Virus Diseases Commons^™

Ensemble-Based Mutational Profiling And Network Analysis Of The Sars-Cov-2 Spike Omicron Xbb Lineages For Interactions With The Ace2 Receptor And Antibodies: Cooperation Of Binding Hotspots In Mediating Epistatic Couplings Underlies Binding Mechanism And Immune Escape, Nishank Raisinghani, Mohammed Alshahrani, Grace Gupta, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we performed a computational study of binding mechanisms for the SARS-CoV-2 spike Omicron XBB lineages with the host cell receptor ACE2 and a panel of diverse class one antibodies. The central objective of this investigation was to examine the molecular factors underlying epistatic couplings among convergent evolution hotspots that enable optimal balancing of ACE2 binding and antibody evasion for Omicron variants BA.1, BA2, BA.3, BA.4/BA.5, BQ.1.1, XBB.1, XBB.1.5, and XBB.1.5 + L455F/F456L. By combining evolutionary analysis, molecular dynamics simulations, and ensemble-based mutational scanning of spike protein residues in complexes with ACE2, we identified structural stability and binding …

Covid-19 Hospital Mortality Among Patients With Invasive Mechanical Ventilation: A Comparison Between Public And Private Healthcare Services In San Luis Potosí 2020–2022, María E. Torres-Acosta, Rocío M. Cubos-Moncada, Alan Y. Martínez-Castellanos

The University of Louisville Journal of Respiratory Infections

Background: During 2019, México’s total public spending on health was 5.43% of the national gross domestic product, making it one of the countries of the Organisation for Economic Co-operation and Development that invested the least in developing public health systems. This study analyzes hospital mortality among intubated patients with laboratory-confirmed COVID-19 according to type of institution in San Luis Potosí, México, from March 18, 2020, to April 7, 2022.

Methods: This is a secondary data analysis of publicly available information about mortality among intubated patients with a laboratory-confirmed diagnosis of COVID-19 with respect to the type of hospitalization institution.

Results: …

Provider And Staff Education Surrounding Universal Hcv Screening And Linkage To Care In An Ambulatory Care Setting, Lauren Clifford

DNP Projects

Abstract

Background: In the United States, it is estimated that there are more than 2 million cases of Hepatitis C (HCV), with over 66,000 new cases since 2020 However, an estimated 75% of those with HCV go undiagnosed and less than 35% receive treatment within a year of diagnosis. In 2018, UK Healthcare (UKHC) implemented a universal HCV screening method using a Best Practice Advisory (BPA) for anyone 18 and older who presented to the Emergency Department and had labs ordered. Patients who screened positive were then referred to outpatient clinics for HCV treatment. Approximately ten percent of positive patients …

Factors Associated With Hepatitis C-Related Hospitalizations And Inpatient Mortality In The United States, Pre- And Post-Onset Of The Covid-19 Pandemic, Christina R. Samuel

College of Graduate Studies: Theses & Dissertations

Background: Hepatitis C is a significant public health problem in the United States and imposes a substantial burden on the healthcare system. Previous research shows that the COVID-19 pandemic response efforts have overshadowed hepatitis C testing and treatment measures in health care settings across the country. The purpose of this study was to describe and examine the factors associated with hepatitis C-related hospitalizations and inpatient mortality in the United States, pre- and post-onset of the COVID-19 pandemic. Methods: Data were obtained from the 2019-2020 National Inpatient Sample database. The study population included persons aged ≥18 years with hepatitis C-related inpatient …

How Individuals’ Opinions Influence Society’S Resistance To Epidemics: An Agent-Based Model Approach, Geonsik Yu, Michael J. Garee, Mario Ventresca, Yuehwern Yih

