Immunology and Infectious Disease Commons^™

Large-Scale Phenotyping Of Patients With Long Covid Post-Hospitalization Reveals Mechanistic Subtypes Of Disease, Felicity Liew, Claudia Efstathiou, Sara Fontanella, Matthew Richardson, Ruth Saunders, Dawid Swieboda, Jasmin K Sidhu, Stephanie Ascough, Shona C Moore, Noura Mohamed, Jose Nunag, Clara King, Olivia C Leavy, Omer Elneima, Hamish J C Mcauley, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Victoria C Harris, Linzy Houchen-Wolloff, Neil J Greening, Nazir I Lone, Matthew Thorpe, A A Roger Thompson, Sarah L Rowland-Jones, Annemarie B Docherty, James D Chalmers, Ling-Pei Ho, Alexander Horsley, Betty Raman, Krisnah Poinasamy, Michael Marks, Onn Min Kon, Luke S Howard, Daniel G Wootton, Jennifer K Quint, Thushan I De Silva, Antonia Ho, Christopher Chiu, Ewen M Harrison, William Greenhalf, J Kenneth Baillie, Malcolm G Semple, Lance Turtle, Rachael A Evans, Louise V Wain, Christopher Brightling, Ryan S Thwaites, Peter J M Openshaw, Phosp-Covid Collaborative Group, Isaric Investigators

Student and Faculty Publications

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers …

Effect Of Neutralizing Monoclonal Antibody Treatment On Early Trajectories Of Virologic And Immunologic Biomarkers In Patients Hospitalized With Covid-19., Tomas O Jensen, Greg A Grandits, Mamta K Jain, Thomas A Murray, Birgit Grund, Kathryn Shaw-Saliba, Michael A Matthay, Mahsa Abassi, Magdalena Ardelt, Jason V Baker, Peter Chen, Robin L Dewar, Anna L Goodman, Timothy J Hatlen, Helene C Highbarger, Mark Holodniy, Perrine Lallemand, Sylvain Laverdure, Bradley G Leshnower, David Looney, Charalampos D Moschopoulos, Henry Mugerwa, Daniel D Murray, Eleftherios Mylonakis, Stephanie Nagy-Agren, M Tauseef Rehman, Adam Rupert, Randy A Stevens, Stuart Turville, Amy Weintrob, Katherine Wick, Jens Lundgren, Emily R Ko, Activ-3/Tico Study Group

Student and Faculty Publications

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood.

METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models.

RESULTS: Analysis included 2149 participants enrolled between …

The Mrna-Lnp Vaccines - The Good, The Bad And The Ugly?, Botond Z. Igyártó, Zhen Qin

Department of Microbiology and Immunology Faculty Papers

The mRNA-LNP vaccine has received much attention during the COVID-19 pandemic since it served as the basis of the most widely used SARS-CoV-2 vaccines in Western countries. Based on early clinical trial data, these vaccines were deemed safe and effective for all demographics. However, the latest data raise serious concerns about the safety and effectiveness of these vaccines. Here, we review some of the safety and efficacy concerns identified to date. We also discuss the potential mechanism of observed adverse events related to the use of these vaccines and whether they can be mitigated by alterations of this vaccine mechanism …

Efficacy And Safety Of Autologous Tumor-Infiltrating Lymphocytes In Recurrent Or Refractory Ovarian Cancer, Colorectal Cancer, And Pancreatic Ductal Adenocarcinoma, Rodabe Amaria, Anne Knisely, David Vining, Scott Kopetz, Michael J Overman, Milind Javle, Mara B Antonoff, Ching-Wei D Tzeng, Robert A Wolff, Shubham Pant, Kathryn Lito, Kelly Rangel, Bryan Fellman, Ying Yuan, Karen H Lu, Donastas Sakellariou-Thompson, Cara L Haymaker, Marie-Andrée Forget, Patrick Hwu, Chantale Bernatchez, Amir A Jazaeri

Student and Faculty Publications

BACKGROUND: Tumor-infiltrating lymphocyte (TIL) therapy has shown efficacy in metastatic melanoma, non-small cell lung cancer, and other solid tumors. Our preclinical work demonstrated more robust CD8 predominant TIL production when agonistic anti-4-1BB and CD3 antibodies were used in early ex vivo TIL culture.

METHODS: Patients with treatment-refractory metastatic colorectal (CRC), pancreatic (PDAC) and ovarian (OVCA) cancers were eligible. Lymphodepleting chemotherapy was followed by infusion of ex vivo expanded TIL, manufactured at MD Anderson Cancer Center with IL-2 and agonistic stimulation of CD3 and 4-1BB (urelumab). Patients received up to six doses of high-dose IL-2 after TIL infusion. Primary endpoint was …

Assessing The Value And Knowledge Gains From An Online Tick Identification And Tick-Borne Disease Management Course For The Southeastern United States, Catherine A. Lippi, Holly D. Gaff, Alexis L. White, Sadie J. Ryan

Biological Sciences Faculty Publications

Background

Tick-borne diseases are a growing public health threat in the United States. Despite the prevalence and rising burden of tick-borne diseases, there are major gaps in baseline knowledge and surveillance efforts for tick vectors, even among vector control districts and public health agencies. To address this issue, an online tick training course (OTTC) was developed through the Southeastern Center of Excellence in Vector-Borne Diseases (SECOEVBD) to provide a comprehensive knowledge base on ticks, tick-borne diseases, and their management.

