Date of Award

11-21-2024

Document Type

Dissertation

Degree Name

Ph.D.

Organizational Unit

College of Natural Science and Mathematics, Biological Sciences

First Advisor

Daniel Linseman

Second Advisor

Ann Wehman

Third Advisor

Scott Barbee

Fourth Advisor

Yan Qin

Fifth Advisor

Kim Gorgens

Copyright Statement / License for Reuse

All Rights Reserved
All Rights Reserved.

Keywords

COVID-19, Mild traumatic brain injury (mTBI), Chronic syndrome, Lyme disease, Neurological health

Abstract

Despite recent advances in our knowledge of COVID-19 and mild traumatic brain injury (mTBI), their combined effects remain incompletely understood. Recent studies have shed light on the complex interplay between these conditions. While initial research, including our own, focused on developing reliable antibody detection tests, subsequent investigations have focused on understanding the etiology of Long COVID, a chronic post-infection symptom syndrome affecting ~6% of US adults (Ford ND, 2023). COVID- 19 causes a state of heightened neuroinflammation in astrocytes and microglia, like the neuroinflammatory state observed after mTBI.

Parallel research on Lyme disease, the most prevalent vector-borne disease in the United States, is also associated with several complex and controversial post-infection symptom syndromes that are likely caused by immune dysfunction, inflammation, and/or auto-immunity. Here we report the results of a retrospective study that showed individuals with a combined history of Lyme disease and mTBI experienced more severe chronic neurological symptoms compared to those with either condition alone or healthy controls. This synergistic effect was associated with significant alterations in immune markers, energy metabolism markers, and hormones.

We also report the results of a prospective study on the combined effects of COVID-19 and mTBI. This study demonstrated that individuals with a combined history of infection and brain injury have worsened neurological and psychological symptoms, reduced quality of life, poorer self-reported cognitive performance, and changes in biomarkers related to immune function and neurodegeneration. Notably, astrocyte-derived exosomes (ADEs) from these patients induced inflammation in vitro, leading to reactive astrogliosis when injected into the brains of naïve mice. Additionally, bulk-proteomics analysis of primary human astrocytes incubated with patient ADEs from individuals with COVID-19 and mTBI cause changes in cellular pathways related to all major neurodegenerative diseases, suggesting that these individuals may have an increased risk.

Collectively, these studies highlight the profound impact of combined infection and injury on neurological health and provide important mechanistic and clinical insights that might lead to the development of new and critically needed targeted therapies and diagnostic treatments.

Copyright Date

11-2024

Publication Statement

Copyright is held by the author. User is responsible for all copyright compliance.

Rights Holder

Allison N. Grossberg

Provenance

Received from author

File Format

application/pdf

Language

English (eng)

Extent

356 pgs

File Size

895 MB

Download

Available for download on Thursday, January 21, 2027



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