Faculty Publications

Background: Protecting public health from infectious diseases often relies on the cooperation of citizens, especially when self-care interventions are the only viable tools for disease mitigation. Accordingly, social aspects related to public opinion have been studied in the context of the recent COVID-19 pandemic. However, a comprehensive understanding of the effects of opinion-related factors on disease spread still requires further exploration. Methods: We propose an agent-based simulation framework incorporating opinion dynamics within an epidemic model based on the assumption that mass media channels play a leading role in opinion dynamics. The model simulates how opinions about preventive interventions change over …

Covid-19 Severity Among American Indians And Alaska Natives In 16 States - January 1, 2020, To March 31, 2021, Jessica Arrazola, Scott Erickson, Chiao Wen Lan, Adrian Dominguez, Sujata Joshi, Andria Apostolou, Ashley Busacker, David Casey, Christiana Coyle, Kathryn Helfrich, Jennifer Kraszewski, Thomas Kim, Genelle Lamont, Richard Leman, Pamela Lemaster, Nick Lehnertz, Mike Mannell, Dakota Matson, Alex Merrill, Tracy Miller, Benjamin Schram, Ozair Naqvi, Samantha Rice, Samantha Hyde-Rolland, Alyssa Rowell, Dean Seneca, Victoria Warren-Mears, Laura Williamson

Journal of Health Disparities Research and Practice

Objective: To compare rates and risk factors of severe COVID-19-related outcomes between American Indian/Alaska Native (AI/AN) and non-Hispanic White people (NHW).

Methods: Aggregate Social Vulnerability Index (SVI), COVID-19-related risk factor, hospitalization, and mortality data were obtained from 16 states for January 1, 2020-March 31, 2021. Generalized estimating equation Poisson regression models calculated age-adjusted cumulative incidences, incidence ratios (IR), and 95% confidence intervals (CI) comparing AI/AN and NHW persons by age, sex, and county-level SVI status.

Results: Race data were missing for 42.7% of COVID-19 cases, 24.7% of hospitalizations, and 10.1% of deaths. Risk of AI/AN COVID-19 mortality …

Long-Acting Cabotegravir And The Emergence Of Drug-Resistant Hiv, Katharine Gurski

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Integrating Spatial-Temporal Dynamics And Graph Embedding In Pde-Based Models For Predicting Covid-19 Spread, Nao Yamamoto

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Impact On The Volume Of Pathology Reports Before And During The Covid-19 Pandemic In Seer Cancer Registries, Amina Chtourou, Pamela V. Sanchez, Todd Golden, Huann Sheng Chen, Stephen M. Schwartz, Xiao Cheng Wu, Brenda Y. Hernandez, Jovanka N. Harrison, Lynne Penberthy, Serban Negoita

School of Public Health Faculty Publications

Introduction: Health care procedures including cancer screening and diagnosis were interrupted due to the COVID-19 pandemic. The extent of this impact on cancer care in the United States is not fully understood. We investigated pathology report volume as a reflection of trends in oncology services pre-pandemic and during the pandemic. Methods: Electronic pathology reports were obtained from 11 U.S. central cancer registries from NCI’s SEER Program. The reports were sorted by cancer site and document type using a validated algorithm. Joinpoint regression was used to model temporal trends from January 2018 to February 2020, project expected counts from March 2020 …

Building Up A Genomic Surveillance Platform For Sars-Cov-2 In The Middle Of A Pandemic: A True North-South Collaboration, Waqasuddin Khan, Furqan Kabir, Samiah Kanwar, Fatima Aziz, Sahrish Muneer, Adil Kalam, Mehdia Ali, Nadia Ansari, Fyezah Jehan, Muhammad Imran Nisar

Department of Paediatrics and Child Health

Next-generation sequencing technology has revolutionised pathogen surveillance over the last two decades. However, the benefits are not equitably distributed, with developing countries lagging far behind in acquiring the required technology and analytical capacity. Recent declines in the cost associated with sequencing-equipment and running consumables have created an opportunity for broader adoption. During the COVID-19 pandemic, rapid diagnostics development and DNA sequencing revolutionised the ability to diagnose and sequence SARS-CoV-2 rapidly. Socioeconomic inequalities substantially impact the ability to sequence SARS-CoV-2 strains and undermine a developing country's pandemic preparedness. Low- and middle-income countries face additional challenges in establishing, maintaining and expanding genomic …

