Medical Sciences Commons^™

Hand Hygiene Roles, Challenges, And Intervention Feedback From School Staff: A Qualitative Analysis, Belize, 2022-2023, Anh N Ly, Christina Craig, Dian Maheia, Yolanda Gongora, Vickie Romero, Rosalva Blanco, Allison Lino, Kelsey Mcdavid, Allison Stewart, Victoria Trinies, Alexandra Medley, Francis Morey, Russell Manzanero, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Hand hygiene (HH) in school settings can reduce the spread of infectious diseases and student absenteeism due to illness. During the COVID-19 pandemic, the World Health Organization recommended HH as a public health measure to prevent disease transmission. Understanding school staff's experiences with school-based programs is important for future program development and improvement. As part of a mixed-methods study, we conducted in-depth interviews in March 2022 with school administrators and teachers at 12 primary schools in Belize, selected based on high gaps in HH resources, to understand HH responsibilities, supplies, and challenges. An intervention was implemented to increase HH knowledge …

Turning Analysis Into Action: Opportunities And Challenges In Implementing Wastewater Science For Public Health Decision-Making, Anna Gitter, Valeria Ruvalcaba, Katelyn Clark, Theresa Tran Carapucci, Fuqing Wu, Blake M Hanson, Jennifer Deegan, John Balliew, Eric Boerwinkle, Anthony W Maresso, Kristina D Mena

Faculty, Staff and Students Publications

In the 5 years since the emergence of the COVID-19 pandemic, the field of wastewater-based epidemiology (WBE) has dramatically expanded with programs implemented across the globe to monitor for SARS-CoV-2 and other viruses of public health concern. However, the best way to use wastewater surveillance data and inform local communities of the utility of wastewater science remains limited and sporadically discussed. Specifically, there is vague guidance regarding interpreting varying levels of viral loads in wastewater for public health significance. While collaborative efforts are key to implementing these community-specific wastewater surveillance programs, effectively using the data for public health decision-making still …

Histone Methyltransferase Ash1l Primes Metastases And Metabolic Reprogramming Of Macrophages In The Bone Niche, Chenling Meng, Kevin Lin, Wei Shi, Hongqi Teng, Xinhai Wan, Anna Debruine, Yin Wang, Xin Liang, Javier Leo, Feiyu Chen, Qianlin Gu, Jie Zhang, Vivien Van, Kiersten L Maldonado, Boyi Gan, Li Ma, Yue Lu, Di Zhao

Faculty, Staff and Student Publications

Bone metastasis is a major cause of cancer death; however, the epigenetic determinants driving this process remain elusive. Here, we report that histone methyltransferase ASH1L is genetically amplified and is required for bone metastasis in men with prostate cancer. ASH1L rewires histone methylations and cooperates with HIF-1α to induce pro-metastatic transcriptome in invading cancer cells, resulting in monocyte differentiation into lipid-associated macrophage (LA-TAM) and enhancing their pro-tumoral phenotype in the metastatic bone niche. We identified IGF-2 as a direct target of ASH1L/HIF-1α and mediates LA-TAMs' differentiation and phenotypic changes by reprogramming oxidative phosphorylation. Pharmacologic inhibition of the ASH1L-HIF-1α-macrophages axis elicits …

Science Tikkun: A Bioscience Pandemic Framework In A Hebrew Tradition Of Global Repair, Peter Hotez

Center for Medical Ethics and Health Policy Staff Publications

Over the past decade we have seen a steady increase in dangerous pandemic threats. They include two major Ebola epidemics and cholera in Africa; dengue, Zika, yellow fever in the Americas; a COVID-19 pandemic; and H5N1 in Texas. This is happening because of a confluence of modern forces including urbanization, deforestation, and climate change. Yet as pandemics emerge on a crowded and warming planet, anti-science disinformation and antisemitism impede our response. Science tikkun is an overarching framework for repair and redress. It honors the legacy of Maimonides, Teilhard de Chardin, and others who have sought reconciliation between science and religion.

Covid-19 Infection History As A Risk Factor For Early Pregnancy Loss: Results From The Electronic Health Record-Based Southeast Texas Covid And Pregnancy Cohort Study, Micaela N Sandoval, Michelle R Klawans, Mackinsey A Bach, Jennifer Mikhail, Edward A Graviss, Tru Cao, Jacqueline G Parchem, Junaid Husain, Eric Boerwinkle

Faculty, Staff and Student Publications

Background: The effects of SARS-CoV-2 infection before or during pregnancy on pregnancy outcomes are still largely unknown. We hypothesized that COVID-19 in early pregnancy is a risk factor for adverse pregnancy outcomes, particularly miscarriage.

