Life Sciences Commons^™

Physical Exercise-Related Manifestations Of Long Covid: A Systematic Review And Meta-Analysis, Chen Zheng, Jun-Jie Chen, Zi-Han Dai, Ke-Wen Wan, Feng-Hua Sun, Jun-Hao Huang, Xiang-Ke Chen

Student and Faculty Publications

OBJECTIVE: This study aims to systematically assess physical exercise-related symptoms of post-acute sequelae of SARS-CoV-2 infection (PASC or long COVID) in coronavirus disease 2019 (COVID-19) survivors.

METHODS: Eight databases were systematically searched on March 03, 2024. Original studies that compared physical exercise-related parameters measured by exercise testing between COVID-19 survivors who recovered from SARS-CoV-2 infection over 3 months and non-COVID-19 controls were included. A random-effects model was utilized to determine the mean differences (MDs) or standardized MDs in the meta-analysis.

RESULTS: A total of 40 studies with 6241 COVID-19 survivors were included. The 6-min walk test, maximal oxygen consumption (VO …

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 …

Pre-Covid-19 Hospital Quality And Hospital Response To Covid-19: Examining Associations Between Risk-Adjusted Mortality For Patients Hospitalised With Covid-19 And Pre-Covid-19 Hospital Quality, Doris Peter, Shu-Xia Li, Yongfei Wang, Jing Zhang, Jacqueline Grady, Kerry Mcdowell, Erica Norton, Zhenqiu Lin, Susannah Bernheim, Arjun K Venkatesh, Lee A Fleisher, Michelle Schreiber, Lisa G Suter, Elizabeth W Triche

Student and Faculty Publications

OBJECTIVES: The extent to which care quality influenced outcomes for patients hospitalised with COVID-19 is unknown. Our objective was to determine if prepandemic hospital quality is associated with mortality among Medicare patients hospitalised with COVID-19.

DESIGN: This is a retrospective observational study. We calculated hospital-level risk-standardised in-hospital and 30-day mortality rates (risk-standardised mortality rates, RSMRs) for patients hospitalised with COVID-19, and correlation coefficients between RSMRs and pre-COVID-19 hospital quality, overall and stratified by hospital characteristics.

SETTING: Short-term acute care hospitals and critical access hospitals in the USA.

PARTICIPANTS: Hospitalised Medicare beneficiaries (Fee-For-Service and Medicare Advantage) age 65 and older hospitalised …

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 …

Health Economic Consequences Associated With Covid-19-Related Delay In Melanoma Diagnosis In Europe, Lara V Maul, Dagmar Jamiolkowski, Rebecca A Lapides, Alina M Mueller, Axel Hauschild, Claus Garbe, Paul Lorigan, Jeffrey E Gershenwald, Paolo Antonio Ascierto, Georgina V Long, Michael Wang-Evers, Richard A Scolyer, Babak Saravi, Matthias Augustin, Alexander A Navarini, Stefan Legge, István B Németh, Ágnes J Jánosi, Simone Mocellin, Anita Feller, Dieter Manstein, Alexander Zink, Julia-Tatjana Maul, Alessandra Buja, Kaustubh Adhikari, Elisabeth Roider

Student and Faculty Publications

IMPORTANCE: The COVID-19 pandemic resulted in delayed access to medical care. Restrictions to health care specialists, staff shortages, and fear of SARS-CoV-2 infection led to interruptions in routine care, such as early melanoma detection; however, premature mortality and economic burden associated with this postponement have not been studied yet.

