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COVID-19 Risks to the Brain

COVID-19 and Changes in Brain Structure
     Already, there has been strong evidence that COVID-19 infection can affect the brain as found by previous studies (See COVID-19 Affects the Brain) and instances of neurological cognitive deficits demonstrated by COVID-19 patients over time. Over 80% of these neurological cases, however, occur in patients with severe cases of COVID-19 and much less is known about the neurological impact of COVID-19 infection in milder cases. A recent study, published on March 7, 2022 in the journal Nature, investigated brain changes in United Kingdom patients with mild and severe cases of COVID-19.

About the Study

    The study was conducted by a group of researchers from the University of Oxford aiming to answer the question of whether COVID-19 infection is associated with changes in brain structure. A total of 785 participants (data taken from UK Biobank) aged 51-81 participated in the study. All participants underwent two brain scans roughly three years apart, in addition to some basic cognitive testing. In between their two scans, 401 participants tested positive for the coronavirus between March 2020 and April 2021. Among the 401 COVID-19 positive participants, only 15 were hospitalized, while the other 386 participants had mild symptoms. The study also included another 384 participants to form a control group that had not been infected with the coronavirus and had similar characteristics to the infected patients in areas like age, sex, medical history and socioeconomic status. 

    A unique aspect of the study is the availability of brain scans taken both before and after infection. This is significant as pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects and allows scientists to, in the most accurate way possible, analyze the effects of COVID-19 on the brain. The infected patients in the study underwent a second brain scan an average of 141 days after their infection. 


Study Results

    To the surprise of many people, the study found that COVID-19 may cause a greater loss of gray matter and tissue damage in the brain than what naturally occurs in people who have not been infected with the virus. The shrinkage and tissue damage were found to primarily be in areas of the brain related to sense of smell, as well as other functions.

    With normal aging, people lose a tiny fraction of gray matter each year. In regions related to memory, the typical annual loss is between 0.2% and 0.3%. However, COVID-19 patients in the study experienced between 0.2% and 2% of additional gray matter loss in different regions of the brain over the three years between scans. These participants also lost more overall brain volume and showed more tissue damage in certain areas. Although some of the largest gray matter loss was in areas related to smell, including the orbitofrontal cortex and parahippocampal gyrus, those areas are also involved in memory and other functions. The results also found that the 15 hospitalized patients in the study had much worse brain atrophy than the mildly infected patients. 

    Notably, these neurological effects of COVID-19 are very generalized as the majority of Covid patients were only mildly affected by their initial Covid infection. In addition to brain shrinkage, participants with COVID-19 also showed a greater decline on a cognitive test related to attention and efficiency in performing a complex task compared to the control group.


Discussion and Implications

    This is the first longitudinal imaging study comparing brain scans from individuals both before and after COVID-19 infection to scans from a well-matched control group. The study’s unique design provides convincing evidence that COVID-19 infection results in changes in the brain. While the exact cause of the brain changes are unclear, the authors mentioned theories including inflammation (evidence of which has been found in other studies), and sensory deprivation from a disrupted sense of smell. However, it remains unknown if these changes have any long-term clinical implications for the patients. Whether this deleterious impact can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow-up studies.

Sources

1. Douaud, G., Lee, S., Alfaro-Almagro, F. et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature (2022). https://doi.org/10.1038/s41586-022-04569-5


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