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SARS-CoV-2

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Gain-Of-Signal Assays For Probing Inhibition Of Sars-Cov-2 Mpro/3clpro In Living Cells, Seyed Arad Moghadasi, Morgan A Esler, Yuka Otsuka, Jordan T Becker, Sofia N Moraes, Constance B Anderson, Srinivas Chamakuri, Christopher Belica, Chloe Wick, Daniel A Harki, Damian W Young, Louis Scampavia, Timothy P Spicer, Ke Shi, Hideki Aihara, William L Brown, Reuben S Harris Jun 2022

Gain-Of-Signal Assays For Probing Inhibition Of Sars-Cov-2 Mpro/3clpro In Living Cells, Seyed Arad Moghadasi, Morgan A Esler, Yuka Otsuka, Jordan T Becker, Sofia N Moraes, Constance B Anderson, Srinivas Chamakuri, Christopher Belica, Chloe Wick, Daniel A Harki, Damian W Young, Louis Scampavia, Timothy P Spicer, Ke Shi, Hideki Aihara, William L Brown, Reuben S Harris

Faculty, Staff and Students Publications

The main protease, Mpro, of SARS-CoV-2 is required to cleave the viral polyprotein into precise functional units for virus replication and pathogenesis. Here, we report quantitative reporters for Mpro function in living cells in which protease inhibition by genetic or chemical methods results in robust signal readouts by fluorescence (enhanced green fluorescent protein [eGFP]) or bioluminescence (firefly luciferase). These gain-of-signal systems are scalable to high-throughput platforms for quantitative discrimination between Mpro mutants and/or inhibitor potencies as evidenced by validation of several reported inhibitors. Additional utility is shown by single Mpro amino acid variants and structural information combining to demonstrate that …


Treating Cytokine Storm In Patients With Covid-19, Ahmed Abdelhaleem, Deekshitha Turaka, Shameera Shaik Masthan, Steven B Lippmann Jun 2022

Treating Cytokine Storm In Patients With Covid-19, Ahmed Abdelhaleem, Deekshitha Turaka, Shameera Shaik Masthan, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.


Biochemical, Biophysical, And Immunological Characterization Of Respiratory Secretions In Severe Sars-Cov-2 Infections, Michael J Kratochvil, Gernot Kaber, Sally Demirdjian, Pamela C Cai, Elizabeth B Burgener, Nadine Nagy, Graham L Barlow, Medeea Popescu, Mark R Nicolls, Michael G Ozawa, Donald P Regula, Ana E Pacheco-Navarro, Samuel Yang, Vinicio A De Jesus Perez, Harry Karmouty-Quintana, Andrew M Peters, Bihong Zhao, Maximilian L Buja, Pamela Y Johnson, Robert B Vernon, Thomas N Wight, Carlos E Milla, Angela J Rogers, Andrew J Spakowitz, Sarah C Heilshorn, Paul L Bollyky Jun 2022

Biochemical, Biophysical, And Immunological Characterization Of Respiratory Secretions In Severe Sars-Cov-2 Infections, Michael J Kratochvil, Gernot Kaber, Sally Demirdjian, Pamela C Cai, Elizabeth B Burgener, Nadine Nagy, Graham L Barlow, Medeea Popescu, Mark R Nicolls, Michael G Ozawa, Donald P Regula, Ana E Pacheco-Navarro, Samuel Yang, Vinicio A De Jesus Perez, Harry Karmouty-Quintana, Andrew M Peters, Bihong Zhao, Maximilian L Buja, Pamela Y Johnson, Robert B Vernon, Thomas N Wight, Carlos E Milla, Angela J Rogers, Andrew J Spakowitz, Sarah C Heilshorn, Paul L Bollyky

Faculty, Staff and Student Publications

Thick, viscous respiratory secretions are a major pathogenic feature of COVID-19, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e., resistance to flow) of respiratory secretions collected from intubated COVID-19 patients. We found the percentages of solids and protein content were greatly elevated in COVID-19 compared with heathy control samples and closely resembled levels seen in cystic fibrosis, a genetic disease known for thick, tenacious respiratory secretions. DNA and hyaluronan (HA) were major components of respiratory secretions in COVID-19 and were likewise abundant in cadaveric lung tissues from these …


Symptomatic, Clinical And Biomarker Associations For Mortality In Hospitalized Covid-19 Patients Enriched For African Americans, Hassan Ashktorab, Antonio Pizuorno, Folake Adeleye, Adeyinka Laiyemo, Maryam Mehdipour Dalivand, Farshad Aduli, Zaki A Sherif, Gholamreza Oskrochi, Kibreab Angesom, Philip Oppong-Twene, Suryanarayana Reddy Challa, Nnaemeka Okorie, Esther S Moon, Edward Romos, Boubini Jones-Wonni, Abdoul Madjid Kone, Sheldon Rankine, Camelita Thrift, Derek Scholes, Chiamaka Ekwunazu, Abigail Banson, Brianna Mitchell, Guttu Maskalo, Jillian Ross, Julencia Curtis, Rachel Kim, Chandler Gilliard, Geetha Ahuja, Joseph Mathew, Warren Gavin, Areeba Kara, Manuel Hache-Marliere, Leonidas Palaiodimos, Vishnu R. Mani, Aleksandr Kalabin, Vijay Reddy Gayam, Pavani Reddy Garlapati, Joseph B. Miller Md, Lakshmi Gayathri Chirumamilla, Fatimah Jackson, John M. Carethers, Farin Kamangar, Hassan Brim Jun 2022