Comparative Analysis Of Conformational Dynamics And Systematic Characterization Of Cryptic Pockets In The Sars-Cov-2 Omicron Ba.2, Ba.2.75 And Xbb.1 Spike Complexes With The Ace2 Host Receptor: Confluence Of Binding And Structural Plasticity In Mediating Networks Of Conserved Allosteric Sites, Mohammed Alshahrani, Grace Gupta, Sian Xiao, Peng Tao, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

In the current study, we explore coarse-grained simulations and atomistic molecular dynamics together with binding energetics scanning and cryptic pocket detection in a comparative examination of conformational landscapes and systematic characterization of allosteric binding sites in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB.1 spike full-length trimer complexes with the host receptor ACE2. Microsecond simulations, Markov state models and mutational scanning of binding energies of the SARS-CoV-2 BA.2 and BA.2.75 receptor binding domain complexes revealed the increased thermodynamic stabilization of the BA.2.75 variant and significant dynamic differences between these Omicron variants. Molecular simulations of the SARS-CoV-2 Omicron spike full-length trimer complexes …

Clinical Characteristics And Risk Factors For Mortality During The 'First Wave' Of Covid-19 In Reynosa, Tamaulipas, Luis G. Vargas Garcia, Francisco E. Díaz Cisneros, Antonio Gutiérrez Sierra, Juan Rosales Martínez, Manlio F. Lara Duck, Netzahualcoyotl Mayek Pérez

Research Symposium

Background: The COVID-19 pandemic has impacted public health in Mexico. As of February 2020, there have been at least four "waves" of contagion that resulted in 5.82 million positive cases and more than 325 thousand deaths. At the beginning of the COVID-19 pandemic, hospital and population-based information was available, frequently with non-specific symptoms. Little was known about the risk factors for mortality in specific conditions. We described the clinical characteristics of patients with COVID-19 in Reynosa, Tamaulipas during 2020 and identified the risk factors for mortality.

Methods: The COVID-19 cases registered from March to November 2020 in Reynosa were divided …

Exploring Conformational Landscapes And Cryptic Binding Pockets In Distinct Functional States Of The Sars-Cov-2 Omicron Ba.1 And Ba.2 Trimers: Mutation-Induced Modulation Of Protein Dynamics And Network-Guided Prediction Of Variant-Specific Allosteric Binding Sites, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

A significant body of experimental structures of SARS-CoV-2 spike trimers for the BA.1 and BA.2 variants revealed a considerable plasticity of the spike protein and the emergence of druggable binding pockets. Understanding the interplay of conformational dynamics changes induced by the Omicron variants and the identification of cryptic dynamic binding pockets in the S protein is of paramount importance as exploring broad-spectrum antiviral agents to combat the emerging variants is imperative. In the current study, we explore conformational landscapes and characterize the universe of binding pockets in multiple open and closed functional spike states of the BA.1 and BA.2 Omicron …

The Impact Of Vaccinations And Chronic Disease On Covid Death Rates, James L. Doti

Economics Faculty Articles and Research

This study presents a theoretical and empirical regression model to measure the efficacy of vaccinations in reducing COVID death rates across states over the 3/10/21 to 12/28/22 period. During that period, it was estimated that the availability of vaccinations resulted in a reduction of 427,000 COVID deaths in the nation. To arrive at that estimate, other covariants were held constant. In particular, it was found that chronic disease should be included as an explanatory variable to arrive at unbiased measures of the efficacy of vaccinations in reducing deaths. In addition, the percentage of people over the age of 65 was …