Methods

The OTTC consisted of training modules covering topics including tick biology, tick identification, tick-borne diseases, and public health, personal tick …

Phase Ii Trial Of Medi0457 And Durvalumab For Patients With Recurrent/Metastatic Human Papillomavirus-Associated Cancers, Van K Morris, Amir Jazaeri, Shannon N Westin, Curtis Pettaway, Solly George, Ryan W Huey, Michaela Grinsfelder, Aaron Shafer, Benny Johnson, David Vining, Ming Guo, Bryan Fellman, Michael Frumovitz

Student and Faculty Publications

BACKGROUND: Human papillomavirus (HPV) types 16/18 drive oncogenesis for most patients with cervical, anal, and penile cancers. MEDI0457, a therapeutic DNA vaccine containing plasmids for E6 and E7 HPV-16/18 viral oncogenes and IL-12 adjuvant, is safe and provokes an immune response against E6/E7. We tested MEDI0457 with the anti-PD-L1 antibody durvalumab for patients with HPV-associated cancers.

METHODS: Patients with recurrent/metastatic, treatment-refractory HPV-16/18 cervical cancer, or rare HPV-associated (anal and penile) cancers were eligible. Prior immune checkpoint inhibition was not permitted. Patients received MEDI0457 7 mg intramuscularly (weeks 1, 3, 7, 12, and every 8 weeks thereafter) and durvalumab 1500 mg …

Clonal Hematopoiesis Is Associated With Protection From Alzheimer's Disease, Hind Bouzid, Julia A Belk, Max Jan, Yanyan Qi, Chloé Sarnowski, Sara Wirth, Lisa Ma, Matthew R Chrostek, Herra Ahmad, Daniel Nachun, Winnie Yao, Alexa Beiser, Alexander G Bick, Joshua C Bis, Myriam Fornage, William T Longstreth, Oscar L Lopez, Pradeep Natarajan, Bruce M Psaty, Claudia L Satizabal, Joshua Weinstock, Eric B Larson, Paul K Crane, C Dirk Keene, Sudha Seshadri, Ansuman T Satpathy, Thomas J Montine, Siddhartha Jaiswal

Student and Faculty Publications

Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant expansion of mutated hematopoietic stem cells. As CHIP-associated mutations are known to alter the development and function of myeloid cells, we hypothesized that CHIP may also be associated with the risk of Alzheimer's disease (AD), a disease in which brain-resident myeloid cells are thought to have a major role. To perform association tests between CHIP and AD dementia, we analyzed blood DNA sequencing data from 1,362 individuals with AD and 4,368 individuals without AD. Individuals with CHIP had a lower risk of AD dementia (meta-analysis odds ratio (OR) = 0.64, P …

Antibody Duration After Infection From Sars-Cov-2 In The Texas Coronavirus Antibody Response Survey, Michael D Swartz, Stacia M Desantis, Ashraf Yaseen, Frances A Brito, Melissa A Valerio-Shewmaker, Sarah E Messiah, Luis G Leon-Novelo, Harold W Kohl, Cesar L Pinzon-Gomez, Tianyao Hao, Shiming Zhang, Yashar Talebi, Joy Yoo, Jessica R Ross, Michael O Gonzalez, Leqing Wu, Steven H Kelder, Mark Silberman, Samantha Tuzo, Stephen J Pont, Jennifer A Shuford, David Lakey, Eric Boerwinkle

Student and Faculty Publications

Understanding the duration of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that causes COVID-19 is important to controlling the current pandemic. Participants from the Texas Coronavirus Antibody Response Survey (Texas CARES) with at least 1 nucleocapsid protein antibody test were selected for a longitudinal analysis of antibody duration. A linear mixed model was fit to data from participants (n = 4553) with 1 to 3 antibody tests over 11 months (1 October 2020 to 16 September 2021), and models fit showed that expected antibody response after COVID-19 infection robustly increases for 100 days postinfection, and predicts …

Methodology To Estimate Natural- And Vaccine-Induced Antibodies To Sars-Cov-2 In A Large Geographic Region, Stacia M Desantis, Luis G León-Novelo, Michael D Swartz, Ashraf S Yaseen, Melissa A Valerio-Shewmaker, Yashar Talebi, Frances A Brito, Jessica A Ross, Harold W Kohl, Sarah E Messiah, Steve H Kelder, Leqing Wu, Shiming Zhang, Kimberly A Aguillard, Michael O Gonzalez, Onyinye S Omega-Njemnob, David Lakey, Jennifer A Shuford, Stephen Pont, Eric Boerwinkle

