford Biomedical Research Centre, and the University of Oxford COVID Medical Sciences Division Rapid Response Fund.
