An Interdisciplinary Study of SARS-Cov2's and Post-COVID-19 Syndrome Cellular and Clinical Considerations

Date of Award

2023

Degree Name

M.S. in Interdisciplinary Studies

Department

Interdisciplinary Studies (Department of Physical Therapy, Department of Biology)

Advisor/Chair

Kurt Jackson

Second Advisor

Mrigendra Rajput

Abstract

The SARS-CoV2 virus was responsible for the COVID-19 Pandemic, one of the most fatal international public health emergencies experienced in the past century. SARS-CoV2 induces symptoms like increased inflammatory response, severe acute respiratory syndrome (SARS), cognitive dysfunction like brain fog, and cardiovascular defects. Prolonged or long-term infection led to the emergence of Post-COVID-19 Syndrome, or PCS. PCS is characterized by chronic cardiovascular, autoimmune, and neurological manifestations and remains understudied. Individuals with pre-existing neurological insult like those with neuroinflammatory or neurodegenerative diseases are likely more vulnerable to such PCS effects. Furthermore, individuals with pre-existing neurological conditions often have comorbidities like obesity, hypertension, hyperlipidemia, and low activity levels. However, little is understood about the molecular effects of SARS-CoV2 on neuron in both healthy and neuro-compromised individuals. Currently, many individuals experiencing PCS-related neurological symptoms require management of their symptoms even though our knowledge in this area is still limited. Therefore, this study utilized an interdisciplinary approach to better understand how SARS-CoV2 impacts both neurons at a cellular level and clinically in neurologically compromised populations such as Multiple Sclerosis (MS). This interdisciplinary approach sheds light on how translational work is being done where basic science efforts complement efforts made clinically to make connections and identify relationships between observed effects and known science. To do so, SARS-CoV2 proteins were misexpressed in the Drosophila eye and through a forward genetic screen evaluated for changes to cellular structure or function. To corroborate these findings, SARS-CoV2 proteins were also transfected into Neuro-2a cells to assess how these proteins affected cellular functioning. Furthermore, SARS-CoV2 protein structure-function analysis was also assessed in a neurodegenerative background in Drosophila. We hypothesized that SARS-CoV2 proteins may influence such backgrounds by promoting or worsening neurodegenerative effects. To better understand the clinical implications of COVID-19 on individuals with prior neurological dysfunction, a literature review was conducted to explore the effects of COVID-19 in persons with multiple sclerosis (MS). In this review symptoms were grouped by domains (e.g., cardiovascular, respiratory) that were compromised along with common interventions and methods for assessing the impacts of COVID-19 and response to treatment interventions.

Keywords

Biomedical Research, Neurology, Neurosciences, Virology, Physical Therapy, SARS-CoV2 Neurological Effects, Alzheimer's Disease SARS-CoV2 Drosophila, Multiple Sclerosis SARS-CoV2, Cell death SARS-CoV2 Neuro-2a, Cell death in N2A post SARS-CoV2 infection, Neurodegeneration SARS-CoV2, PwMS COVID-19 Neurological Manifestations, SARS-CoV2 apoptosis, SARS-CoV2 autophagy, SARS-CoV2 necrosis

Rights Statement

Copyright © 2023, author

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