OBJECTIVE: To determine the premature mortality and economic costs associated with suspended melanoma screenings during COVID-19 pandemic lockdowns by estimating the total burden of delayed melanoma diagnoses for Europe.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter economic evaluation used population-based data from patients aged at least 18 years with invasive primary cutaneous …

Differing Impacts Of The Covid-19 Pandemic On Farmers And Intermediaries: Insights Into The Ecuadorian Cocoa Value Chain, Guillermo Zambrano, Lina M Tennhardt, Moritz Egger, Karen Ramírez, Adriana Santos, Byron Moyano, Michael Curran

Student and Faculty Publications

The COVID-19 pandemic generated diverse impacts and responses in agricultural value chains worldwide. Cocoa is a key crop for Ecuadorian exports, and the analysis of effects the pandemic had on value chain actors contributes to the understanding of their individual capacities to coping with a major shock. The purpose of this study was to assess the number and severity of impacts and responses implemented by two links in the cocoa value chain to the pandemic, based on a survey of 158 cocoa farmers and 52 cocoa intermediaries from the main cocoa-producing provinces of the northern coast of Ecuador in 2021. …

Simvastatin In Critically Ill Patients With Covid-19, Thomas E Hills, Elizabeth Lorenzi, Lindsay R Berry, Murali Shyamsundar, Farah Al-Beidh, Djillali Annane, Yaseen Arabi, Diptesh Aryal, Carly Au, Abigail Beane, Zahra Bhimani, Marc Bonten, Charlotte A Bradbury, Frank M Brunkhorst, Aidan Burrell, Meredith Buxton, Carolyn S Calfee, Maurizio Cecconi, Allen C Cheng, Matthew E Cove, Michelle A Detry, Lise J Estcourt, Mark Fitzgerald, Ewan C Goligher, Herman Goossens, Cameron Green, Rashan Haniffa, David A Harrison, Madiha Hashmi, Alisa M Higgins, Christopher Horvat, David T Huang, Nao Ichihara, Deva Jayakumar, Peter S Kruger, François Lamontagne, Lamprini Lampro, Patrick R Lawler, John C Marshall, Alexina J Mason, Anna Mcglothlin, Shay Mcguinness, Zoe K Mcquilten, Bryan J Mcverry, Paul R Mouncey, Srinivas Murthy, Matthew D Neal, Alistair D Nichol, Cecilia M O'Kane, Rachael L Parke, Jane C Parker, Ebenezer Rabindrarajan, Luis F Reyes, Kathryn M Rowan, Hiroki Saito, Marlene Santos, Christina T Saunders, Christopher W Seymour, Manu Shankar-Hari, Pratik Sinha, B Taylor Thompson, Alexis F Turgeon, Anne M Turner, Frank Van De Veerdonk, Sebastian Weis, Ian S Young, Ryan Zarychanski, Roger J Lewis, Colin J Mcarthur, Derek C Angus, Scott M Berry, Lennie P G Derde, Steve A Webb, Anthony C Gordon, Daniel F Mcauley

Student and Faculty Publications

BACKGROUND: The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.

METHODS: In an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical …

Influenza Viral Infection Is A Risk Factor For Severe Illness In Covid-19 Patients: A Nationwide Population-Based Cohort Study, Jeong-Hwan Hwang, Yeon Seok You, Sang Woo Yeom, Min Gyu Lee, Jong-Hwan Lee, Min Gul Kim, Jong Seung Kim

Student and Faculty Publications

In order to prepare for the twindemic of influenza and SARS-CoV-2 infection, we investigated the association between influenza infection and subsequent severity of SARS-CoV-2 infection. A population-based nationwide cohort study was performed using data from the National Health Insurance Service (NHIS) in the Republic of Korea. This study included 274,126 individuals who underwent SARS-CoV-2 PCR testing between 20 January 2020 and 1 October 2020. Among these patients, 28,338 tested positive for SARS-CoV-2, and 4,003 of these individuals had a history of influenza. The control group was selected through 1:1 propensity score matching. In the group of 4,003 COVID-19-positive individuals with …

An Ace2 Decamer Viral Trap As A Durable Intervention Solution For Current And Future Sars-Cov, Hailong Guo, Bomsoo Cho, Paul R Hinton, Sijia He, Yongjun Yu, Ashwin Kumar Ramesh, Jwala Priyadarsini Sivaccumar, Zhiqiang Ku, Kristen Campo, Sarah Holland, Sameer Sachdeva, Christopher Mensch, Mohamed Dawod, Annalis Whitaker, Philip Eisenhauer, Allison Falcone, Rebekah Honce, Jason W Botten, Stephen F Carroll, Bruce A Keyt, Andrew W Womack, William R Strohl, Kai Xu, Ningyan Zhang, Zhiqiang An, Sha Ha, John W Shiver, Tong-Ming Fu