Metapopulation Dynamics Of Sars-Cov-2 Transmission In A Small-Scale Amazonian Society, Thomas Kraft, Edmond Seabright, Sarah Alami, Samuel M. Jenness, Paul L. Hooper, Bret Beheim, Helen Davis, Daniel K. Cummings, Daniel Eid Rodriguez, Maguin Gutierrez Cayuba, Emily J. Miner, Xavier De Lamballerie, Lucia Inchauste, Stéphane Priet, Benjamin Trumble, Jonathan Stieglitz, Hillard Kaplan, Michael Gurven

ESI Publications

The severity of infectious disease outbreaks is governed by patterns of human contact, which vary by geography, social organization, mobility, access to technology and healthcare, economic development, and culture. Whereas globalized societies and urban centers exhibit characteristics that can heighten vulnerability to pandemics, small-scale subsistence societies occupying remote, rural areas may be buffered. Accordingly, voluntary collective isolation has been proposed as one strategy to mitigate the impacts of COVID-19 and other pandemics on small-scale Indigenous populations with minimal access to healthcare infrastructure. To assess the vulnerability of such populations and the viability of interventions such as voluntary collective isolation, we …

Investigation Of Orthohantavirus Genetics In Rodent Reservoirs And Clinical Samples, Samuel Melvin Goodfellow

Biomedical Sciences ETDs

Orthohantaviruses are negative-sense, single stranded RNA viruses with trisegmented genomes that can cause severe disease in humans and are carried by several host reservoirs throughout the world. In the United States, Sin Nombre orthohantavirus (SNV) is the primary cause of hantavirus cardiopulmonary syndrome (HCPS) with a fatality rate of ~36% and the highest cases occuring in the southwest region. The primary SNV host reservoir is thought to be the western deer mouse, Peromyscus maniculatus, however it has been shown that other rodents can carry different orthohantaviruses. We designed a pan-orthohantavirus detection tool to survey several small mammal populations throughout New …

Neurotropic Manifestations As A Potential Risk Factor For Schizophrenia Following In Utero Exposure To Sars-Cov-2, Mir Ali R Talpur, Omar H. Elsayed, Rif S. El-Mallakh

The University of Louisville Journal of Respiratory Infections

Background: COVID-19 infection is associated with neurologic and psychiatric morbidity that suggests a direct effect of the virus or secondary effect of an inflammatory process. These neuropsychiatric consequences may increase the likelihood of schizophrenia in the offspring of women who become infected with COVID-19 during their pregnancy.

Methods: We performed a directed narrative review of the literature focusing on the proposed pathophysiological processes that lead to schizophrenia and known pathological consequences of COVID-19 infection.

Results: Schizophrenia in adult offspring has been associated with maternal infections during pregnancy by a wide range of respiratory and neurotropic pathogens. Spikes in the incidence …

Current Oral Hygiene And Recreational Behavioral Trends In Hiv Disease, Donald E. Mercante, Emily Guarisco, Elizabeth A. Lilly, Arni Rao, Kelly Treas, Clifford J. Beall, Zach Thompson, Ann L. Griffen, Eugene J. Leys, Jose A. Vazquez, Michael E. Hagensee, Paul L. Fidel

School of Dentistry Faculty Publications

Objective: HIV disease is evolving with more HIV+ persons experiencing a high quality of life with well-controlled viremia. We recently enrolled a large cohort of HIV+ and clinically relevant HIV− persons for oral microbiome analyses that included a questionnaire related to oral hygiene and recreational behaviors. Here, the questionnaire responses were analyzed for behavioral trends within the cohort, together with trends over time by comparison to a previous geographically centered HIV+ cohort. Methods: Data were collected by questionnaire at baseline visits as cross-sectional assessments. Multivariable analyses were conducted for associations of HIV status as well as age, race, and sex, …

On The Respiratory Syncytial Virus Vaccine, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.