Methods: We examined the relationship between COVID-19 and adverse pregnancy outcomes, including spontaneous abortion, ectopic pregnancy, and preterm delivery in a large, retrospective, electronic health record (EHR)-based cohort, from 2019 to 2023. Generalized estimating equation modeling was performed to identify risk factors for adverse pregnancy outcomes. Study exposures included COVID-19 before pregnancy, COVID-19 during pregnancy, age, race/ethnicity, comorbidity burden, and neighborhood-level social vulnerability.

Results: In the …

Evaluating The Test-Negative Design For Covid-19 Vaccine Effectiveness Using Randomized Trial Data: A Secondary Cross-Protocol Analysis Of 5 Randomized Clinical Trials, Leah I B Andrews, M Elizabeth Halloran, Kathleen M Neuzil, Lars Van Der Laan, Yunda Huang, Jessica Andriesen, Mayur Patel, Leigh H Fisher, Holly Janes, Nadine Rouphael, Stephen R Walsh, Deborah A Theodore, Hong-Van Tieu, Magdalena Sobieszczyk, Hana M El Sahly, Lindsey R Baden, Ann R Falsey, Thomas B Campbell, Colleen F Kelley, Catherine Mary Healy, Lilly Immergluck, Benjamin Luft, Ian Hirsch, Guy De Bruyn, Carla Truyers, Frances Priddy, Kelsey M Sumner, Brendan Flannery, Dean Follmann, Peter B Gilbert, Covid-19 Prevention Network (Covpn)

Faculty, Staff and Students Publications

Importance: The test-negative design (TND) has been widely used to assess postmarketing COVID-19 vaccine effectiveness but requires further evaluation for this application.

Objective: To determine whether the TND reliably evaluates vaccine effectiveness against symptomatic COVID-19 using placebo-controlled vaccine efficacy randomized clinical trials (RCTs).

Design, setting, and participants: This secondary cross-protocol analysis constructed TND study datasets from study sites in 16 countries across 5 continents using the blinded phase cohorts of 5 harmonized phase 3 COVID-19 Prevention Network RCTs: COVE (Coronavirus Vaccine Efficacy and Safety), AZD1222, ENSEMBLE, PREVENT-19 (Prefusion Protein Subunit Vaccine Efficacy Novavax Trial COVID-19), and VAT00008. Participants included adults …

From Epithelium To Therapy: Transitional Cells In Lung Fibrosis, Sarah Y Shin, Jichao Chen, Irit Milman Krentsis, Yair Reisner, Rodeo Abrencillo, Rahat Hussain, Danielle Wu, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Patients with idiopathic pulmonary fibrosis and lung fibrosis secondary to infections such as influenza A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have limited treatment options outside of supportive therapy and lung transplantation. Multiple lung stem cell populations have been implicated in the pathogenesis of lung fibrosis, and more progenitor cell populations continue to be discovered and characterized. In this review, we summarize the functions and differentiation pathways of various cells that constitute the lung epithelium. We then focus on two subpopulations of KRT5

Distinguishing Multisystem Inflammatory Syndrome In Children From Typhus Using Artificial Intelligence: Mis-C Versus Endemic Typhus (Ai-Met), Angela Chun, Abraham Bautista-Castillo, Isabella Osuna, Kristiana Nasto, Flor M Munoz, Gordon E Schutze, Sridevi Devaraj, Eyal Muscal, Marietta M De Guzman, Kristen Sexson Tejtel, Tiphanie P Vogel, Ioannis A Kakadiaris

Faculty, Staff and Students Publications

Background: The pandemic emergent disease multisystem inflammatory syndrome in children (MIS-C) following coronavirus disease-19 infection can mimic endemic typhus. We aimed to use artificial intelligence (AI) to develop a clinical decision support system that accurately distinguishes MIS-C versus endemic typhus (MET).

