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As the return to normality in the wake of the COVID-19 pandemic enters its early stages, the necessity for accurate, quick, and community-wide surveillance of SARS-CoV-2 has been emphasized. Wastewater-based epidemiology (WBE) has been used across the world as a tool for monitoring the pandemic, but studies of its efficacy

As the return to normality in the wake of the COVID-19 pandemic enters its early stages, the necessity for accurate, quick, and community-wide surveillance of SARS-CoV-2 has been emphasized. Wastewater-based epidemiology (WBE) has been used across the world as a tool for monitoring the pandemic, but studies of its efficacy in comparison to the best-known method for surveillance, randomly selected COVID-19 testing, has limited research. This study evaluated the trends and correlations present between SARS-CoV-2 in the effluent wastewater of a large university campus and random COVID-19 testing results published by the university. A moderately strong positive correlation was found between the random testing and WBE surveillance methods (r = 0.63), and this correlation was strengthened when accommodating for lost samples during the experiment (r = 0.74).

ContributorsWright, Jillian (Author) / Halden, Rolf (Thesis director) / Driver, Erin (Committee member) / School of Music, Dance and Theatre (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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In mid-March of 2020, Arizona State University transformed one of its research labs into ASU Biodesign Clinical Testing Laboratory (ABCTL) to meet the testing needs of the surrounding community during the COVID-19 pandemic. The lab uses RT-qPCR, or reverse transcription polymerase chain reaction, to match the components of a biosample

In mid-March of 2020, Arizona State University transformed one of its research labs into ASU Biodesign Clinical Testing Laboratory (ABCTL) to meet the testing needs of the surrounding community during the COVID-19 pandemic. The lab uses RT-qPCR, or reverse transcription polymerase chain reaction, to match the components of a biosample to a portion of the SARS-CoV-2 genome. The ABCTL uses the TaqPath™ COVID-19 Combo Kit, which has undergone many different types of efficacy and efficiency tests and can successfully denote saliva samples as positive even when an individual is infected with various emerging strains of the SARS-CoV-2. Samples are collected by volunteers at testing sites with stringent biosafety precautions and processed in the lab using specific guidelines. As the pandemic eventually becomes less demanding, the ABCTL plans to utilize the Devil’s Drop-off program at various school districts around Arizona to increase testing availability, transfer to the SalivaDirect method, and provide other forms of pathogen testing to distinguish COVID-19 from other types of infections in the ASU community.

ContributorsAnderson, Laura (Co-author) / Ruan, Ellen (Co-author) / Smetanick, Jennifer (Co-author) / Majhail, Kajol (Co-author) / Breshears, Scott (Co-author) / Compton, Carolyn (Thesis director) / Magee, Dewey (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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On March 11th, COVID-19 was declared a pandemic by the World Health Organization. The ensuing months saw an extensive allocation of resources toward combating the virus and the development of a vaccine. Despite extensive research on SARS-CoV-2, there remains little information regarding the implications of SARS-CoV-2 gastrointestinal shedding on COVID-19

On March 11th, COVID-19 was declared a pandemic by the World Health Organization. The ensuing months saw an extensive allocation of resources toward combating the virus and the development of a vaccine. Despite extensive research on SARS-CoV-2, there remains little information regarding the implications of SARS-CoV-2 gastrointestinal shedding on COVID-19 disease. It is hypothesized that SARS-CoV-2 RNA is shed in the stool for up to several weeks and that viral protein persists in the GI tract. This study also explored calprotectin and zonulin levels, markers of inflammation, and intestinal permeability, respectively, to assess if increased viral shedding is associated with elevated levels of either. This study utilized RT-qPCR assays to confirm the presence of viral RNA. Subsequently, RT-qPCR positive samples were heat-inactivated and SARS-CoV-2 spike detection enzyme-linked immunosorbent assay (ELISA) was used to ascertain viral protein shedding. Additional ELISA was performed to assess zonulin and calprotectin levels. Results indicated that 30 of the 758 unique samples were confirmed SARS-CoV-2 positive by RT-qPCR. Spike protein was ultimately not detected by ELISA. Additionally, no significant increase in zonulin was observed in patient samples when comparing RT-qPCR positive and negative Samples. A notable upwards trend approaching significance in calprotectin levels existed for patients who tested positive for SARS-CoV-2 by RT-qPCR, though, it was found that no correlation existed between SARS-CoV-2 copy number and calprotectin levels. Understanding the interaction between SARS-CoV-2 and the GI tract may therefore have significant clinical implications and this study demonstrates the need for additional studies to garner a more comprehensive understanding.