Student and Faculty Publications

The capacity of SARS-CoV-2 to evolve poses challenges to conventional prevention and treatment options such as vaccination and monoclonal antibodies, as they rely on viral receptor binding domain (RBD) sequences from previous strains. Additionally, animal CoVs, especially those of the SARS family, are now appreciated as a constant pandemic threat. We present here a new antiviral approach featuring inhalation delivery of a recombinant viral trap composed of ten copies of angiotensin-converting enzyme 2 (ACE2) fused to the IgM Fc. This ACE2 decamer viral trap is designed to inhibit SARS-CoV-2 entry function, regardless of viral RBD sequence variations as shown by …

Rapid, High Throughput, Automated Detection Of Sars-Cov-2 Neutralizing Antibodies Against Wuhan-Wt, Delta And Omicron Ba1, Ba2 Spike Trimers, Narayanaiah Cheedarla, Hans P Verkerke, Sindhu Potlapalli, Kaleb Benjamin Mclendon, Anamika Patel, Filipp Frank, William Henry O'Sick, Suneethamma Cheedarla, Tyler Jon Baugh, Gregory L Damhorst, Huixia Wu, Daniel Graciaa, Fuad Hudaib, David N Alter, Janetta Bryksin, Eric A Ortlund, Jeanette Guarner, Sara Auld, Sarita Shah, Wilbur Lam, Dawn Mattoon, Joseph M Johnson, David H Wilson, Madhav V Dhodapkar, Sean R Stowell, Andrew S Neish, John D Roback

Student and Faculty Publications

Traditional cellular and live-virus methods for detection of SARS-CoV-2 neutralizing antibodies (nAbs) are labor- and time-intensive, and thus not suited for routine use in the clinical lab to predict vaccine efficacy and natural immune protection. Here, we report the development and validation of a rapid, high throughput method for measuring SARS-CoV-2 nAbs against native-like trimeric spike proteins. This assay uses a blockade of human angiotensin converting enzyme 2 (hACE-2) binding (BoAb) approach in an automated digital immunoassay on the Quanterix HD-X platform. BoAb assays using Wuhan-WT (vaccine strain), delta (B.1.167.2), omicron BA1 and BA2 variant viral strains showed strong correlation …

Comparison Between Viral Vector And Mrna Based Covid-19 Vaccination In Prevalence And Severity Of Regional Immune Reactions, And 18f-Fdg Pet/Ct Features, Narjess Ayati, Scott Evans, S Rasoul Zakavi, Simon M Gruenewald

Student and Faculty Publications

Objective(s):

The coronavirus pandemic caused by SARS-CoV-2 commenced in late 2019, and global wide vaccination appears to be the only reasonable solution to fight this dreadful virus. There are two main types of COVID-19 immunization using viral vector and mRNA-based vaccines. However, the impact of each of type on 18F-FDG PET/CT needs to be accurately assessed. This study aimed to compare the 18F-FDG PET/CT features of these two types of COVID-19 vaccines.

Methods:

A total of 188 patients referred for 18F-FDG PET/CT with a recent history of either BioNTech/Pfizer or AstraZeneca COVID-19 vaccination, and a control group of 40 patients …

Neuroprotective Agents With Therapeutic Potential For Covid-19, César A Zaa, Clara Espitia, Karen L Reyes-Barrera, Zhiqiang An, Marco A Velasco-Velázquez