Symptomatic, Clinical And Biomarker Associations For Mortality In Hospitalized Covid-19 Patients Enriched For African Americans, Hassan Ashktorab, Antonio Pizuorno, Folake Adeleye, Adeyinka Laiyemo, Maryam Mehdipour Dalivand, Farshad Aduli, Zaki A Sherif, Gholamreza Oskrochi, Kibreab Angesom, Philip Oppong-Twene, Suryanarayana Reddy Challa, Nnaemeka Okorie, Esther S Moon, Edward Romos, Boubini Jones-Wonni, Abdoul Madjid Kone, Sheldon Rankine, Camelita Thrift, Derek Scholes, Chiamaka Ekwunazu, Abigail Banson, Brianna Mitchell, Guttu Maskalo, Jillian Ross, Julencia Curtis, Rachel Kim, Chandler Gilliard, Geetha Ahuja, Joseph Mathew, Warren Gavin, Areeba Kara, Manuel Hache-Marliere, Leonidas Palaiodimos, Vishnu R. Mani, Aleksandr Kalabin, Vijay Reddy Gayam, Pavani Reddy Garlapati, Joseph B. Miller Md, Lakshmi Gayathri Chirumamilla, Fatimah Jackson, John M. Carethers, Farin Kamangar, Hassan Brim

Emergency Medicine Articles

BACKGROUND AND AIMS: Initial reports on US COVID-19 showed different outcomes in different races. In this study we use a diverse large cohort of hospitalized COVID-19 patients to determine predictors of mortality.

METHODS: We analyzed data from hospitalized COVID-19 patients (n = 5852) between March 2020- August 2020 from 8 hospitals across the US. Demographics, comorbidities, symptoms and laboratory data were collected.

RESULTS: The cohort contained 3,662 (61.7%) African Americans (AA), 286 (5%) American Latinx (LAT), 1,407 (23.9%), European Americans (EA), and 93 (1.5%) American Asians (AS). Survivors and non-survivors mean ages in years were 58 and 68 for AA, …


Humidity Reduces Rapid And Distant Airborne Dispersal Of Viable Viral Particles In Classroom Settings, Antun Skanata, Fabrizio Spagnolo, Molly Metz, Davida S. Smyth, John J. Dennehy Jun 2022

Humidity Reduces Rapid And Distant Airborne Dispersal Of Viable Viral Particles In Classroom Settings, Antun Skanata, Fabrizio Spagnolo, Molly Metz, Davida S. Smyth, John J. Dennehy

Biology Faculty Publications (Archived)

The transmission of airborne pathogens is considered to be the main route through which a number of known and emerging respiratory diseases infect their hosts. While physical distancing and mask wearing may help mitigate short-range transmission, the extent of long-range transmission in closed spaces where a pathogen remains suspended in the air remains unknown. We have developed a method to detect viable virus particles by using an aerosolized bacteriophage Phi6 in combination with its host Pseudomonas phaseolicola, which when seeded on agar plates acts as a virus detector that can be placed at a range of distances away from …


Orally Delivered Perilla (Perilla Frutescens) Leaf Extract Effectively Inhibits Sars-Cov-2 Infection In A Syrian Hamster Model, Yuan-Fan Chin, Wen-Fan Tang, Yu-Hsiu Chang, Tein-Yao Chang, Wen-Chin Lin, Chia-Yi Lin, Chuen-Mi Yang, Hsueh-Ling Wu, Ping-Cheng Li, Jun-Ren Sun, Shu-Chen Hsu, Chia-Ying Lee, Hsuan-Ying Lu, Jia-Yu Chang, Jia-Rong Jheng, Cheng Cheung Chen, Jyh-Hwa Kau, Chih-Heng Huang, Cheng-Hsun Chiu, Yi-Jen Hung, Hui-Ping Tsai, Jim-Tong Horng Jun 2022

Orally Delivered Perilla (Perilla Frutescens) Leaf Extract Effectively Inhibits Sars-Cov-2 Infection In A Syrian Hamster Model, Yuan-Fan Chin, Wen-Fan Tang, Yu-Hsiu Chang, Tein-Yao Chang, Wen-Chin Lin, Chia-Yi Lin, Chuen-Mi Yang, Hsueh-Ling Wu, Ping-Cheng Li, Jun-Ren Sun, Shu-Chen Hsu, Chia-Ying Lee, Hsuan-Ying Lu, Jia-Yu Chang, Jia-Rong Jheng, Cheng Cheung Chen, Jyh-Hwa Kau, Chih-Heng Huang, Cheng-Hsun Chiu, Yi-Jen Hung, Hui-Ping Tsai, Jim-Tong Horng