ContributorsKhan, Adam (Author) / Lim, Efrem (Thesis director) / Li, Yize (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of International Letters and Cultures (Contributor)
Created2022-05
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Description
The work in this dissertation progressed the research of structural discovery for two targets critical in the fight of infectious disease. Francisella lipoprotein 3 (Flpp3) is a virulent determinant of tularemia and was the first protein of study. The proteins soluble domain was studied using a hybrid modeling theory that

The work in this dissertation progressed the research of structural discovery for two targets critical in the fight of infectious disease. Francisella lipoprotein 3 (Flpp3) is a virulent determinant of tularemia and was the first protein of study. The proteins soluble domain was studied using a hybrid modeling theory that used small angle X-ray scattering (SAXS) in combination with computation analysis to generate a SAXS-refined structure. The SAXS-refined structure closely resembled the NMR structure (PDB: 2MU4) which contains a hydrophobic cavity inside the protein that could be used for drug discovery purposes. The full-length domain of Flpp3 purified from the outer membrane of E. coli was also studied with a combination of biophysical characterization methods. Mass spectrometry and western blot analysis confirmed Flpp3 being translocated to the outer membrane, while SDS-PAGE confirmed the purity of Flpp3 in the monomeric form after size exclusion chromatography. Using Circular Dichroism (CD) the monomeric form of Flpp3 was shown to be almost fully refolded into having a primarily β-stranded secondary structure. This information advances the progress of both tularemia research and outer membrane protein research as no natively folded outer membrane protein structures have been solved for F. tularensis.The second protein worked on in this dissertation is the nonstructural protein 15 from SARS-CoV-2, also called NendoU. Nsp15 is an endoribonuclease associated with aiding the virus responsible for the current COVID-19 pandemic in evasion of the immune system. An inactive mutant of Nsp15 was studied with both negative stain electron microscopy and cryogenic electron microscopy (Cryo-EM) in the presence of RNA or without RNA present. The initial findings of negative stain electron microscopy of Nsp15 with and without RNA showed a difference in appearance. Negative stain analysis of Nsp15 is in the presence of a 5nt RNA sequence in low salt conditions shows a conformational change when compared to Nsp15 without RNA present. As well the presence of RNA appeared to shift the electron density in Cryo-EM studies of Nsp15. This work advances the research in how Nsp15 may bind and cleave RNA and aid in the evasion of the host cell immune system.
ContributorsGoode, Matthew (Author) / Fromme, Petra (Thesis advisor) / Guo, Jia (Committee member) / Chiu, Po-Lin (Committee member) / Arizona State University (Publisher)
Created2022
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Description
Infectious diseases are the third leading cause of death in the United States and the second leading cause of death in the world. This work aims to advance structural studies of vital proteins involved in the infection process of both a bacterial and a viral infectious disease in hopes of