Student and Faculty Publications

COVID-19 patients can exhibit a wide range of clinical manifestations affecting various organs and systems. Neurological symptoms have been reported in COVID-19 patients, both during the acute phase of the illness and in cases of long-term COVID. Moderate symptoms include ageusia, anosmia, altered mental status, and cognitive impairment, and in more severe cases can manifest as ischemic cerebrovascular disease and encephalitis. In this narrative review, we delve into the reported neurological symptoms associated with COVID-19, as well as the underlying mechanisms contributing to them. These mechanisms include direct damage to neurons, inflammation, oxidative stress, and protein misfolding. We further investigate …

Cancer Patients' Preferences And Perceptions Of Advantages And Disadvantages Of Telehealth Visits During The Covid-19 Pandemic, Deepika Kumar, Nancy Gordon, Constanza Zamani, Tammy Sheehan, Ernesto Martin, Olga Egorova, Jessica Payne, Tatjana Kolevska, Elad Neeman, Raymond Liu

Student and Faculty Publications

PURPOSE: We aimed to ascertain oncology patients' perceptions of telehealth versus in-person (IP) visits for different types of clinical encounters.

METHODS: We surveyed adults undergoing cancer treatment at Kaiser Permanente Northern California infusion centers between November 2021 and May 2022 using a self-administered questionnaire. Patients were asked about visit modality preferences (video, phone, and IP) for six types of clinical discussions, overall advantages and disadvantages of telehealth (video or phone) versus IP modalities, and barriers to video visit use.

RESULTS: The 839 patients who completed surveys in English were 63% female; median age 63 years; 64% White; and 73% college-educated …

Intravenous Aviptadil And Remdesivir For Treatment Of Covid-19-Associated Hypoxaemic Respiratory Failure In The Usa (Tesico): A Randomised, Placebo-Controlled Trial, Samuel M Brown, Christina E Barkauskas, Birgit Grund, Shweta Sharma, Andrew N Phillips, Lindsay Leither, Ithan D Peltan, Michael Lanspa, Daniel L Gilstrap, Ahmad Mourad, Kathleen Lane, Jeremy R Beitler, Alexis L Serra, Ivan Garcia, Eyad Almasri, Mohamed Fayed, Kinsley Hubel, Estelle S Harris, Elizabeth A Middleton, Macy A G Barrios, Kusum S Mathews, Neha N Goel, Samuel Acquah, Jarrod Mosier, Cameron Hypes, Elizabeth Salvagio Campbell, Akram Khan, Catherine L Hough, Jennifer G Wilson, Joseph E Levitt, Abhijit Duggal, Siddharth Dugar, Andrew J Goodwin, Charles Terry, Peter Chen, Sam Torbati, Nithya Iyer, Uriel S Sandkovsky, Nicholas J Johnson, Bryce R H Robinson, Michael A Matthay, Neil R Aggarwal, Ivor S Douglas, Jonathan D Casey, Manuel Hache-Marliere, J Georges Youssef, William Nkemdirim, Brad Leshnower, Omar Awan, Sonal Pannu, Darragh Shane O'Mahony, Prasad Manian, J W Awori Hayanga, Glenn W Wortmann, Bruno M Tomazini, Robert F Miller, Jens-Ulrik Jensen, Daniel D Murray, Nina A Bickell, Jigna Zatakia, Sarah Burris, Elizabeth S Higgs, Ven Natarajan, Robin L Dewar, Adam Schechner, Nayon Kang, Alejandro Arenas-Pinto, Fleur Hudson, Adit A Ginde, Wesley H Self, Angela J Rogers, Cathryn F Oldmixon, Haley Morin, Adriana Sanchez, Amy C Weintrob, Alexandre Biasi Cavalcanti, Anne Davis-Karim, Nicole Engen, Eileen Denning, B Taylor Thompson, Annetine C Gelijns, Virginia Kan, Victoria J Davey, Jens D Lundgren, Abdel G Babiker, James D Neaton, H Clifford Lane

Student and Faculty Publications

BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure.