The Impact Of The Covid-19 Pandemic On Respiratory Syncytial Virus, Amrit Kahlon, Ravina Ramnani, Kartik Rajpal, Yusra Irshad, Sudeep Chapagain, Arushee Bhatnagar, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Whole Genome Sequencing Of West Nile Viruses From Animals Submitted To The Connecticut Veterinary Medical Diagnostic Laboratory (Cvmdl), Usa, 2021, Allison Appel

Honors Scholar Theses

West Nile Virus (WNV) causes a zoonotic disease. WNV was first isolated in Uganda in 1937 and has since become an endemic in countries such as North, South, and Central America [1]. According to the Connecticut Department of Public Health, an average of 8 cases of WNV in humans have been reported since the year 2000 [2]. In this study, we focused on the genetic characterization of the viral genomic RNA of WNVs circulating in birds and mammals in the New England region. Following that aim, the complete genome sequence of two WNVs was obtained via next-generation sequencing. One sample …

Balancing Functional Tradeoffs Between Protein Stability And Ace2 Binding In The Sars-Cov-2 Omicron Ba.2, Ba.2.75 And Xbb Lineages: Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic And Energetic Changes, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Evolutionary and functional studies suggested that the emergence of the Omicron variants can be determined by multiple fitness trade-offs including the immune escape, binding affinity for ACE2, conformational plasticity, protein stability and allosteric modulation. In this study, we systematically characterize conformational dynamics, structural stability and binding affinities of the SARS-CoV-2 Spike Omicron complexes with the host receptor ACE2 for BA.2, BA.2.75, XBB.1 and XBB.1.5 variants. We combined multiscale molecular simulations and dynamic analysis of allosteric interactions together with the ensemble-based mutational scanning of the protein residues and network modeling of epistatic interactions. This multifaceted computational study characterized molecular mechanisms and …

The Effectiveness Of Examination Table Cleaning Protocols In Osteopathic Family Medicine Offices, Riley Phyu, Harrison A. Patrizio, Thomas Boyle, Todd Schachter

Rowan-Virtua Research Day

Contaminated environmental surfaces are responsible for acquisition of healthcare associated infections. In 2002 there were approximately 1.7 million healthcare associated infections, resulting in about 99,000 annual deaths. Appropriate disinfection of environmentally contaminated surfaces are required to reduce transmission of pathogens. Adenosine triphosphate (ATP) bioluminescence is being used in hospital settings to audit the cleanliness in the hospital settings. However, there is a paucity of literature in different healthcare settings outside of hospital settings. This may unintentionally result in a more relaxed cleaning protocol in outpatient settings.

Objective: To assess the effectiveness of disinfecting protocol in osteopathic family medicine offices using …

An Overview Of Viruses And The Infamous Sars-Cov-2, Jake Sun

The Confluence

Background information on viruses is first presented which include topics like evolution, ecology, history, identification, structure, and application. The novel SARS-CoV-2, which causes COVID-19, pandemic originated in Wuhan, China in December 2019. Millions of people were infected with the virus in a short time period causing urgent concern worldwide. The purpose of this review is to provide a brief and general understanding of the SARS-CoV-2 to increase awareness and actions toward preventive measures. COVID-19 is a (+) ssRNA spherical enveloped virion that causes primarily respiratory illnesses. The S protein interacts with ACE-2 receptors on the host cell to gain entry …

Identification Of Molecular Markers Associated With Copd In Non-Smokers And Smokers: A Bioinformatics Analysis, Agede O. Ayodele, Isa M. Wasagu, Ademola E. Fawibe, Alakija K. Salami

The University of Louisville Journal of Respiratory Infections

Background

Even though the proportional burden of COPD among never-smokers is significant in both developing and developed nations, accounting for around 30% of all COPD in the community, there is little awareness of the prevalence of COPD in this population. Understanding the molecular processes that underlie COPD in nonsmokers is essential.

Methods

Dataset (GSE146560) was acquired from the Gene Expression Omnibus (GEO). The limma and clusterProfiler software tools were used to identify differentially expressed genes (DEGs) and conduct a functional enrichment analysis respectively.