Infectious diseases are the third leading cause of death in the United States and the second leading cause of death in the world. This work aims to advance structural studies of vital proteins involved in the infection process of both a bacterial and a viral infectious disease in hopes of reducing infection, and consequently, fatality rates. The first protein of interest is OspA, a major outer surface protein in Borrelia burgdorferi – the causative bacterium of Lyme disease. Previous functional studies of OspA allude to both a role in colonization of B. burgdorferi in the tick vector and in evasion of the human immune system. This work describes the first ever structural studies of OspA as it is seen by the immune system: in the outer membrane. OspA was expressed in and purified from the outer membrane of Escherichia coli prior to characterization via circular dichroism (CD), native polyacrylamide gel electrophoresis, and electron microscopy. Characterization studies of OspA provide the first evidence of multimeric formation of OspA when translocated to the outer membrane, which presents a new perspective from which to build upon for the design of vaccinations against Lyme disease. The second protein of interest is nonstructural protein 15 (Nsp15), a protein responsible for facilitating immune system evasion of SARS-CoV-2 – the virus responsible for the COVID-19 pandemic. Nsp15 functions to enzymatically cleave negative sense viral RNA to avoid recognition by the human immune system. The work described in this dissertation is dedicated to the electron microscopy work utilized to reveal structural information on an inactive variant of Nsp15 bound to RNA sequences. Negative stain electron microscopy was used to verify Nsp15 structural integrity, as well as reveal a low-resolution image of structural deviation when RNA is bound to Nsp15. Cryo-electron microscopy was performed to solve structural density of Nsp15 without RNA to a resolution of 3.11 Å and Nsp15 bound to 5-nucleotides of RNA to a resolution of 3.99 Å. With further refinement, this structure will show the first structural data of Nsp15 bound to a visible RNA sequence, revealing information on the binding and enzymatic activity of Nsp15.
ContributorsKaschner, Emily (Author) / Fromme, Petra (Thesis advisor) / Hansen, Debra T (Committee member) / Chiu, Po-Lin (Committee member) / Arizona State University (Publisher)
Created2022
Description

Survivors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often experience chronic symptoms that include fatigue, shortness of breath, and brain fog. The collection of ongoing post-COVID-19 symptoms have been classified as Post-Acute Sequela of SARS-CoV-2 (PASC). Older adult patients are especially susceptible to experiencing PASC related complications and have

Survivors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often experience chronic symptoms that include fatigue, shortness of breath, and brain fog. The collection of ongoing post-COVID-19 symptoms have been classified as Post-Acute Sequela of SARS-CoV-2 (PASC). Older adult patients are especially susceptible to experiencing PASC related complications and have a high risk for long-term cognitive impairment symptoms. Definitions for categorizing PASC- associated cognitive impairment and neuropsychological assessments used to evaluate cognitive impairment are inconsistent between studies examining older adults. This systematic review aims to identify which neuropsychological tests best identify cognitive impairments associated with PASC and suggest a guide to standardize the measurement of PASC-related cognitive impairments. Through a literature search using PubMed, we included within this review 14 studies that fulfilled our inclusion and exclusion criteria evaluating middle-aged and older adult populations affected by PASC-associated cognitive impairments. The majority of the studies used tests designed to screen for general cognitive function to test for the prevalence of cognitive impairment, with the most common one being Montreal Cognitive Assessment (MoCA), followed by MMSE and TICS. MoCA reported the highest prevalence of the general cognitive screeners which suggests higher sensitivity and specificity. Telephone Interview for Cognitive Status (TICS) demonstrated similar scores as MoCA despite administration being remote while MMSE identified the lowest prevalence. Four studies also used domain-specific cognitive evaluations and reported instances of cognitive impairment in individuals who had previously tested healthy. Furthermore, the results gathered in this review were stratified based on disease symptom severity. This review identifies MoCA to be better suited for evaluating general cognitive impairment in older adults. TICS has the added utility in being able to access a wider range of older adults through remote screening. Disease severity must be clearly defined to allow better comparisons between studies and allow for standardization. Early identification of PASC-associated cognitive impairment in middle-aged and older adults can be performed using general cognitive function evaluations and administering a baseline cognitive evaluation one month after infection is suggested.

ContributorsCuc, Nicklus (Author) / Ng, Ted (Thesis director) / Maxfield, Molly (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Department of Psychology (Contributor)
Created2023-05
Description

The article highlights the damage COVID-19 can cause by attacking brain tissue which can lead to several neurological disorders; it is a collection of systematic review and meta-analysis reviews as well as different scientific studies. The article addresses the background of COVID-19 and the distinction between Long COVID and COVID-19,

The article highlights the damage COVID-19 can cause by attacking brain tissue which can lead to several neurological disorders; it is a collection of systematic review and meta-analysis reviews as well as different scientific studies. The article addresses the background of COVID-19 and the distinction between Long COVID and COVID-19, along with the general pathway that the virus of COVID-19 takes to infect a cell at a cellular level. The variety of symptoms that individuals experience can be a topic of interest, and this article discusses the variability in COVID-19 infection. Moreover, SARS-COV-2 can enter the body in different ways and attack different types of cells within the body, thus the article brings attention to the different mechanisms of infection. Due to the brain damage that can be caused by COVID-19, there are several neurological disorders the article addresses including status epilepticus, stroke, acute necrotizing encephalopathy, encephalitis, hypogeusia, hyposmia, guillain-barre syndrome, and systemic inflammatory response syndrome. Although these disorders have different routes of treatment, the article briefly talks about general treatments for COVID-19 that include antiviral drugs, immune modulators, and monoclonal antibody treatment. Given the significance of COVID-19, more research should be done to understand the variety of neurological disorders that can be an effect of COVID-19 infection.