METHODS: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly …

Social Risks, Social Needs, And Attitudes Toward Social Health Screening 1 Year Into The Covid-19 Pandemic: Survey Of Adults In An Integrated Health Care Delivery System, Nancy P Gordon, Carmen Byker Shanks, Richard W Grant

Student and Faculty Publications

Introduction Information about demographic differences in social risks, needs, and attitudes toward social health screening in non-highly vulnerable adult populations is lacking. Methods The authors analyzed data for 2869 Kaiser Permanente Northern California non-Medicaid-covered members aged 35 to 85 who responded to a 2021 English-only mailed/online survey. The survey covered 7 social risk and 11 social needs domains and attitudes toward social health screening. The authors used data weighted to the Kaiser Permanente Northern California membership to estimate prevalence of risks, needs, and screening receptivity in the overall population, by race/ethnicity (White, Black, Latinx, Asian American/Pacific Islander) and age (35-65 …

Clinically Stable Covid-19 Patients Presenting To Acute Unscheduled Episodic Care Venues Have Increased Risk Of Hospitalization: Secondary Analysis Of A Randomized Control Trial, Joseph Bledsoe, Scott C Woller, Maria Brooks, Frank C Sciurba, Jerry A Krishnan, Deborah Martin, Peter Hou, Janet Y Lin, Andrei Kindzelski, Eileen Handberg, Bridget-Anne Kirwan, Elaine Zaharris, Lauren Castro, Nancy L Shapiro, Carl J Pepine, Sarah Majercik, Zhuxuan Fu, Yongqi Zhong, Vidya Venugopal, Yu-Hsuan Lai, Paul M Ridker, Jean M Connors

Student and Faculty Publications

BACKGROUND: Assessment for risks associated with acute stable COVID-19 is important to optimize clinical trial enrollment and target patients for scarce therapeutics. To assess whether healthcare system engagement location is an independent predictor of outcomes we performed a secondary analysis of the ACTIV-4B Outpatient Thrombosis Prevention trial.

METHODS: A secondary analysis of the ACTIV-4B trial that was conducted at 52 US sites between September 2020 and August 2021. Participants were enrolled through acute unscheduled episodic care (AUEC) enrollment location (emergency department, or urgent care clinic visit) compared to minimal contact (MC) enrollment (electronic contact from test center lists of positive …

Higher Dose Corticosteroids In Patients Admitted To Hospital With Covid-19 Who Are Hypoxic But Not Requiring Ventilatory Support (Recovery): A Randomised, Controlled, Open-Label, Platform Trial, Recovery Collaborative Group

Student and Faculty Publications

BACKGROUND: Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group.

METHODS: This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation

FINDINGS: Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen …

Outcomes Following Extracorporeal Membrane Oxygenation For Severe Covid-19 In Pregnancy Or Post Partum, John J Byrne, Amir A Shamshirsaz, Alison G Cahill, Mark A Turrentine, Angela R Seasely, Joe Eid, Caroline E Rouse, Michael Richley, Nandini Raghuraman, Mariam Naqvi, Yasser Y El-Sayed, Martina L Badell, Cece Cheng, James Liu, Emily H Adhikari, Soha S Patel, Erika R O'Neil, Patrick S Ramsey

Student and Faculty Publications

IMPORTANCE: Existing reports of pregnant patients with COVID-19 disease who require extracorporeal membrane oxygenation (ECMO) are limited, with variable outcomes noted for the maternal-fetal dyad.

OBJECTIVE: To examine maternal and perinatal outcomes associated with ECMO used for COVID-19 with respiratory failure during pregnancy.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective multicenter cohort study examined pregnant and postpartum patients who required ECMO for COVID-19 respiratory failure at 25 hospitals across the US. Eligible patients included individuals who received care at one of the study sites, were diagnosed with SARS-CoV-2 infection during pregnancy or up to 6 weeks post partum by positive nucleic …

