Mechanical Oxygen, Fever Linked to Gray Matter Volume Reductions in COVID-19 Patients

COVID-19 patients who experience fever or who receive oxygen during treatment have reduced levels of gray matter volume (GMV) in the frontal-temporal part of the brain even six months after discharge.

Throughout the pandemic, brain MRI and CT results have shown that roughly one-third of COVID-19-positive patients experience neurological impacts. The results of this new study, published in the May issues of Neurobiology of Stress, reveal that the gray matter in the frontal network could be a core brain region for viral involvement – even more so than identified clinical manifestations, such as stroke.

According to investigators from Georgia State University and the Georgia Institute of Technology, this is the first research attempt to examine CT-derived GMV alterations underlying COVID-19 by using a multivariate analytical approach. The team is also associated with the Center for Translational Research in Neuroimaging and Data Science (TReNDS).

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“Science has shown that the brain’s structure affects its function, and abnormal brain imaging has emerged as a major feature of COVID-19,” said first author Kuaikuai Duan, a graduate research assistant at TReNDS and doctoral student in Georgia Tech’s School of Electrical and Computer Engineering. “Previous studies have examined how the brain is affected by COVID-19 using a univariate approach, but ours is the first to use a multivariate, data-driven approach to link these changes to specific COVID-19 characteristics and outcome.”

For their study, the team analyzed CT scans from 120 age-, gender-, and disease-matched patients who were hospitalized for neurological diseases – 58 patients had acute COVID-19 infection, and 62 were not infected with the virus. The images were captured between one-and-17 days post COVID-19 diagnosis, and to augment the statistical power of the study, the team used source-based morphometry analysis.

Based on their evaluation, the team determined that patients who had lower GMV in the superior, medial, and middle frontal gyri at discharge and six months later had higher levels of disability. In addition, they also identified that COVID-19 patients who received mechanical oxygen also had significant GMV reductions compared to those who did not have the virus (p=1.73x10^-2, t= -2.46, DF=54). The situation was similar among COVID-19 patients who experienced fever when compared those COVID-19 patients who did not (p=9.44x10^-3, t= -2.69, DF=54).

These results, they said, indicate that the virus may affect the frontal-temporal network through lack of oxygen or fever. They add to the growing body of findings from MRI, CT, EEG, and FDG-PET scans that show these lobes are affected by the virus, the team said.

This GMV reduction could also explain some of the changes in mood frequently seen in COVID-19 patients, they said, because diminished gray matter in these areas of the brain is also associated with agitation in patients.

“Neurological complications are increasingly documented for patients with COVID-19,” said senior author Vince Calhoun, Ph.D., psychology professor at Georgia State with and engineering appointment at Georgia Tech and neurology and psychiatry appointments at Emory University. “As reduction of gray matter has also been shown to be present in other mood disorders, such as schizophrenia and is likely related to the way that gray matter influences neuron function.”

Given the nature of their results, the team said frontal-temporal network changes could be a biomarker that could help providers determine a prognosis for COVID-19-positive patients or play into deciding upon the most appropriate treatment path. As a next step, the team plans to repeat the study on a larger sample size with many types of brain scans from different COVID-19 patient groups.

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