Journal of Food and Drug Analysis

On analyzing the results of cell-based assays, we have previously shown that perilla (Perilla frutescens) leaf extract (PLE), a food supplement and orally deliverable traditional Chinese medicine approved by the Taiwan Food and Drug Administration, effectively inhibits SARS-CoV-2 by directly targeting virions. PLE was also found to modulate virus-induced cytokine expression levels. In this study, we explored the anti-SARS-CoV-2 activity of PLE in a hamster model by examining viral loads and virus-induced immunopathology in lung tissues. Experimental animals were intranasally challenged with different SARS-CoV-2 doses. Jugular blood samples and lung tissue specimens were obtained in the acute disease stage (3−4 …


Analysis Of Blood Type For Sars-Cov-2 And Correlation For Disease Acquisition In Various Sociodemographic Groups Including Women Of Childbearing Age., Maria L. Vacca, Nikunj Vyas, Joshua Banks, Elaine Joyce, Cindy Hou, Benjamin E. Leiby, Stefanie Deangelo, Todd P. Levin, Autum Shingler-Nace, Marilyn Mapp, Ashlee Hiester, Jonathan H. Coughenour Jun 2022

Analysis Of Blood Type For Sars-Cov-2 And Correlation For Disease Acquisition In Various Sociodemographic Groups Including Women Of Childbearing Age., Maria L. Vacca, Nikunj Vyas, Joshua Banks, Elaine Joyce, Cindy Hou, Benjamin E. Leiby, Stefanie Deangelo, Todd P. Levin, Autum Shingler-Nace, Marilyn Mapp, Ashlee Hiester, Jonathan H. Coughenour

Division of Infectious Diseases and Environmental Medicine Faculty Papers

BACKGROUND: Multiple studies have occurred to determine if a patient's blood type, Rhesus factor (Rh), and sociodemographic attributes contribute to contracting SARS-CoV-2. True association remains unknown.

METHODS: Inclusion criteria included in-patients who were tested for SARS-CoV-2 with blood type assessed. Study endpoints combined ABO, Rh and all-cause inpatient mortality (ACIM) with testing positivity. Pregnancy status was one of several secondary endpoints evaluated. A logistic regression analysis was used to estimate association.

RESULTS: Of the 27,662 patients who met inclusion criteria, Type A blood was associated with increased positivity [1.01 (1.0-1.21), P = .03]. Type B [1.10 (0.99-1.23), P = .08] …


Genomic Insights Into Mechanisms Of Microbial Evolution And Evolution-Inspired Strategies To Combat Pathogen Diversity, Saymon Akther Jun 2022

Genomic Insights Into Mechanisms Of Microbial Evolution And Evolution-Inspired Strategies To Combat Pathogen Diversity, Saymon Akther

Dissertations, Theses, and Capstone Projects

We live in an era of emerging infectious diseases that are increasingly common, rapidly spreading, and gravely devastating. Lyme disease, caused by bacteria belonging to the genus Borreliella, is rapidly rising in the Northern Hemisphere because of geographic range expansion of both the tick vectors and the pathogens. Evolutionary comparative analysis of Borreliella genomes is a key to understanding the phylogeographic history and mechanisms of their global diversification. Moreover, genomic variations in Borreliella associated with human pathogenicity, e.g., at loci encoding cell-surface antigens interacting with the vertebrate hosts, have not been fully identified. Similarly, the ongoing COVID-19 pandemic, caused …


Rationale Of Using The Dual Chemokine Receptor Ccr2/Ccr5 Inhibitor Cenicriviroc For The Treatment Of Covid-19, Daniel Clark Files, Frank Tacke, Alexandra O'Sullivan, Patrick Dorr, William G. Ferguson, William G. Powderly Jun 2022

Rationale Of Using The Dual Chemokine Receptor Ccr2/Ccr5 Inhibitor Cenicriviroc For The Treatment Of Covid-19, Daniel Clark Files, Frank Tacke, Alexandra O'Sullivan, Patrick Dorr, William G. Ferguson, William G. Powderly

2020-Current year OA Pubs

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has created a global pandemic infecting over 230 million people and costing millions of lives. Therapies to attenuate severe disease are desperately needed. Cenicriviroc (CVC), a C-C chemokine receptor type 5 (CCR5) and C-C chemokine receptor type 2 (CCR2) antagonist, an agent previously studied in advanced clinical trials for patients with HIV or nonalcoholic steatohepatitis (NASH), may have the potential to reduce respiratory and cardiovascular organ failures related to COVID-19. Inhibiting the CCR2 and CCR5 pathways could attenuate or prevent inflammation or fibrosis in both early and …


Cross-Reactive Immunity Against The Sars-Cov-2 Omicron Variant Is Low In Pediatric Patients With Prior Covid-19 Or Mis-C., Juanjie Tang, Tanya Novak, Julian Hecker, Gabrielle Grubbs, Fatema Tuz Zahra, Lorenza Bellusci, Sara Pourhashemi, Janet Chou, Kristin Moffitt, Natasha B. Halasa, Stephanie P. Schwartz, Tracie C. Walker, Keiko M. Tarquinio, Matt S. Zinter, Mary A. Staat, Shira J. Gertz, Natalie Z. Cvijanovich, Jennifer E. Schuster, Laura L. Loftis, Bria M. Coates, Elizabeth H. Mack, Katherine Irby, Julie C. Fitzgerald, Courtney M. Rowan, Michele Kong, Heidi R. Flori, Aline B. Maddux, Steven L. Shein, Hillary Crandall, Janet R. Hume, Charlotte V. Hobbs, Adriana H. Tremoulet, Chisato Shimizu, Jane C. Burns, Sabrina R. Chen, Hye Kyung Moon, Christoph Lange, Adrienne G. Randolph, Surender Khurana May 2022