Gwas And Meta-Analysis Identifies 49 Genetic Variants Underlying Critical Covid-19, Erola Pairo-Castineira, Konrad Rawlik, Andrew D Bretherick, Ting Qi, Yang Wu, Isar Nassiri, Glenn A Mcconkey, Marie Zechner, Lucija Klaric, Fiona Griffiths, Wilna Oosthuyzen, Athanasios Kousathanas, Anne Richmond, Jonathan Millar, Clark D Russell, Tomas Malinauskas, Ryan Thwaites, Kirstie Morrice, Sean Keating, David Maslove, Alistair Nichol, Malcolm G Semple, Julian Knight, Manu Shankar-Hari, Charlotte Summers, Charles Hinds, Peter Horby, Lowell Ling, Danny Mcauley, Hugh Montgomery, Peter J M Openshaw, Colin Begg, Timothy Walsh, Albert Tenesa, Carlos Flores, José A Riancho, Augusto Rojas-Martinez, Pablo Lapunzina, Genomicc Investigators, Scourge Consortium, Isaricc Investigators, 23andme Covid-19 Team, Jian Yang, Chris P Ponting, James F Wilson, Veronique Vitart, Malak Abedalthagafi, Andre D Luchessi, Esteban J Parra, Raquel Cruz, Angel Carracedo, Angie Fawkes, Lee Murphy, Kathy Rowan, Alexandre C Pereira, Andy Law, Benjamin Fairfax, Sara Clohisey Hendry, J Kenneth Baillie

Student and Faculty Publications

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a …

Sars-Cov-2 Serostatus And Covid-19 Illness Characteristics By Variant Time Period In Non-Hospitalized Children And Adolescents, Sarah E Messiah, Michael D Swartz, Rhiana A Abbas, Yashar Talebi, Harold W Kohl, Melissa Valerio-Shewmaker, Stacia M Desantis, Ashraf Yaseen, Steven H Kelder, Jessica A Ross, Lindsay N Padilla, Michael O Gonzalez, Leqing Wu, David Lakey, Jennifer A Shuford, Stephen J Pont, Eric Boerwinkle

Student and Faculty Publications

OBJECTIVE: to describe COVID-19 illness characteristics, risk factors, and SARS-CoV-2 serostatus by variant time period in a large community-based pediatric sample.

DESIGN: Data were collected prospectively over four timepoints between October 2020 and November 2022 from a population-based cohort ages 5 to 19 years old.

SETTING: State of Texas, USA.

PARTICIPANTS: Participants ages 5 to 19 years were recruited from large pediatric healthcare systems, Federally Qualified Healthcare Centers, urban and rural clinical practices, health insurance providers, and a social media campaign.

EXPOSURE: SARS-CoV-2 infection.

MAIN OUTCOME(S) AND MEASURE(S): SARS-CoV-2 antibody status was assessed by the Roche Elecsys

RESULTS: Over half …

Metabolic Dysregulation Impairs Lymphocyte Function During Severe Sars-Cov-2 Infection, Sanjeev Gurshaney, Anamaria Morales-Alvarez, Kevin Ezhakunnel, Andrew Manalo, Thien-Huong Huynh, Jun-Ichi Abe, Nhat-Tu Le, Daniela Weiskopf, Alessandro Sette, Daniel S Lupu, Stephen J Gardell, Hung Nguyen

Student and Faculty Publications

Cellular metabolic dysregulation is a consequence of SARS-CoV-2 infection that is a key determinant of disease severity. However, how metabolic perturbations influence immunological function during COVID-19 remains unclear. Here, using a combination of high-dimensional flow cytometry, cutting-edge single-cell metabolomics, and re-analysis of single-cell transcriptomic data, we demonstrate a global hypoxia-linked metabolic switch from fatty acid oxidation and mitochondrial respiration towards anaerobic, glucose-dependent metabolism in CD8+Tc, NKT, and epithelial cells. Consequently, we found that a strong dysregulation in immunometabolism was tied to increased cellular exhaustion, attenuated effector function, and impaired memory differentiation. Pharmacological inhibition of mitophagy with mdivi-1 reduced excess glucose …

Covid-19 And Employee Job Performance Trajectories: The Moderating Effect Of Different Sources Of Status, Xin Liu, Xiaoming Zheng, Byron Y Lee, Yu Yu, Mengyi Zhang