Results

In all, 10,583 DEGs were found, of which 1,065 were up-regulated and 9,518 were down-regulated. The …

Assessing The Impact Of Ebola Virus Inoculum Size On Likelihood Of Infection, Joseph Lukowski

Capstone Experience: Master of Public Health

Background: Indirect transmission of Ebola virus disease (EVD) is not uncommon but is poorly understood. Improving the understanding of the potential risk of EVD transmission from fomites should result in new or updated prevention or control measures for suspected or confirmed EVD cases or outbreaks.

Objective: This study aims to compile and understand pertinent data from peer-reviewed literature, establish the dose-response relationship between inoculum doses introduced to mucous membranes, and finally estimate the risk of EVD transmission from fomites.

Methods: A literature search was conducted through PubMed to obtain relevant data. This study employed this data to perform Poisson regression …

Coarse-Grained Molecular Simulations And Ensemble-Based Mutational Profiling Of Protein Stability In The Different Functional Forms Of The Sars-Cov-2 Spike Trimers: Balancing Stability And Adaptability In Ba.1, Ba.2 And Ba.2.75 Variants, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Evolutionary and functional studies have suggested that the emergence of Omicron variants can be determined by multiple fitness tradeoffs including immune escape, binding affinity, conformational plasticity, protein stability, and allosteric modulation. In this study, we embarked on a systematic comparative analysis of the conformational dynamics, electrostatics, protein stability, and allostery in the different functional states of spike trimers for BA.1, BA.2, and BA.2.75 variants. Using efficient and accurate coarse-grained simulations and atomistic reconstruction of the ensembles, we examined the conformational dynamics of the spike trimers that agree with the recent functional studies, suggesting that BA.2.75 trimers are the most stable …

Intergenerational Change In Hiv/Aids-Related Stigma In Cato Manor, Mijin Cho

Independent Study Project (ISP) Collection

In South Africa, the world’s epicenter of the HIV/AIDS pandemic, HIV-related stigma and stigma-enforcing stereotypes continue to serve as major health barriers to receiving adequate HIV prevention and treatment. While there continues to be a rise in research and advocacy, there is a need to study HIV stigma through a multigenerational lens that addresses the changing HIV/AIDS stigma in the post-apartheid era. Using qualitative methodology, this study aims to explore the generational differences in perceived HIV stigma between females in their 20s and above 50 years of age (as denoted by “50s+”) living in Cato Manor, South Africa. The study …

Virtual And In Vitro Screening Of Natural Products Identifies Indole And Benzene Derivatives As Inhibitors Of Sars-Cov-2 Main Protease (MPro), Dony Ang, Riley Kendall, Hagop S. Atamian

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The rapid spread of the coronavirus disease 2019 (COVID-19) resulted in serious health, social, and economic consequences. While the development of effective vaccines substantially reduced the severity of symptoms and the associated deaths, we still urgently need effective drugs to further reduce the number of casualties associated with SARS-CoV-2 infections. Machine learning methods both improved and sped up all the different stages of the drug discovery processes by performing complex analyses with enormous datasets. Natural products (NPs) have been used for treating diseases and infections for thousands of years and represent a valuable resource for drug discovery when combined with …

Disease Risk Of Reintroducing Primates Confiscated From The Illegal Wildlife Trade, Ana Patricia Mendoza Becerra

Dissertations

Zoonotic infections are easily shared between human and other primates, and thus primate trafficking poses a high risk of introducing zoonotic pathogens into urban environments as well as spreading human-associated diseases into natural environments when infected primates are released. The magnitude of these risks has not been thoroughly studied in the context of primate trafficking and rehabilitation of Neotropical primates. In this dissertation, I address some knowledge gaps in disease risk analysis of reintroducing trafficked primates. In chapter 1, I describe the dynamics, diversity, and composition of live wildlife trafficking in urban markets in Peru. I found these markets are …