Cross-Reactive Immunity Against The Sars-Cov-2 Omicron Variant Is Low In Pediatric Patients With Prior Covid-19 Or Mis-C., Juanjie Tang, Tanya Novak, Julian Hecker, Gabrielle Grubbs, Fatema Tuz Zahra, Lorenza Bellusci, Sara Pourhashemi, Janet Chou, Kristin Moffitt, Natasha B. Halasa, Stephanie P. Schwartz, Tracie C. Walker, Keiko M. Tarquinio, Matt S. Zinter, Mary A. Staat, Shira J. Gertz, Natalie Z. Cvijanovich, Jennifer E. Schuster, Laura L. Loftis, Bria M. Coates, Elizabeth H. Mack, Katherine Irby, Julie C. Fitzgerald, Courtney M. Rowan, Michele Kong, Heidi R. Flori, Aline B. Maddux, Steven L. Shein, Hillary Crandall, Janet R. Hume, Charlotte V. Hobbs, Adriana H. Tremoulet, Chisato Shimizu, Jane C. Burns, Sabrina R. Chen, Hye Kyung Moon, Christoph Lange, Adrienne G. Randolph, Surender Khurana

Manuscripts, Articles, Book Chapters and Other Papers

Neutralization capacity of antibodies against Omicron after a prior SARS-CoV-2 infection in children and adolescents is not well studied. Therefore, we evaluated virus-neutralizing capacity against SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants by age-stratified analyses (5 years of age. As expected, convalescent pediatric COVID-19 and MIS-C cohorts demonstrate higher neutralization titers than hospitalized acute COVID-19 patients. Overall, children and adolescents show some loss of cross-neutralization against all variants, with the most pronounced loss against Omicron. In contrast to SARS-CoV-2 infection, children vaccinated twice demonstrated higher titers against Alpha, Beta, Gamma, Delta and Omicron. These findings can influence transmission, re-infection …


Evaluation Of Mrna-1273 Covid-19 Vaccine In Children 6 To 11 Years Of Age, C Buddy Creech, Evan Anderson, Vladimir Berthaud, Inci Yildirim, Andrew M. Atz, Ivan Melendez Baez, Daniel Finkelstein, Paul Pickrell, Judith Kirstein, Clifford Yut, Ronald Blair, Robert A. Clifford, Michael Dunn, James D. Campbell, David C. Montefiori, Joanne E. Tomassini, Xiaoping Zhao, Weiping Deng, Honghong Zhou, Daniela Ramirez Schrempp, Kelly Hautzinger, Bethany Girard, Karen Slobod, Roderick Mcphee, Rolando Pajon, Rituparna Das, Jacqueline M. Miller, Sabine Schnyder Ghamloush, Walter N. Dehority, Kidcove Study Group May 2022

Evaluation Of Mrna-1273 Covid-19 Vaccine In Children 6 To 11 Years Of Age, C Buddy Creech, Evan Anderson, Vladimir Berthaud, Inci Yildirim, Andrew M. Atz, Ivan Melendez Baez, Daniel Finkelstein, Paul Pickrell, Judith Kirstein, Clifford Yut, Ronald Blair, Robert A. Clifford, Michael Dunn, James D. Campbell, David C. Montefiori, Joanne E. Tomassini, Xiaoping Zhao, Weiping Deng, Honghong Zhou, Daniela Ramirez Schrempp, Kelly Hautzinger, Bethany Girard, Karen Slobod, Roderick Mcphee, Rolando Pajon, Rituparna Das, Jacqueline M. Miller, Sabine Schnyder Ghamloush, Walter N. Dehority, Kidcove Study Group

Pediatrics Research and Scholarship

BACKGROUND: Vaccination of children to prevent coronavirus disease 2019 (Covid-19) is an urgent public health need. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in children 6 to 11 years of age are unknown.

METHODS: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled expansion evaluation of the selected dose. In part 2, we randomly assigned children (6 to 11 years of age) in a 3:1 ratio to receive two injections of mRNA-1273 (50 μg each) or placebo, administered 28 days apart. The primary objectives were evaluation of …


Multivalent Designed Proteins Neutralize Sars-Cov-2 Variants Of Concern And Confer Protection Against Infection In Mice, Andrew C Hunt, James Brett Case, Rita E Chen, Baoling Ying, Adam L Bailey, Natasha M Kafai, Michael S Diamond, Et Al May 2022

Multivalent Designed Proteins Neutralize Sars-Cov-2 Variants Of Concern And Confer Protection Against Infection In Mice, Andrew C Hunt, James Brett Case, Rita E Chen, Baoling Ying, Adam L Bailey, Natasha M Kafai, Michael S Diamond, Et Al