Methods: Demographic, clinical, and laboratory features rapidly available following presentation were extracted for 133 patients with MIS-C and 87 patients hospitalized due to typhus. An attention module assigned importance to inputs used to create the 2-phase AI-MET. Phase 1 uses 17 features to arrive at a classification manually (MET-17). If the confidence level is not surpassed, 13 additional features …

Early Nintedanib Deployment In Covid-19 Interstitial Lung Disease (Endcov-I): Study Protocol Of A Randomised, Double-Blind, Placebo-Controlled Trial, Valeria Santibanez, Aditi Mathur, Jigna Zatakia, Nicole Ng, Michele Cohen, Emilia Bagiella, Stacey-Ann Brown, Ivan O Rosas, Nina M Patel, Amy Olson, Peide Li, Maria Padilla

Faculty, Staff and Students Publications

Introduction: In December 2019, the novel SARS-CoV-2 triggered a global pneumonia outbreak, leading to millions of deaths worldwide. A subset of survivors faces increased morbidity and mortality, particularly due to subacute lung injury evolving to chronic fibrosing interstitial lung disease. While nintedanib, a tyrosine-kinase inhibitor, shows promise in treating progressive fibrotic lung disease, limited randomised trial data exists for post-COVID-19-induced lung injury. We hypothesise that treatment with nintedanib may attenuate advancement to the fibrotic stages, offering a potential avenue for improving outcomes in this specific patient subset.

Methods and analysis: We describe the design of a multicentre, randomised, double-blind, placebo-controlled …

The Burden Of Steatotic Liver Disease Before And During The Covid-19 Pandemic: Correspondence To Editorial On “Current Burden Of Steatotic Liver Disease And Fibrosis Among Adults In The United States, 2017–2023”, Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Rohit Loomba, Aijaz Ahmed

Faculty, Staff and Students Publications

No abstract provided.

Single-Nucleus Transcriptional Profiling Of The Placenta Reveals The Syncytiotrophoblast Stress Response To Covid-19, Rachel A Keuls, Scott A Ochsner, Mary B O'Neill, Diana R O'Day, Akihiko Miyauchi, Kadeshia M Campbell, Natalie Lanners, Jeffery A Goldstein, Connor Yee, Neil J Mckenna, Ronald J Parchem, Jacqueline G Parchem

Faculty, Staff and Students Publications

Background: COVID-19 in pregnancy is associated with placental immune activation, inflammation, and vascular malperfusion, but its impact on syncytiotrophoblast biology and function is unclear.

Objective: This study aimed to determine the effects of maternal COVID-19 on placental syncytiotrophoblasts using single-nucleus transcriptional profiling and to compare placental stress responses in COVID-19 and preeclampsia.

Study design: For transcriptional characterization of syncytiotrophoblasts, we used the single-nucleus RNA sequencing platform, single-cell combinatorial indexing RNA sequencing (sci-RNA-seq3), to profile placental villi and fetal membranes from unvaccinated patients with symptomatic COVID-19 at birth (n = 4), gestational age-matched controls (n = 4), and a case of …

Current Burden Of Steatotic Liver Disease And Fibrosis Among Adults In The United States, 2017-2023, Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Rohit Loomba, Aijaz Ahmed

Faculty, Staff and Students Publications

Background/aims: Multi-society experts proposed the adoption of new terminology, metabolic dysfunctionassociated steatotic liver disease (MASLD) and steatotic liver disease (SLD). We studied the current prevalence of SLD and its subcategories in the US.

Methods: Using the recent National Health and Nutrition Examination Survey from 2017 to 2023, we analyzed data from 12,199 participants (≥18 years) who completed transient elastography. SLD and its subcategories, including MASLD, metabolic and alcohol-related liver disease (MetALD), and alcohol-related liver disease (ALD), were categorized according to consensus nomenclature.

Results: The age-adjusted prevalence of SLD (cut-off: 285 dB/m) was 35.0% (95% confidence interval [CI] 33.4-36.7). Within this …

Cytokine Storms In Covid-19, Hemophagocytic Lymphohistiocytosis, And Car-T Therapy, James P Long, Rishab Prakash, Paul Edelkamp, Mark Knafl, Anath C Lionel, Ranjit Nair, Sairah Ahmed, Paolo Strati, Luis E Malpica Castillo, Ajlan Al-Zaki, Kelly Chien, Dai Chihara, Jason Westin, Fareed Khawaja, Loretta J Nastoupil, Victor Mulanovich, Andrew Futreal, Scott E Woodman, Naval G Daver, Christopher R Flowers, Sattva Neelapu, Joanna-Grace Manzano, Swaminathan P Iyer

Faculty, Staff and Student Publications

Importance: Cytokine storm (CS) is a hyperinflammatory syndrome causing multiorgan dysfunction and high mortality, especially in patients with malignant hematologic neoplasms. Triggers include malignant neoplasm-associated hemophagocytic lymphohistiocytosis (MN-HLH), cytokine release syndrome from chimeric antigen receptor T-cell therapy (CAR-T CRS), and COVID-19, but the underlying mechanisms of inflammation and their impact on outcomes are poorly understood.

