Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Medical Biophysics

Supervisor

Dr. Robert Bartha

Abstract

The long-term neuropsychological, cognitive, and neurobiological effects of the severe acute respiratory syndrome (SARS-CoV-2) in survivors with milder symptoms are still poorly understood. In this thesis we evaluated cognitive and psychological changes approximately five weeks after a wide range of symptoms in COVID-19 illness and determined whether advanced diffusion magnetic resonance imaging measures within subcortical brain structures of the limbic system were related to neurological, respiratory, psychiatric, and gastric symptoms experienced during the acute phase of illness. Cognitive and neuropsychological evaluations were performed in 45 participants who experienced neurological symptoms during the acute phase of COVID-19 illness. Participants also underwent a 7 Tesla MRI neurological exam on the same day. The group showed a significant reduction in attention compared to a normative population, but no differences in other cognitive domains. Although white matter hyperintensities were visible on fluid attenuated inversion recovery (FLAIR) images in 22 of 43 participants consistent with small vessel ischemic disease and migraine, this incidence is consistent with that expected in a normative population. Participants were divided into groups based on the presence or absence of symptoms at their acute illness from the medical history collected over the phone or in-person during recruitment. No differences were observed in subcortical brain structure volumes when comparing participants between subgroups. Differences in advanced diffusion metrics were observed within several subcortical structures (p<0.0036, Bonferroni corrected Mann-Whitney U-test) when comparing groups suggesting subtle tissue changes in several regions that were mostly related to respiratory and gastric symptoms. There were no strong associations between diffusion measurements and attention. Future studies should follow participants longitudinally to determine whether the observed changes persist.

Summary for Lay Audience

We have struggled with coronavirus disease 2019 or COVID-19 since December 2019. This virus led to a pandemic because it has spread worldwide and affected many people. It impacted the world from a health and economic perspective and motivated scientists from all over the world to investigate the illness to minimize the risks to future human health.

Although COVID-19 starts by infecting the respiratory system, it causes a range of symptoms and affects many different organs, including brain. In this thesis, we investigate the long-term cognitive effects and imaging changes of COVID-19 infection in the brain within 45 patients with mostly mild symptoms after they have recovered from the respiratory symptoms. We used a very high magnetic field strength MRI scanner to acquire images of the brain for this study to better understand subtle changes in brain tissue.

To evaluate cognition, we compared COVID-19 survivors in the study using standardized questionnaires with data from a normative group that included healthy adolescents and adults. The results showed that patients who recovered from COVID-19 illness had attention deficits. In some patients, we observed minor changes in the MRI scans indicating some disease processes, but these were mostly consistent with what we would expect in a control group of people at the same age. Since we did not have access to baseline brain imaging, we cannot say that these abnormalities are directly related to the COVID-19 infection.

We also used more advanced diffusion MRI techniques to investigate microstructural changes in the brain. Here, we did find some changes within the brain tissue when comparing groups with and without specific symptoms that the patients experienced during their acute illness.

In summary, this study found changes in attention about five weeks (138±54 days) after COVID-19 illness and subtle differences in some measures of tissue microstructure in the brain. Larger studies are needed to confirm these findings and to determine if these changes persist.

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