Student and Faculty Publications

This study investigates the impact of the COVID-19 pandemic on employee job performance trajectories, and further examines the moderating effects of different sources of status. Drawing from event system theory (EST), we propose that employee job performance decreases upon COVID-19 onset, but gradually increases during the postonset period. Furthermore, we argue that status from society, occupation, and workplace functions to moderate such performance trajectories. We test our hypotheses with a unique dataset of 708 employees that combines survey responses and job performance archival data over 21 consecutive months (10,808 observations) spanning the preonset, onset, and postonset periods of the initial …

Institutional Strategies To Maintain And Grow Imaging Research During The Covid-19 Pandemic, Mai-Lan Ho, Corey W Arnold, Summer J Decker, John D Hazle, Elizabeth A Krupinski, David A Mankoff

Student and Faculty Publications

Understanding imaging research experiences, challenges, and strategies for academic radiology departments during and after COVID-19 is critical to prepare for future disruptive events. We summarize key insights and programmatic initiatives at major academic hospitals across the world, based on literature review and meetings of the Radiological Society of North America Vice Chairs of Research (RSNA VCR) group. Through expert discussion and case studies, we provide suggested guidelines to maintain and grow radiology research in the postpandemic era.

The P323l Substitution In The Sars-Cov-2 Polymerase (Nsp12) Confers A Selective Advantage During Infection, Hannah Goldswain, Xiaofeng Dong, Rebekah Penrice-Randal, Muhannad Alruwaili, Ghada T Shawli, Tessa Prince, Maia Kavanagh Williamson, Jayna Raghwani, Nadine Randle, Benjamin Jones, I'Ah Donovan-Banfield, Francisco J Salguero, Julia A Tree, Yper Hall, Catherine Hartley, Maximilian Erdmann, James Bazire, Tuksin Jearanaiwitayakul, Malcolm G Semple, Peter J M Openshaw, J Kenneth Baillie, Isaric4c Investigators, Stevan R Emmett, Paul Digard, David A Matthews, Lance Turtle, Alistair C Darby, Andrew D Davidson, Miles W Carroll, Julian A Hiscox

Student and Faculty Publications

BACKGROUND: The mutational landscape of SARS-CoV-2 varies at the dominant viral genome sequence and minor genomic variant population. During the COVID-19 pandemic, an early substitution in the genome was the D614G change in the spike protein, associated with an increase in transmissibility. Genomes with D614G are accompanied by a P323L substitution in the viral polymerase (NSP12). However, P323L is not thought to be under strong selective pressure.

RESULTS: Investigation of P323L/D614G substitutions in the population shows rapid emergence during the containment phase and early surge phase during the first wave. These substitutions emerge from minor genomic variants which become dominant …

Clinical Characteristics And Cause Of Death Among Hospitalized Decedents With Cancer And Covid-19, Dereddi Raja Reddy, John A Cuenca, Joshua Botdorf, Mayoora Muthu, Ankit Hanmandlu, Robert Wegner, John Crommett, Cristina Gutierrez, Nisha Rathi, Bilja Sajith, Mark Knafl, Hussein A Abbas, Scott E Woodman, Joseph L Nates

Student and Faculty Publications

There is scant information on the clinical progression, end-of-life decisions, and cause of death of patients with cancer diagnosed with COVID-19. Therefore, we conducted a case series of patients admitted to a comprehensive cancer center who did not survive their hospitalization. To determine the cause of death, 3 board-certified intensivists reviewed the electronic medical records. Concordance regarding cause of death was calculated. Discrepancies were resolved through a joint case-by-case review and discussion among the 3 reviewers. During the study period, 551 patients with cancer and COVID-19 were admitted to a dedicated specialty unit; among them, 61 (11.6%) were nonsurvivors. Among …

Identification Of And Mechanistic Insights Into Sars-Cov-2 Main Protease Non-Covalent Inhibitors: An In-Silico Study, Jian-Xin Shen, Wen-Wen Du, Yuan-Ling Xia, Zhi-Bi Zhang, Ze-Fen Yu, Yun-Xin Fu, Shu-Qun Liu

