Advancing Clinical Practices and Patient Outcomes Through Computational Analyses in Medicine: A Focus on SARS-CoV-2 Epidemiology, COVID-19, and Long-COVID Neuropathogenesis
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Authors
Khan, Majid
Issue Date
2023
Type
Dissertation
Language
Keywords
Computational Analyses , COVID-19 , long-COVID , Neurosurgery , Public Health , SARS-CoV-2
Alternative Title
Abstract
This dissertation comprehensively explores Severe Acute Respiratory SyndromeCoronavirus 2 (SARS-CoV-2) and its implications. In particular, SARS-COV-2 effects on
Coronavirus Disease 2019 (COVID-19), disease severity, long-COVID pathogenesis,
neurological sequelae (i.e., post-acute sequelae SARS-CoV-2 infection [PASC]), and
patient health outcomes are explored. A deep focus is on investigating specific SARSCoV-
2 variants that are the more prevalent and cause worsened COVID-19 and long-
COVID disease severity, along with examining SARS-CoV-2 effects on latent
herpesvirus (HHV) reactivation. In addition, we investigate the impact of the COVID-19
pandemic on the quality of life of patients undergoing treatment for gliomas.Investigation of SARS-CoV-2 through wastewater-based-epidemiology (WBE) inthe Reno-Sparks metropolitan region provided a broad overview of the status of COVID-
19 and the circulating SARS-CoV-2 variants and pathogens in the region. We investigated
COVID-19 patients by analyzing nasopharyngeal (NP) swab specimens using Next-
Generation RNA Seq and analyzed cellular and molecular characteristics, gene
disturbances, and cellular pathways. We correlated these findings with important patient
factors (e.g., comorbidities, age, gender, vaccination/booster status, symptoms, and
disease progression timelines).We identified SARS-CoV-2 variants during primary infection, which resulted inworsened severity of COVID-19 infection and patient outcomes. Notably, we found
underlying human herpes viruses (HHVs) in some nasopharyngeal specimens, prompting
further investigation into the molecular mechanisms involved in SARS-CoV-2-induced
reactivation of latent HHVs. This line of inquiry yielded insights into the potential
interplay between HHVs, SARS-CoV-2 variants, and patient outcomes. These analyses
supplied insights to improve patient and public health outcomes for COVID-19 patients
and those with underlying HHVs. Our literature investigation highlighted the molecular
underpinnings involved in the role of SARS-CoV-2 infection, COVID-19 disease, and its
effect on underlying HHVs.In the context of glioma patients, we explored the impact of the COVID-19pandemic on their treatment outcomes and quality of life. We analyzed preliminary data
from a cohort of patients from the University of Utah (U of U) Department of
Neurosurgery (Salt Lake City, UT) enrolled in a clinical trial for glioma treatment; some
underwent surgery and completed study questionnaires before and during the pandemic.
Notably, poor prognosis in gliomas may result from certain pandemic-influenced factors
and, thus, can be targeted to improve the treatment of gliomas and clinical outcomes.
Furthermore, we investigated the molecular determinants and mechanisms involved in
long-COVID neuropathogenesis. We report preliminary cohort analyses, including
clinical variables and SARS-CoV-2 variants at COVID-19 primary or repeat infection
and their association with severity. We also describe the future directions of two studies,
evaluating serum proteins and functional-MRI (fMRI) changes in long-COVID patients
with neurological symptoms and evaluating glioma patients' quality of life concerning
specific tumor biomarkers and imaging data.Published abstracts and manuscripts are appended at the end of the dissertation.These underscore the application of these computational analyses to yield improvement
in patient health outcomes. Our findings highlight the implications of infectious diseases
on our health to improve clinical practices and patient outcomes.