Objective: To delineate the inflammatory patterns characterizing different CS etiologies and their association with clinical outcomes.

Design, setting, and participants: This retrospective cohort study was conducted at the MD Anderson Cancer Center in Houston, Texas, between March 1, 2020, and November 20, 2022, using the …

The Influence Of Improved Access To Alcohol-Based Hand Rub And Hand Hygiene Training In Healthcare Facilities On Hand Hygiene Adherence In Belize During Covid-19: June 2021-August 2022., Kelsey Mcdavid, Anh N Ly, Nicholas Bivens, Francis Morey, Gerhaldine Morazan, Russell Manzanero, Melissa Musa-Diaz, Alexandra Medley, Kristy O Murray, Matthew J Lozier

Faculty, Staff and Students Publications

Access to hand hygiene (HH) resources in clinical settings is important to prevent healthcare-associated infections, including COVID-19. However, many countries, including Belize, have limited national data on the availability of HH resources and healthcare worker (HCW) hand hygiene adherence (HHA) in healthcare facilities (HCFs). We conducted a study in the 11 largest public HCFs across Belize to evaluate access to HH resources and HHA before and after an intervention (provision of alcohol-based hand rub (ABHR) wall mounts and HH training). Descriptive statistics and multilevel logistic regressions were used to assess changes in HH resources and HHA from baseline to follow-up …

Amniotic Fluid-Derived Mesenchymal Stem Cells As A Therapeutic Tool Against Cytokine Storm: A Comparison With Umbilical Cord Counterparts, Salvatore Vaiasicca, David W James, Gianmarco Melone, Omar Saeed, Lewis W Francis, Bruna Corradetti

Faculty, Staff and Students Publications

Background: Several immunosuppressive therapies have been proposed as key treatment options for critically ill patients since the first appearance of severe acute respiratory syndrome coronavirus 2. Mesenchymal stem cells (MSCs) from different sources have been considered for their potential to attenuate the cytokine storm associated to COVID-19 and the consequent multi-organ failure, providing evidence for safe and efficacious treatments. Among them, administration of umbilical cord-derived MSCs (UC-MSCs) has demonstrated a significant increase in survival rates, largely due to their potent immunosuppressive properties.

Methods: We applied next-generation sequencing (NGS) analysis to compare the transcriptomic profiles of MSCs isolated from two gestational …

Dock2 Deficiency And Gata2 Haploinsufficiency Can Underlie Critical Coronavirus Disease 2019 (Covid-19) Pneumonia, Sajjad Biglari, Leila Youssefian, Mohammad Amin Tabatabaiefar, Amir Hossein Saeidian, Bahareh Abtahi-Naeini, Erfan Khorram, Roya Sherkat, Atefeh Sohanforooshan Moghaddam, Fatemeh Mohaghegh, Maziyar Rahimi, Hamid Rahimi, Sharareh Babaei, Mohammad Shahrooei, Nikoo Mozafari, Shirin Zaresharifi, Fatemeh Vahidnezhad, Vida Homayouni, Lam C Tsoi, Johann E Gudjonsson, Hakon Hakonarson, Jean-Laurent Casanova, Emmanuelle Jouanguy, Vivien Béziat, Qian Zhang, Aurélie Cobat, Hassan Vahidnezhad

Faculty, Staff and Students Publications

The life-threatening coronavirus disease 2019 (COVID-19) affects about 1 in 1,000 healthy people under 50 without underlying conditions. Among patients with critical COVID-19 pneumonia, rare germline variants at genes controlling type I IFN immunity have been reported in up to 5% of patients. Causal etiologies in 80-85% of cases are still unknown. We analyzed two families with hypoxemic COVID-19 pneumonia for known single-gene inborn errors of immunity. In Family 1, two siblings with critical COVID-19 were homozygous for a DOCK2 variant, c.3624+5G>A. DOCK2 deficiency is a known T-cell disorder underlying severe viral diseases. The variant resulted in skipping exon …

