Recent ultra-detailed MRI scans have unveiled that severe COVID-19 can cause significant damage to the brainstem, a critical area responsible for essential functions such as breathing. Previous research has indicated that COVID-19 affects brain health, but the specifics remained unclear until now.
A new study harnesses cutting-edge scanning technology to delve into these effects, suggesting that the brainstem damage linked to COVID-19 infection may explain some long COVID symptoms, including persistent breathlessness and brain fog.
While scientists have previously struggled to pinpoint the exact brain changes related to long-term COVID symptoms, this study shifts the focus to the brainstem, which is vital for controlling various autonomic functions, including respiration.
Impact on the Brainstem
The study identifies distinct changes in the brainstem of individuals who were hospitalized due to COVID-19, with damage more pronounced in those who experienced severe disease. These findings are published in the journal Brain.
Earlier studies indicated that severe SARS-CoV-2 infections could lead to various brain alterations, such as microhemorrhages, encephalopathy (manifesting as confusion and memory loss), and white matter hyperintensities—anomalies linked to dementia. Research also pointed to potential changes in the brainstem, which connects the brain and spinal cord, regulating many life-sustaining functions.
Dr. Catarina Rua, a research associate in the Department of Clinical Neuroscience at the University of Cambridge, emphasized the importance of the brainstem’s role in controlling vital autonomic functions that we do not consciously manage.
Some researchers have suggested that damage to the brainstem could contribute to long COVID symptoms, including fatigue, brain fog, breathlessness, and mental health changes. However, prior studies failed to consistently show brainstem abnormalities over time.
Advancements in Imaging Technology
Utilizing ultra-high field (7T) quantitative susceptibility mapping, the researchers were able to detect subtle changes in the brainstem. Dr. Rua explained that 7T MRI scanners offer increased sensitivity compared to standard 3T scanners, allowing them to examine the brainstem at resolutions below a cubic millimeter, which is crucial for identifying microscopic changes.
The study involved scanning the brains of 30 patients who had been hospitalized with severe COVID-19, with scans conducted between 93 and 548 days post-treatment. These scans were compared to those of 51 age-matched individuals who had not contracted the virus.
The analysis revealed significant abnormalities in the major regions of the brainstem—the medulla oblongata, pons, and midbrain—linked to inflammation. The differences observed between healthy participants and those affected by COVID-19 were consistent with a neuroinflammatory response, particularly in the medullary reticular formation, a region crucial for regulating breathing.
Dr. Rua highlighted that abnormalities in areas associated with respiratory control strongly suggest that the long-term symptoms may be a consequence of inflammation in the brainstem following COVID-19.
Additionally, the study noted that individuals who had experienced the highest levels of inflammation during their COVID-19 illness exhibited more pronounced brainstem abnormalities, while those with less severe cases and shorter hospital stays had fewer such changes.
Pathways of Infection
MNT also consulted Dr. Jeffrey Langland, a research professor at Sonoran University of Health Sciences, regarding how SARS-CoV-2 might reach the brain. He explained that the virus can infect olfactory neurons, which then transport it from the nasal cavity to the central nervous system (brain and spinal cord). Once inside the central nervous system, the virus can infect cells using the ACE-2 receptor, leading to potential damage that may result in long COVID.
However, the new study’s authors clarify that the virus does not necessarily need to enter the brain directly to inflict damage on the brainstem. In most instances, there is no evidence of direct viral infection in the central nervous system; instead, the inflammation observed in the brainstem appears to be a response to the overall infection in the body.
Ongoing Research and Future Questions
Despite its valuable insights, the study has limitations, including its small sample size due to recruitment challenges at the onset of the pandemic, prior to the availability of COVID-19 vaccines. Additionally, the brain scans were conducted only once, suggesting that longitudinal studies could shed more light on whether the identified brainstem abnormalities persist over time.
Dr. Langland noted that while this research enhances our understanding of the mechanisms by which the virus causes brain damage, further exploration is necessary to develop strategies for preventing or repairing that damage.
Dr. Rua and her team are committed to continuing their research, having collected extensive data from participants during the post-hospitalization recovery phase. They are also hopeful that the advanced 7T scanning technology will provide new insights into other neurological conditions involving inflammation in the brainstem, such as multiple sclerosis.