Open Access Publications

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise and prolong the coronavirus disease 2019 (COVID-19) pandemic. Here, we used a cell-free expression workflow to rapidly screen and optimize constructs containing multiple computationally designed miniprotein inhibitors of SARS-CoV-2. We found the broadest efficacy was achieved with a homotrimeric version of the 75-residue angiotensin-converting enzyme 2 (ACE2) mimic AHB2 (TRI2-2) designed to geometrically match the trimeric spike architecture. Consistent with the design model, in the cryo-electron microscopy structure TRI2-2 forms a tripod at the apex of the spike protein that engaged all three receptor binding domains simultaneously. …


Transmission Risk Of Covid-19 In High School And College Water Polo, Raymond J Kreienkamp, Christopher J Kreienkamp, Cindy Terrill, Mark E Halstead, Jason G Newland May 2022

Transmission Risk Of Covid-19 In High School And College Water Polo, Raymond J Kreienkamp, Christopher J Kreienkamp, Cindy Terrill, Mark E Halstead, Jason G Newland

2020-Current year OA Pubs

BACKGROUND: Concerns that athletes may be at a higher risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has led to reduced participation in sports during the COVID-19 pandemic. We aimed to assess COVID-19 incidence and transmission during the spring 2021 high school and college water polo seasons across the United States.

METHODS: This prospective observational study enrolled 1825 water polo athletes from 54 high schools and 36 colleges. Surveys were sent to coaches throughout the season, and survey data were collected and analyzed.

RESULTS: We identified 17 COVID-19 cases among 1223 high school water polo athletes (1.4%) and …


Novel Mobility Index Tracks Covid-19 Transmission Following Stay-At-Home Orders, Peter Hyunwuk Her, Sahar Saeed, Khai Hoan Tram, Sahir R Bhatnagar May 2022

Novel Mobility Index Tracks Covid-19 Transmission Following Stay-At-Home Orders, Peter Hyunwuk Her, Sahar Saeed, Khai Hoan Tram, Sahir R Bhatnagar

Open Access Publications

Considering the emergence of SARS-CoV-2 variants and low vaccine access and uptake, minimizing human interactions remains an effective strategy to mitigate the spread of SARS-CoV-2. Using a functional principal component analysis, we created a multidimensional mobility index (MI) using six metrics compiled by SafeGraph from all counties in Illinois, Ohio, Michigan and Indiana between January 1 to December 8, 2020. Changes in mobility were defined as a time-updated 7-day rolling average. Associations between our MI and COVID-19 cases were estimated using a quasi-Poisson hierarchical generalized additive model adjusted for population density and the COVID-19 Community Vulnerability Index. Individual mobility metrics …


Th1, Th2, And Th17 Inflammatory Pathways Predict Cardiometabolic Protein Expression In Serum Of Covid-19 Patients, James Richard Michels May 2022

Th1, Th2, And Th17 Inflammatory Pathways Predict Cardiometabolic Protein Expression In Serum Of Covid-19 Patients, James Richard Michels

Honors Theses

A predominant source of complications in SARS-CoV-2 patients arises from severe systemic inflammation contributed to by Helper T-cell associated cytokines, potentially leading to tissue damage and organ failure. The high inflammatory burden of this viral infection often results in cardiovascular comorbidities. A better understanding of the interaction between the cytokine storm and cardiovascular proteins might inform medical decisions and therapeutic approaches. We hypothesized that all major helper T-cell inflammatory pathways (Helper T 1, Helper T 2 and Helper T 17) synergistically contribute to cardiometabolic pathways in serum of COVID-19 patients, and that both of these factors correlate to COVID-19 severity. …


Innate Immunity In The Pathobiology And Treatment Of Infectious And Neurodegenerative Diseases, Mai Mostafa May 2022

Innate Immunity In The Pathobiology And Treatment Of Infectious And Neurodegenerative Diseases, Mai Mostafa

Theses & Dissertations

Mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells) are the governors of innate immunity which is the body’s first line of defense against microbial pathogens. They act beneficial or detrimental. They are crucial for an effective non-specific immune response to invading pathogens by engulfing, destroying, then eliciting an adaptive specific immune response. Given their pivotal functions in the host immune defense, studying MP immune responses in disease is paramount important for understanding disease pathobiology and uncovering therapeutic strategies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the driver of acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) amongst …


Covid-19, Vaccination, And Heart Transplantation, Forest W. Arnold May 2022

Covid-19, Vaccination, And Heart Transplantation, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.


Discovery Of Ojt010 As A Novel Inhibitor Of Severe Acute Respiratory Syndrome Coronavirus 2, Manvir Kaur May 2022

Discovery Of Ojt010 As A Novel Inhibitor Of Severe Acute Respiratory Syndrome Coronavirus 2, Manvir Kaur

Dissertations (2016-Present)

The current pandemic of coronavirus disease (COVID-19) caused by the highly infectious pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents a global public health challenge. The emergence of deadly SARS-CoV-2 variants with mutations on the viral genes has made it more imperative to discover therapeutics that target the host receptors for COVID-19 treatment. Therefore, our research has targeted the critical host entry receptors: Angiotensin-converting enzyme-2 (ACE2) for SARS-CoV-2 entry into the human cells. SARS-CoV-2 is an enveloped RNA beta coronavirus that infects human cells via interaction with the ACE2 receptor, followed by viral replication and virus dissemination. Spike protein …