ContributorsMunn, Rebecca (Author) / Merkley, Ryan (Thesis director) / Melkozernov, Alexander (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2023-05
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Description
Coronavirus disease 2019 (COVID-19), an illness caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), has been responsible for significant social and economic
disruption, prompting an urgent search for therapeutic solutions. The spike protein of the virus
has been examined as an immunogenic target because of its role in viral binding and fusion
necessary

Coronavirus disease 2019 (COVID-19), an illness caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), has been responsible for significant social and economic
disruption, prompting an urgent search for therapeutic solutions. The spike protein of the virus
has been examined as an immunogenic target because of its role in viral binding and fusion
necessary for infection of host cells. Previous studies have identified a recombinant protein
(denoted as S1) that has been shown to potentially induce a neutralizing antibody response by
mimicking the structure of the SARS-CoV-2 spike protein. We have produced the S1 in plants
using agroinfiltration, a plant transformation technique whereby plasmid-containing
Agrobacterium tumefaciens is injected into Nicotiana benthamiana plants, resulting in transfer of
the desired gene from bacteria to plant cells. S1 was expressed to high levels within 5 days of
infiltration, and Western blot analysis showed recognition of the S1 by an anti-S1 antibody.
ELISA results exhibited increased binding activity to anti-S1 with increasing concentrations of
S1, indicating their specific interaction. This ongoing study will demonstrate the potential of a
plant-produced S1 as a vaccine, therapeutic, and diagnostic tool against COVID-19 that is not
only effective, but also cost-efficient and scalable in comparison to conventional mammalian cell
culture production methods.
ContributorsNguyen, Katherine (Author) / Chen, Qiang (Thesis director) / Ghirlanda, Giovanna (Committee member) / Jugler, Collin (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12
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Description

An exploration into the history of the 1918 Influenza Pandemic and the societal impacts associated with it, as well as an analysis of the developing SARS-CoV-2 pandemic today. Based upon these analyses, similarities were drawn between the two pandemics which suggested a lack of innovation in preventative measures over the

An exploration into the history of the 1918 Influenza Pandemic and the societal impacts associated with it, as well as an analysis of the developing SARS-CoV-2 pandemic today. Based upon these analyses, similarities were drawn between the two pandemics which suggested a lack of innovation in preventative measures over the last century. Given this conclusion a series of proposals were made that should be further explored to give not only the United States, but the world at large, a better chance in the face of the next emerging disease.

ContributorsWeinman, Maya (Author) / Martin, Thomas (Thesis director) / Madhavpeddi, Adrienne (Committee member) / College of Health Solutions (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description
This thesis is a retrospective study analyzing data from patient implanted cardiac devices in order to determine the effect of SARS-CoV-2 on cardiac arrhythmias. This study is also the first, to the knowledge of the researchers, in which a cohort of undifferentiated hospitalized and non-hospitalized COVID patients were studied using

This thesis is a retrospective study analyzing data from patient implanted cardiac devices in order to determine the effect of SARS-CoV-2 on cardiac arrhythmias. This study is also the first, to the knowledge of the researchers, in which a cohort of undifferentiated hospitalized and non-hospitalized COVID patients were studied using data from cardiac implanted devices. The results from this study has shown that SARS-CoV-2 leads to statistically significant increases in arrhythmic burden, in particular increased overall arrhythmic episodes, increased VT episodes, increased AT Burden percent, and increased SVT Average Ventricular Rate, and a statistically significant decrease in VT Average Ventricular Rate.
ContributorsGomez, Mia (Author) / Ahmed, Aamina (Co-author) / Ross, Heather (Thesis director) / Kleinhans, Amy (Committee member) / Doshi, Rahul (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2022-05