Student and Faculty Publications

The indispensable role of the SARS-CoV-2 main protease (Mpro) in the viral replication cycle and its dissimilarity to human proteases make Mpro a promising drug target. In order to identify the non-covalent Mpro inhibitors, we performed a comprehensive study using a combined computational strategy. We first screened the ZINC purchasable compound database using the pharmacophore model generated from the reference crystal structure of Mpro complexed with the inhibitor ML188. The hit compounds were then filtered by molecular docking and predicted parameters of drug-likeness and pharmacokinetics. The final molecular dynamics (MD) simulations identified three effective candidate inhibitors (ECIs) capable of maintaining …

Risks Of Mortality And Severe Coronavirus Disease 19 (Covid-19) Outcomes In Patients With Or Without Systemic Lupus Erythematosus, Sebastian Bruera, Xiudong Lei, Hui Zhao, Jinoos Yazdany, Mariana Chavez-Macgregor, Sharon H Giordano, Maria E Suarez-Almazor

Student and Faculty Publications

OBJECTIVES: We compared the outcomes of patients with or without systemic lupus erythematosus (SLE) who were diagnosed with coronavirus disease 19 (COVID-19) and evaluated factors within patients with SLE associated with severe outcomes.

METHODS: This retrospective cohort study used the deidentified Optum COVID-19 electronic health record dataset to identify patients with COVID-19 from 1/1/2020 to 31/12/2020. Cases with SLE were matched with general controls at a ratio of 1:10 by age, sex, race and ethnicity and COVID-19 diagnosis date. Outcomes included 30-day mortality, mechanical ventilation, hospitalisation and intensive care unit admission. We evaluated the relationship between COVID-19-related outcomes and SLE …

The Orf7a Protein Of Sars-Cov-2 Initiates Autophagy And Limits Autophagosome-Lysosome Fusion Via Degradation Of Snap29 To Promote Virus Replication, Peili Hou, Xuefeng Wang, Hongmei Wang, Tiecheng Wang, Zhangping Yu, Chunqing Xu, Yudong Zhao, Wenqi Wang, Yong Zhao, Fengyun Chu, Huasong Chang, Hongchao Zhu, Jiahui Lu, Fuzhen Zhang, Xue Liang, Xingyu Li, Song Wang, Yuwei Gao, Hongbin He

Student and Faculty Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is closely related to various cellular aspects associated with autophagy. However, how SARS-CoV-2 mediates the subversion of the macroautophagy/autophagy pathway remains largely unclear. In this study, we demonstrate that overexpression of the SARS-CoV-2 ORF7a protein activates LC3-II and leads to the accumulation of autophagosomes in multiple cell lines, while knockdown of the viral ORF7a gene via shRNAs targeting ORF7a sgRNA during SARS-CoV-2 infection decreased autophagy levels. Mechanistically, the ORF7a protein initiates autophagy via the AKT-MTOR-ULK1-mediated pathway, but ORF7a limits the progression of autophagic flux by activating CASP3 (caspase 3) to cleave the …

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 …

Population-Based Assessment Of The Burden Of Covid-19 Infection In African Countries: A First-Year Report Card And Public Health Implications, Osaro Mgbere, Ogbonna Collins Nwabuko, Olajumoke A Olateju, Omolola E Adepoju, Winston Liaw, Charles Darkoh, Ekere James Essien

Student and Faculty Publications

BACKGROUND: The COVID-19 pandemic constitutes a global health threat and poses a major burden on the African continent. We assessed the real-world burden of COVID-19 infection in African Union (AU) member states to determine the distributional patterns of epidemiological measures during the first 1 year of the pandemic.

METHODS: This retrospective cross-sectional study utilized COVID-19 data from publicly available data repositories of the African Center for Disease Control and Prevention and

RESULTS: A total of 3.21 million cases were reported during the 1-year period, with 2.6 million recoveries, 536,784 cases remaining active, and 77,486 deaths. Most countries (49.1%,

CONCLUSION: Understanding …