How Do I Implement An Outpatient Program For The Administration Of Convalescent Plasma For Covid-19, Evan M. Bloch, Aaron A R Tobian, Shmuel Shoham, Daniel F. Hanley, Thomas J. Gniadek, Edward R. Cachay, Barry R. Meisenberg, Kimberly Kafka, Christi Marshall, Sonya L. Heath, Aarthi Shenoy, James H. Paxton, Adam Levine, Donald Forthal, Yuriko Fukuta, Moises A. Huaman, Alyssa Ziman, Jill Adamski, Jonathan Gerber, Daniel Cruser, Seble G. Kassaye, Giselle S. Mosnaim, Bela Patel, Ryan A. Metcalf, Shweta Anjan, Ronald B. Reisler, Anusha Yarava, Karen Lane, Nichol Mcbee, Amy Gawad, Jay S. Raval, Martin Zand, Matthew Abinante, Patrick B. Broderick, Arturo Casadevall, David Sullivan, Kelly A. Gebo May 2022

How Do I Implement An Outpatient Program For The Administration Of Convalescent Plasma For Covid-19, Evan M. Bloch, Aaron A R Tobian, Shmuel Shoham, Daniel F. Hanley, Thomas J. Gniadek, Edward R. Cachay, Barry R. Meisenberg, Kimberly Kafka, Christi Marshall, Sonya L. Heath, Aarthi Shenoy, James H. Paxton, Adam Levine, Donald Forthal, Yuriko Fukuta, Moises A. Huaman, Alyssa Ziman, Jill Adamski, Jonathan Gerber, Daniel Cruser, Seble G. Kassaye, Giselle S. Mosnaim, Bela Patel, Ryan A. Metcalf, Shweta Anjan, Ronald B. Reisler, Anusha Yarava, Karen Lane, Nichol Mcbee, Amy Gawad, Jay S. Raval, Martin Zand, Matthew Abinante, Patrick B. Broderick, Arturo Casadevall, David Sullivan, Kelly A. Gebo

Pathology Research and Scholarship

Convalescent plasma, collected from donors who have recovered from a pathogen of interest, has been used to treat infectious diseases, particularly in times of outbreak, when alternative therapies were unavailable. The COVID-19 pandemic revived interest in the use of convalescent plasma. Large observational studies and clinical trials that were executed during the pandemic provided insight into how to use convalescent plasma, whereby high levels of antibodies against the pathogen of interest and administration early within the time course of the disease are critical for optimal therapeutic effect. Several studies have shown outpatient administration of COVID-19 convalescent plasma (CCP) to be …


Spike Protein Structural Dynamics Of Sars-Cov-2 Coronaviruses Studied Using Molecular Dynamics, William Strickland May 2022

Spike Protein Structural Dynamics Of Sars-Cov-2 Coronaviruses Studied Using Molecular Dynamics, William Strickland

Biological Sciences Undergraduate Honors Theses

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has overwhelmingly impacted the global population, accounting for millions of confirmed infections and deaths over the last year. The virus’s influence on the health and safety of individuals, the economy, and daily life has been disruptive and devastating. While SARS-CoV-2 and SARS-CoV-1, two closely related members of the SARS coronaviruses, have shown the ability to cross the species barrier and infect humans, SARS-CoV-2 has predominantly been the virus responsible for the number of infections presently known. SARS-CoV-2 has also proven to be volatile, as many variants have …


Covid-19 In Lebanon: Demographics And Distribution, Mahdi Fadlallah, Fadi Hobeiche, Marie Therese Jamal, Elie Salem-Sokhn Apr 2022

Covid-19 In Lebanon: Demographics And Distribution, Mahdi Fadlallah, Fadi Hobeiche, Marie Therese Jamal, Elie Salem-Sokhn

BAU Journal - Health and Wellbeing

COVID-19 pandemic has emerged over more than 200 countries leading to more than 117 million infection cases and more than 2.6 million deaths. Lebanon is one of the countries affected by this disease especially in the second half of 2020 reaching its peak early this year. In this study, we studied the impact of multiple factors on this surge and analyzed the positive tests among different age groups over a period of one year (from March 2020 to February 2021). Data was collected from one medical center in Beirut where more than 20,000 PCR tests were done using RT-PCR method …


Thermodynamically Coupled Biosensors For Detecting Neutralizing Antibodies Against Sars-Cov-2 Variants, Jason Z Zhang, Laura A Vanblargan, Michael S Diamond, Et Al. Apr 2022

Thermodynamically Coupled Biosensors For Detecting Neutralizing Antibodies Against Sars-Cov-2 Variants, Jason Z Zhang, Laura A Vanblargan, Michael S Diamond, Et Al.

2020-Current year OA Pubs

We designed a protein biosensor that uses thermodynamic coupling for sensitive and rapid detection of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in serum. The biosensor is a switchable, caged luciferase-receptor-binding domain (RBD) construct that detects serum-antibody interference with the binding of virus RBD to angiotensin-converting enzyme 2 (ACE-2) as a proxy for neutralization. Our coupling approach does not require target modification and can better distinguish sample-to-sample differences in analyte binding affinity and abundance than traditional competition-based assays.