Association Of Messenger Rna Coronavirus Disease 2019 (Covid-19) Vaccination And Reductions In Post Covid Conditions Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection In A Us Prospective Cohort Of Essential Workers, Josephine Mak, Sana Khan, Amadea Britton, Spencer Rose, Lisa Gwynn, Katherine D Ellingson, Jennifer Meece, Leora R Feldstein, Harmony Tyner, Laura J Edwards, Matthew S Thiese, Allison Naleway, Manjusha Gaglani, Natasha Solle, Jefferey L Burgess, Julie Mayo Lamberte, Meghan Shea, Taryn Hunt-Smith, Alberto Caban-Martinez, Cynthia Porter, Ryan Wiegand, Ramona Rai, Kurt T Hegmann, James Hollister, Ashley Fowlkes, Meredith Wesley, Andrew L Philips, Patrick Rivers, Robin Bloodworth, Gabriella Newes-Adeyi, Lauren E W Olsho, Sarang K Yoon, Sharon Saydah, Karen Lutrick

Center for Medical Ethics and Health Policy Staff Publications

Background: Data are limited on whether vaccination reduces post COVID conditions (PCCs) risk after less severe nonhospitalized coronavirus disease 2019 (COVID-19). This study assessed whether COVID-19 vaccination protected against PCCs in persons with mild initial infections during Delta and Omicron variant predominance.

Methods: This study utilized a case-control design, nested within the HEROES-RECOVER cohort. Participants aged ≥18 years with test-confirmed severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) between 28 June 2021 and 14 September 2022 were surveyed for PCCs, defined by symptoms lasting >4 weeks after initial infection. Cases self-reported PCCs and controls self-reported no PCCs. The exposure was …

Impact Of Changes In Gestational Diabetes Mellitus Diagnostic Criteria During The Covid-19 Pandemic, Jessica Neville, Kelly Foley, Seán Lacey, Antoinette Tuthill, Oratile Kgosidialwa, Mairead O’Riordan, Fiona O’Halloran, Seán J. Costelloe

Department of Biological Sciences Publications

Background/Aims

During the COVID-19 pandemic, the Health Service Executive (HSE) and Royal College of Obstetricians and Gynaecologists (RCOG) recommended fasting and random plasma glucose (FPG/RPG) alongside glycated haemoglobin (HbA1c) to replace the oral glucose tolerance test (OGTT) for diagnosing Gestational Diabetes Mellitus (GDM).

Methods

The study compared testing patterns and diagnostic rates for GDM before and after implementing the RCOG guidelines (01/05/2020) in pregnancies beginning 01/11/2018 to 31/03/2021. Trends were inspected using Cochrane-Armitage tests. Differences between General Practice (GP) and Secondary Care (SCare) were assessed by chi-square analysis. A significance level of p <  0.05 was used for all analyses. Information on maternal and pregnancy characteristics was accessed where available.

Results

Data indicated a significant reduction in …

Rising Mortality Rates Linked To Type-2 Diabetes And Obesity In The United States: An Observational Analysis From 1999 To 2022, Mushood Ahmed, Abdullah Nofal, Aimen Shafiq, Hira Javaid, Areeba Ahsan, Zain Ali Nadeem, Raheel Ahmed, Mahboob Alam, Mamas A Mamas, Marat Fudim, Gregg C Fonarow

Faculty, Staff and Students Publications

Background: The prevalence of type 2 diabetes (T2D) and obesity are increasing in the United States. However, population-level data for mortality trends due to T2D and obesity are limited. This study aims to assess these death trends among adults in the United States categorized by sex, race, and geographical location.

Methods: We queried the CDC-WONDER database for multiple cause of death data of adults aged ≥25 years. The crude mortality rates (CMR), age-adjusted mortality rates (AAMRs), annual percent change (APC), and the average APC (AAPC) along with a 95% confidence interval (CI) were analyzed.

Results: From 1999 to 2022, a …

Invasive Haemophilus Influenzae Disease At A Us Children's Hospital In The Sars-Cov-2 Era, J Chase Mcneil, David R Mcdonald, James J Dunn, Sheldon L Kaplan, Kristina G Hulten, Jesus G Vallejo

Faculty, Staff and Students Publications

Background: National data previously demonstrated an increase in invasive disease due to non-type b Haemophilus influenzae from the 2000s to the 2010s. Significant shifts in the epidemiology of respiratory pathogens in children have occurred in the post-SARS-CoV-2 era. We examined pediatric invasive H. influenzae disease in the pre- and post-SARS-CoV-2 years.