Student and Faculty Publications

Accurate estimates of natural and/or vaccine-induced antibodies to SARS-CoV-2 are difficult to obtain. Although model-based estimates of seroprevalence have been proposed, they require inputting unknown parameters including viral reproduction number, longevity of immune response, and other dynamic factors. In contrast to a model-based approach, the current study presents a data-driven detailed statistical procedure for estimating total seroprevalence (defined as antibodies from natural infection or from full vaccination) in a region using prospectively collected serological data and state-level vaccination data. Specifically, we conducted a longitudinal statewide serological survey with 88,605 participants 5 years or older with 3 prospective blood draws beginning …

Disparities In Sars-Cov-2 Positivity Rates: Associations With Race And Ethnicity, Harvey W Kaufman, Justin K Niles, David B. Nash

College of Population Health Faculty Papers

Numerous reports indicate that African Americans and Latinos are being affected disproportionately by coronavirus disease 2019 (COVID-19). Positivity rates have not been analyzed on scale because only 4 states report race/ethnicity as part of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. Previous studies also have had little ability to control for many known risk factors to better identify the effects of COVID-19 on racial and ethnic communities. Using test results from a large national reference laboratory database that included patients from all 50 states and the District of Columbia, this study compared positivity rates for SARS-CoV-2 nucleic acid amplification …

Serological Proteomic Screening And Evaluation Of A Recombinant Egg Antigen For The Diagnosis Of Low-Intensity Schistosoma Mansoni Infections In Endemic Area In Brazil, Vanessa Silva-Moraes, Lisa Marie Shollenberger, William Castro-Borges, Ana Lucia Teles Rabello, Donald A. Harn, Lia Carolina Soares Medeiros, Wander De Jesus Jeremias, Liliane Maria Vidal Siqueira, Caroline Stephane Salviano Pereira, Maria Luysa Camargos Pedrosa, Nathalie Bonatti Franco Almeida, Aureo Almeida, Jose Roberto Lambertucci, Nidia Francisca De Figueiredo Carneiro, Paulo Marcos Zech Coelho, Refaella Fortini Queiroz Grenfell

Biological Sciences Faculty Publications

Background

Despite decades of use of control programs, schistosomiasis remains a global public health problem. To further reduce prevalence and intensity of infection, or to achieve the goal of elimination in low-endemic areas, there needs to be better diagnostic tools to detect low-intensity infections in low-endemic areas in Brazil. The rationale for development of new diagnostic tools is that the current standard test Kato-Katz (KK) is not sensitive enough to detect low-intensity infections in low-endemic areas. In order to develop new diagnostic tools, we employed a proteomics approach to identify biomarkers associated with schistosome-specific immune responses in hopes of developing …

Diagnosis Of Schistosoma Mansoni Infections: What Are The Choices In Brazilian Low-Endemic Areas?, Vanessa Silva-Moraes, Lisa M. Shollenberger, Liliane Maria Vidal Siqueira, William Castro-Borges, Donald A. Harn, Rafaella Fortini Queiroz E. Grenfell, Ana Lucia Teles Rabello, Paulo Marcos Zech Coelho

Biological Sciences Faculty Publications

The population of Brazil is currently characterised by many individuals harbouring low-intensity Schistosoma mansoni infections. The Kato-Katz technique is the diagnostic method recommended by the World Health Organization (WHO) to assess these infections, but this method is not sensitive enough in the context of low egg excretion. In this regard, potential alternatives are being employed to overcome the limits of the Kato-Katz technique. In the present review, we evaluated the performance of parasitological and immunological approaches adopted in Brazilian areas. Currently, the diagnostic choices involve a combination of strategies, including the utilisation of antibody methods to screen individuals and then …

Identification Of Ecdysone Hormone Receptor Agonists As A Therapeutic Approach For Treating Filarial Infections, Amruta S. Mhashilkar, Sai L. Vankayala, Canhui Liu, Fiona Kearns, Priyanka Mehrotra, George Tzertzinis, Subba R. Palli, H. Lee Woodcock, Thomas R. Unnasch

Entomology Faculty Publications

Background A homologue of the ecdysone receptor has previously been identified in human filarial parasites. As the ecdysone receptor is not found in vertebrates, it and the regulatory pathways it controls represent attractive potential chemotherapeutic targets.

Methodology/ Principal Findings Administration of 20-hydroxyecdysone to gerbils infected with B. malayi infective larvae disrupted their development to adult stage parasites. A stable mammalian cell line was created incorporating the B. malayi ecdysone receptor ligand-binding domain, its heterodimer partner and a secreted luciferase reporter in HEK293 cells. This was employed to screen a series of ecdysone agonist, identifying seven agonists active at …