Passive Sampling To Scale Wastewater Surveillance Of Infectious Disease: Lessons Learned From Covid-19, Aaron Bivins, Devrim Kaya, Warish Ahmed, Joe Brown, Caitlyn Butler, Justin Greaves, Reann Leal, Kendra Maas, Gouthami Rao, Samendra Sherchan, Deborah Sills, Ryan Sinclair, Robert T. Wheeler, Cresten Mansfeldt Apr 2022

Passive Sampling To Scale Wastewater Surveillance Of Infectious Disease: Lessons Learned From Covid-19, Aaron Bivins, Devrim Kaya, Warish Ahmed, Joe Brown, Caitlyn Butler, Justin Greaves, Reann Leal, Kendra Maas, Gouthami Rao, Samendra Sherchan, Deborah Sills, Ryan Sinclair, Robert T. Wheeler, Cresten Mansfeldt

Faculty Journal Articles

Much of what is known and theorized concerning passive sampling techniques has been developed considering chemical analytes. Yet, historically, biological analytes, such as Salmonella typhi, have been collected from wastewater via passive sampling with Moore swabs. In response to the COVID-19 pandemic, passive sampling is re-emerging as a promising technique to monitor SARS-CoV-2 RNA in wastewater. Method comparisons and disease surveillance using composite, grab, and passive sampling for SARS-CoV-2 RNA detection have found passive sampling with a variety of materials routinely produced qualitative results superior to grab samples and useful for sub-sewershed surveillance of COVID-19. Among individual studies, SARS-CoV-2 RNA …


Are Antipyretic Medications Compatible With Sars-Cov-2 Vaccines?, Sharanya S E Santhi, Niguma Rayamajhi, Steven B Lippmann Apr 2022

Are Antipyretic Medications Compatible With Sars-Cov-2 Vaccines?, Sharanya S E Santhi, Niguma Rayamajhi, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.


Clinical Characteristics, Risk Factors, And Outcomes Among A Large Midwestern U.S. Cohort Of Patients Hospitalized With Covid-19 Prior To Vaccine Availability, Viviana Zlochiver, Ana Cristina Perez Moreno, Michael Peterson, Khalil Odeh, Ashley Mainville, Katherine Busniewski, Jon Wrobel, Mohamed Hommeida, Blair Tilkens, Payal Sharma, Hlu Vang, Sara Walczak, Fekadesilassie Moges, Kritika Garg, A. Jamil Tajik, Suhail Q. Allaqaband, Tanvir Bajwa, M. Fuad Jan Apr 2022

Clinical Characteristics, Risk Factors, And Outcomes Among A Large Midwestern U.S. Cohort Of Patients Hospitalized With Covid-19 Prior To Vaccine Availability, Viviana Zlochiver, Ana Cristina Perez Moreno, Michael Peterson, Khalil Odeh, Ashley Mainville, Katherine Busniewski, Jon Wrobel, Mohamed Hommeida, Blair Tilkens, Payal Sharma, Hlu Vang, Sara Walczak, Fekadesilassie Moges, Kritika Garg, A. Jamil Tajik, Suhail Q. Allaqaband, Tanvir Bajwa, M. Fuad Jan

Journal of Patient-Centered Research and Reviews

Purpose: The COVID-19 pandemic posed unprecedented demands on health care. This study aimed to characterize COVID-19 inpatients and examine trends and risk factors associated with hospitalization duration, intensive care unit (ICU) admission, and in-hospital mortality.

Methods: This retrospective study analyzed patients with SARS-CoV-2 infection hospitalized at an integrated health system between February 2, 2020, and December 12, 2020. Patient characteristics and clinical outcomes were obtained from medical records. Backward stepwise logistic regression analyses were used to identify independent risk factors of ICU admission and in-hospital mortality. Cox proportional hazards models were used to evaluate relationships between ICU admission and in-hospital …


Laboratory Findings In Covid-19 - Alterations Of Hematological, Immunological, Biochemical, Hormonal And Other Lab Panels: A Narrative Review, Yousef Rasmi, Lucas Paulo Jacinto Saavedra, Matei-Alexandru Cozma, Heba El-Nashar, Shaza Aly, Nouran Fahmy, Omayma Eldahshan, Mohamed El-Shazly, Elena Codruța Dobrică, Hamed Kord-Varkaneh, Camelia Cristina Diaconu, Mihnea Alexandru Găman Apr 2022

Laboratory Findings In Covid-19 - Alterations Of Hematological, Immunological, Biochemical, Hormonal And Other Lab Panels: A Narrative Review, Yousef Rasmi, Lucas Paulo Jacinto Saavedra, Matei-Alexandru Cozma, Heba El-Nashar, Shaza Aly, Nouran Fahmy, Omayma Eldahshan, Mohamed El-Shazly, Elena Codruța Dobrică, Hamed Kord-Varkaneh, Camelia Cristina Diaconu, Mihnea Alexandru Găman

Journal of Mind and Medical Sciences

Up to the present date, according to the official reports of the World Health Organization (WHO), 205,338,159 patients have been confirmed with the coronavirus disease (COVID-19) and 4,333,094 have died as a consequence of this infectious disorder. The majority of COVID-19 patients will develop hematological, biochemical, immunological, hormonal and other complex alterations of their laboratory data which may be diagnosed using different biomarkers. In this paper, we review the alterations of the hematology, immunology, biochemistry, hormonal and other laboratory panels discovered in the subjects diagnosed with SARS-CoV-2 infection, based on the available data in the literature.