Methods: Invasive H. influenzae infections were identified from culture records of the Texas Children's Hospital microbiology laboratory from January 2011 to December 2023. Invasive cases were considered those with isolation of H. influenzae from a sterile site. The annual number of cases/1000 admissions was used as a surrogate for …

Complement Activity And Autophagy Are Dysregulated In The Lungs Of Patients With Nonresolvable Covid-19 Requiring Lung Transplantation, Pooja Shivshankar, Stacey L Mueller-Ortiz, Aleksey Y Domozhirov, Weizhen Bi, Scott D Collum, Marie-Francoise Doursout, Manish Patel, Isabella N Lefebvre, Bindu Akkanti, Simon Yau, Howard J Huang, Rahat Hussain, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) pandemic has challenged the current understanding of the complement cascade mechanisms of host immune responses during infection-induced nonresolvable lung disease. While the complement system is involved in opsonization and phagocytosis of the invading pathogens, uncontrolled complement activation also leads to aberrant autophagic response and tissue damage. Our recent study revealed unique pathologic and fibrotic signature genes associated with epithelial bronchiolization in the lung tissues of patients with nonresolvable COVID-19 (NR-COVID-19) requiring lung transplantation. However, there is a knowledge gap if complement components are modulated to contribute to tissue …

Axl Signaling In Cancer: From Molecular Insights To Targeted Therapies, Monika Yadav, Akansha Sharma, Ketki Patne, Saba Tabasum, Jyoti Suryavanshi, Laxminarayan Rawat, Marc Machaalani, Marc Eid, Rana Singh, Toni Choueiri, Soumitro Pal, Akash Sabarwal

Department of Microbiology and Immunology Faculty Papers

AXL, a member of the TAM receptor family, has emerged as a potential target for advanced-stage human malignancies. It is frequently overexpressed in different cancers and plays a significant role in various tumor-promoting pathways, including cancer cell proliferation, invasion, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, stemness, DNA damage response, acquired therapeutic resistance, immunosuppression, and inflammatory responses. Beyond oncology, AXL also facilitates viral infections, including SARS-CoV-2 and Zika highlighting its importance in both cancer and virology. In preclinical models, small-molecule kinase inhibitors targeting AXL have shown promising anti-tumorigenic potential. This review primarily focuses on the induction, regulation and biological functions of AXL …

Neutralizing Antibody Immune Correlates For A Recombinant Protein Vaccine In The Covail Trial, Youyi Fong, Lauren Dang, Bo Zhang, Jonathan Fintzi, Shiyu Chen, Jing Wang, Nadine G Rouphael, Angela R Branche, David J Diemert, Ann R Falsey, Cecilia Losada, Lindsey R Baden, Sharon E Frey, Jennifer A Whitaker, Susan J Little, Satoshi Kamidani, Emmanuel B Walter, Richard M Novak, Richard Rupp, Lisa A Jackson, Chenchen Yu, Craig A Magaret, Cindy Molitor, Bhavesh Borate, Tara M Babu, Angelica C Kottkamp, Anne F Luetkemeyer, Lilly C Immergluck, Rachel M Presti, Martín Bäcker, Patricia L Winokur, Siham M Mahgoub, Paul A Goepfert, Dahlene N Fusco, Robert L Atmar, Christine M Posavad, Jinjian Mu, Mat Makowski, Mamodikoe K Makhene, Seema U Nayak, Paul C Roberts, Dean Follmann, Peter B Gilbert

Faculty, Staff and Students Publications

For COVAIL recipients of a coronavirus disease 2019 (COVID-19) Sanofi booster vaccine, neutralizing antibody titers were assessed as a correlate of risk (CoR) of COVID-19. Peak and exposure-proximal titers were inverse CoRs with covariate-adjusted hazard ratios (95% confidence intervals) 0.30 (0.11, 0.78) and 0.25 (0.07, 0.85) per 10-fold increase in weighted average titer.

A Randomized, Double-Blind, Placebo-Controlled Trial Of Il-7 In Critically Ill Patients With Covid-19, Manu Shankar-Hari, Bruno Francois, Kenneth E Remy, Cristina Gutierrez, Stephen Pastores, Thomas Daix, Robin Jeannet, Jane Blood, Andrew H Walton, Reinaldo Salomao, Georg Auzinger, David Striker, Robert S Martin, Nitin J Anand, James Bosanquet, Teresa Blood, Scott Brakenridge, Lyle L Moldawer, Vidula Vachharajani, Cassian Yee, Felipe Dal-Pizzol, Michel Morre, Frederique Berbille, Marcel Van Den Brink, Richard Hotchkiss

Faculty, Staff and Student Publications

Background: Lymphopenia and failure of lymphocytes to mount an early IFN-γ response correlate with increased mortality in COVID-19. Given the essential role of CD4 helper and CD8 cytotoxic cells in eliminating viral pathogens, this profound loss in lymphocytes may impair patients' ability to eliminate the virus. IL-7 is a pleiotropic cytokine that is obligatory for lymphocyte survival and optimal function.

Methods: We conducted a prospective, double-blind, randomized, placebo-controlled trial of CYT107, recombinant human IL-7, in 109 critically ill, patients with lymphopenia who have COVID-19. The primary endpoint was to assess CYT107's effect on lymphocyte recovery with secondary clinical endpoints including …

Skin Manifestations And Related Clinical Characteristics Of Multisystem Inflammatory Syndrome In Children: A Descriptive Retrospective Cohort Study At Texas Children’S Hospital, Matthew Penna, Lauren Pupa, Grace Lee, Soo Jung Kim

Faculty, Staff and Students Publications

BACKGROUND: Little is known about the dermatologic manifestations of multisystem inflammatory syndrome in children (MIS-C) in children and adolescents.

OBJECTIVE: We sought to describe the demographic background, key clinical features, and the clinical consequences of developing rash manifestations in MIS-C patients at Texas Children's Hospital.

METHODS: Descriptive retrospective cohort study of 290 hospitalized eligible patients between May 2020 and April 2022.

RESULTS: Among MIS-C patients, 51% exhibited a rash. We found that younger children (8.62 vs 9.49 years of age,

LIMITATIONS: Rash characteristics were initially described by a variety of physicians in the pediatric primary care services.

CONCLUSION: Rash manifestations …

Hybrid Versus Vaccine Immunity Of Mrna-1273 Among People Living With Hiv In East And Southern Africa: A Prospective Cohort Analysis From The Multicentre Covpn 3008 (Ubuntu) Study, Nigel Garrett, Asa Tapley, Aaron Hudson, Sufia Dadabhai, Bo Zhang, Nyaradzo M Mgodi, Jessica Andriesen, Azwidihwi Takalani, Leigh H Fisher, Jia Jin Kee, Craig A Magaret, Manuel Villaran, John Hural, Erica Andersen-Nissen, Guido Ferarri, Maurine D Miner, Bert Le Roux, Eduan Wilkinson, Richard Lessells, Tulio De Oliveira, Jackline Odhiambo, Parth Shah, Laura Polakowski, Margaret Yacovone, Taraz Samandari, Zvavahera Chirenje, Peter James Elyanu, Joseph Makhema, Ethel Kamuti, Harriet Nuwagaba-Biribonwoha, Sharlaa Badal-Faesen, William Brumskine, Soritha Coetzer, Rodney Dawson, Sinead Delany-Moretlwe, Andreas Henri Diacon, Samantha Fry, Katherine Margaret Gill, Zaheer Ahmed Ebrahim Hoosain, Mina C Hosseinipour, Mubiana Inambao, Craig Innes, Steve Innes, Dishiki Kalonji, Margaret Kasaro, Priya Kassim, Noel Kayange, William Kilembe, Fatima Laher, Moelo Malahleha, Vongane Louisa Maluleke, Grace Mboya, Kirsten Mcharry, Essack Mitha, Kathryn Mngadi, Pamela Mda, Tumelo Moloantoa, Cissy Kityo Mutuluuza, Nivashnee Naicker, Vimla Naicker, Anusha Nana, Annet Nanvubya, Maphoshane Nchabeleng, Walter Otieno, Elsje Louise Potgieter, Disebo Potloane, Zelda Punt, Jamil Said, Yashna Singh, Mohammed Siddique Tayob, Yacoob Vahed, Deo Ogema Wabwire, M Juliana Mcelrath, James G Kublin, Linda-Gail Bekker, Peter B Gilbert, Lawrence Corey, Glenda E Gray, Yunda Huang, Philip Kotze, Covpn 3008 Ubuntu Study Team

Faculty, Staff and Students Publications

BACKGROUND: With limited access to mRNA COVID-19 vaccines in lower income countries, and people living with HIV (PLWH) largely excluded from clinical trials, Part A of the multicentre CoVPN 3008 (Ubuntu) study aimed to assess the safety of mRNA-1273, the relative effectiveness of hybrid versus vaccine immunity, and SARS-CoV-2 viral persistence among PLWH in East and Southern Africa during the omicron outbreak.