Overcrowded Housing Increases Risk For Covid-19 Mortality: An Ecological Study, Karan Varshney, Talia Glodjo, Jenna R Adalbert Apr 2022

Overcrowded Housing Increases Risk For Covid-19 Mortality: An Ecological Study, Karan Varshney, Talia Glodjo, Jenna R Adalbert

College of Population Health Faculty Papers

Objectives: Overcrowded housing is a sociodemographic variable associated with increased infection and mortality rates from communicable diseases. It is not well understood if this association exists for COVID-19. Our objective was hence to determine the association between household overcrowding and risk of mortality from COVID-19, and this was done by performing bivariable and multivariable analyses using COVID-19 data from cities in Los Angeles County.

Results: Bivariate regression revealed that overcrowded households were positively associated with COVID-19 deaths (standardized β = 0.863, p < 0.001). COVID-19 case totals, people aged 60+, and the number of overcrowded households met conditions for inclusion in the backwards stepwise linear regression model. Analysis revealed all independent variables were positively associated with mortality rates, primarily for individuals 60 + (standardized β1 = 0.375, p = 0.001), followed by overcrowded households (standardized β2 = 0.346, p = 0.014), and total COVID-19 cases (standardized β3 = 0.311, p < 0.001). Our findings highlight that residing in overcrowded households may be an important risk factor for COVID-19 mortality. Public health entities should consider this population when allocating resources for prevention and control of COVID-19 mortality and future disease outbreaks.


Overcrowded Housing Increases Risk For Covid-19 Mortality: An Ecological Study., Karan Varshney, Talia Glodjo, Jenna Adalbert Apr 2022

Overcrowded Housing Increases Risk For Covid-19 Mortality: An Ecological Study., Karan Varshney, Talia Glodjo, Jenna Adalbert

College of Population Health Faculty Papers

OBJECTIVES: Overcrowded housing is a sociodemographic variable associated with increased infection and mortality rates from communicable diseases. It is not well understood if this association exists for COVID-19. Our objective was hence to determine the association between household overcrowding and risk of mortality from COVID-19, and this was done by performing bivariable and multivariable analyses using COVID-19 data from cities in Los Angeles County.

RESULTS: Bivariate regression revealed that overcrowded households were positively associated with COVID-19 deaths (standardized β = 0.863, p < 0.001). COVID-19 case totals, people aged 60+, and the number of overcrowded households met conditions for inclusion in the backwards stepwise linear regression model. Analysis revealed all independent variables were positively associated with mortality rates, primarily for individuals 60 + (standardized β


Safety And Efficacy Of Colchicine In Covid-19 Patients: A Systematic Review And Meta-Analysis Of Randomized Control Trials, Farah Yasmin, Hala Najeeb, Abdul Moeed, Wardah Hassan, Mahima Khatri, Muhammad Sohaib Asghar, Ahmed Kunwer Naveed, Waqas Ullah, Salim Surani Apr 2022

Safety And Efficacy Of Colchicine In Covid-19 Patients: A Systematic Review And Meta-Analysis Of Randomized Control Trials, Farah Yasmin, Hala Najeeb, Abdul Moeed, Wardah Hassan, Mahima Khatri, Muhammad Sohaib Asghar, Ahmed Kunwer Naveed, Waqas Ullah, Salim Surani

Department of Medicine Faculty Papers

Background: Colchicine has been used an effective anti-inflammatory drug to treat gout diseases. Owing to its pharmacodynamic of inhibiting interleukins, it has been repurposed to target the cytokine storm post-SARS-CoV-2 invasion. The goal of this meta-analysis was to evaluate the safety profile of colchicine in COVID-19 patients using the gold-standard randomised-control trials.

Methods: Electronic databases (Pubmed, Google Scholar, and Cochrane) were systematically searched until June 2021 and RCTs were extracted. Outcomes of interest included all-cause mortality, COVID-19 severity, mechanical ventilation, C-reactive protein and D-dimer levels. Using a random-effects model, dichotomous outcomes were pooled using odds ratios (OR) through the generic …


Reducing Central Line-Associated Bloodstream Infections At A Rural Midwestern Hospital Through An Evidence-Based Nurse-Led Practice Change Intervention, Crystal B. Lavalley Apr 2022

Reducing Central Line-Associated Bloodstream Infections At A Rural Midwestern Hospital Through An Evidence-Based Nurse-Led Practice Change Intervention, Crystal B. Lavalley

Doctor of Nursing Practice Scholarly Projects

Central line-associated bloodstream infections (CLABSIs) are responsible for increased patient morbidity, mortality, and healthcare costs, despite being a preventable harm (Barnes et al., 2015; Furuya et al., 2016). Evidence-based (EB) research suggests that the use of central line bundles is the most effective way to reduce CLABSIs in hospitals (Barnes et al., 2015; Furuya et al., 2016). Researchers have also found a statistically significant correlation between nurse compliance with bundle components and CLABSI rates (Aloush & Alsaraireh, 2018; Furuya et al., 2016). The purpose of this study was to determine if a nurse-led collaborative that focused on CLABSI reduction using …