METHODS: Previously unvaccinated adults with HIV and/or other comorbidities associated with severe COVID-19 received either one (hybrid immunity) or two (vaccine immunity) 100-mcg doses of ancestral strain mRNA-1273 in the first month, depending on baseline evidence of prior …

Association Of Systemic Inflammation And Long-Term Dysfunction In Covid-19 Patients: A Prospective Cohort, Felipe Dal-Pizzol, Bruno Kluwe-Schiavon, Henrique Ritter Dal-Pizzol, Gabriele Da Silveira Prestes, Diogo Dominguini, Carolina Saibro Girardi, Lucas Santos, José Cláudio Fonseca Moreira, Daniel Pens Gelain, Roger Walz, Tatiana Barichello, Cristiane Ritter

Faculty, Staff and Student Publications

COVID-19 has significant long-term impacts, including a chronic syndrome known as long-COVID, characterized by persistent symptoms post-recovery. The inflammatory response during acute infection is hypothesized to influence long-term outcomes. This study aimed to identify inflammatory biomarkers predictive of functional outcomes one year after hospital discharge. A prospective cohort study was conducted with 213 COVID-19 patients admitted to ICUs in Southern Brazil between June and November 2020. After exclusions and follow-ups, 109 patients were evaluated for one-year post-discharge. Plasma levels of Th1 (TNF-α, INF-γ, IL-12), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), and Th17 (IL-17, IL-22) cytokines were measured. Functional outcomes in …

Neutralizing Antibody Immune Correlates In Covail Trial Recipients Of An Mrna Second Covid-19 Vaccine Boost, Bo Zhang, Youyi Fong, Lauren Dang, Jonathan Fintzi, Shiyu Chen, Jing Wang, Nadine G Rouphael, Angela R Branche, David J Diemert, Ann R Falsey, Daniel S Graciaa, Lindsey R Baden, Sharon E Frey, Jennifer A Whitaker, Susan J Little, Satoshi Kamidani, Emmanuel B Walter, Richard M Novak, Richard Rupp, Lisa A Jackson, Chenchen Yu, Craig A Magaret, Cindy Molitor, Bhavesh Borate, Sydney Busch, David Benkeser, Antonia Netzl, Derek J Smith, Tara M Babu, Angelica C Kottkamp, Anne F Luetkemeyer, Lilly C Immergluck, Rachel M Presti, Martín Bäcker, Patricia L Winokur, Siham M Mahgoub, Paul A Goepfert, Dahlene N Fusco, Robert L Atmar, Christine M Posavad, Jinjian Mu, Mat Makowski, Mamodikoe K Makhene, Seema U Nayak, Paul C Roberts, Peter B Gilbert, Dean Follmann

Faculty, Staff and Students Publications

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 ("COVID-19") and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. …

Characterization Of Vaccine-Enhanced Humoral Immune Responses Against Emergent Sars-Cov-2 Variants In A Convalescent Cohort, Jared Sheehan, Amber J. Trauth, Michael E. Hagensee, Alistair J. Ramsay

School of Graduate Studies Faculty Publications

Vaccination of COVID-19–convalescent individuals may generate ‘hybrid’ immunity of enhanced magnitude, durability, and cross-reactive breadth. Our primary goal was to characterize hybrid antibody (Ab) responses in a patient cohort infected with ancestral Wuhan-Hu-1 virus and vaccinated between 6 and 10 months later with the Wuhan-Hu-1–based BNT162b2 mRNA vaccine. We were particularly interested in determining the efficacy of neutralizing Ab responses against subsequently emergent SARS-CoV-2 variants. Sera collected at 3-monthly intervals over a period of 12 months were analyzed by ELISA for SARS-CoV-2 RBD–specific Ab responses, and also for neutralizing Ab activity using pseudovirus-based neutralization assays. We found that convalescent RBD-reactive …

A Regularized Bayesian Dirichlet-Multinomial Regression Model For Integrating Single-Cell-Level Omics And Patient-Level Clinical Study Data, Yanghong Guo, Lei Yu, Lei Guo, Lin Xu, Qiwei Li

Faculty, Staff and Student Publications

The abundance of various cell types can vary significantly among patients with varying phenotypes and even those with the same phenotype. Recent scientific advancements provide mounting evidence that other clinical variables, such as age, gender, and lifestyle habits, can also influence the abundance of certain cell types. However, current methods for integrating single-cell-level omics data with clinical variables are inadequate. In this study, we propose a regularized Bayesian Dirichlet-multinomial regression framework to investigate the relationship between single-cell RNA sequencing data and patient-level clinical data. Additionally, the model employs a novel hierarchical tree structure to identify such relationships at different cell-type …