Medicine and Health Sciences Commons^™

Igg3 Subclass Antibodies Recognize Antigenically Drifted Influenza Viruses And Sars-Cov-2 Variants Through Efficient Bivalent Binding, Marcus J. Bolton, Jefferson J.S. Santos, Claudia P. Arevalo, Trevor Griesman, Megan Watson, Shuk Hang Li, Paul Bates, Holly Ramage, Patrick C. Wilson, Scott E. Hensley

Department of Microbiology and Immunology Faculty Papers

The constant domains of antibodies are important for effector functions, but less is known about how they can affect binding and neutralization of viruses. Here, we evaluated a panel of human influenza virus monoclonal antibodies (mAbs) expressed as IgG1, IgG2, or IgG3. We found that many influenza virus-specific mAbs have altered binding and neutralization capacity depending on the IgG subclass encoded and that these differences result from unique bivalency capacities of the subclasses. Importantly, subclass differences in antibody binding and neutralization were greatest when the affinity for the target antigen was reduced through antigenic mismatch. We found that antibodies expressed …

Nailfold Videocapillaroscopic Alterations As Markers Of Microangiopathy In Covid-19 Patients, Roberta Gualtierotti, Sharon E. Fox, Fernanda Da Silva Lameira, Andrea Giachi, Luca Valenti, Maria Orietta Borghi, Pier Luigi Meroni, Massimo Cugno, Flora Peyvandi

School of Medicine Faculty Publications

Nailfold videocapillaroscopic alterations have been described in COVID-19, but their correlations with biomarkers of inflammation, coagulation and endothelial perturbation are still unclear, and no information is available on nailfold histopathology. Nailfold videocapillaroscopy was performed on fifteen patients with COVID-19 in Milan, Italy and the signs of microangiopathy were correlated with plasma biomarkers of inflammation (C reactive protein [CRP], ferritin), coagulation (D-dimer, fibrinogen), endothelial perturbation (Von Willebrand factor [VWF]) and angiogenesis (vascular endothelial growth factor [VEGF]) along with genetic drivers of COVID-19 susceptibility. Histopathological analysis of autoptic nailfold excisions was performed on fifteen patients who died for COVID-19 in New Orleans, …

A Computationally Designed Ace2 Decoy Has Broad Efficacy Against Sars-Cov-2 Omicron Variants And Related Viruses In Vitro And In Vivo, Brandon Havranek, Graeme Walker Lindsey, Yusuke Higuchi, Yumi Itoh, Tatsuya Suzuki, Toru Okamoto, Atsushi Hoshino, Erik Procko, Shahidul M. Islam

SKMC Student Presentations and Publications

SARS-CoV-2, especially B.1.1.529/omicron and its sublineages, continues to mutate to evade monoclonal antibodies and antibodies elicited by vaccination. Affinity-enhanced soluble ACE2 (sACE2) is an alternative strategy that works by binding the SARS-CoV-2 S protein, acting as a 'decoy' to block the interaction between the S and human ACE2. Using a computational design strategy, we designed an affinity-enhanced ACE2 decoy, FLIF, that exhibited tight binding to SARS-CoV-2 delta and omicron variants. Our computationally calculated absolute binding free energies (ABFE) between sACE2:SARS-CoV-2 S proteins and their variants showed excellent agreement to binding experiments. FLIF displayed robust therapeutic utility against a broad range …

Sars-Cov-2 Restructures Host Chromatin Architecture, Ruoyu Wang, Joo-Hyung Lee, Jieun Kim, Feng Xiong, Lana Al Hasani, Yuqiang Shi, Erin N Simpson, Xiaoyu Zhu, Yi-Ting Chen, Pooja Shivshankar, Joanna Krakowiak, Yanyu Wang, David M Gilbert, Xiaoyi Yuan, Holger K Eltzschig, Wenbo Li

Journal Articles

Some viruses restructure host chromatin, influencing gene expression, with implications for disease outcome. Whether this occurs for SARS-CoV-2, the virus causing COVID-19, is largely unknown. Here we characterized the 3D genome and epigenome of human cells after SARS-CoV-2 infection, finding widespread host chromatin restructuring that features widespread compartment A weakening, A-B mixing, reduced intra-TAD contacts and decreased H3K27ac euchromatin modification levels. Such changes were not found following common-cold-virus HCoV-OC43 infection. Intriguingly, the cohesin complex was notably depleted from intra-TAD regions, indicating that SARS-CoV-2 disrupts cohesin loop extrusion. These altered 3D genome/epigenome structures correlated with transcriptional suppression of interferon response genes …

Sars-Cov-2 Restructures Host Chromatin Architecture, Ruoyu Wang, Joo-Hyung Lee, Jieun Kim, Feng Xiong, Lana Al Hasani, Yuqiang Shi, Erin N Simpson, Xiaoyu Zhu, Yi-Ting Chen, Pooja Shivshankar, Joanna Krakowiak, Yanyu Wang, David M Gilbert, Xiaoyi Yuan, Holger K Eltzschig, Wenbo Li

Journal Articles

Some viruses restructure host chromatin, influencing gene expression, with implications for disease outcome. Whether this occurs for SARS-CoV-2, the virus causing COVID-19, is largely unknown. Here we characterized the 3D genome and epigenome of human cells after SARS-CoV-2 infection, finding widespread host chromatin restructuring that features widespread compartment A weakening, A-B mixing, reduced intra-TAD contacts and decreased H3K27ac euchromatin modification levels. Such changes were not found following common-cold-virus HCoV-OC43 infection. Intriguingly, the cohesin complex was notably depleted from intra-TAD regions, indicating that SARS-CoV-2 disrupts cohesin loop extrusion. These altered 3D genome/epigenome structures correlated with transcriptional suppression of interferon response genes …

Design And Preclinical Evaluation Of A Universal Sars-Cov-2 Mrna Vaccine, Jane Qin, Ju Hyeong Jeon, Jiangsheng Xu, Laura Katherine Langston, Ramesh Marasini, Stephanie Mou, Brian Montoya, Carolina R Melo-Silva, Hyo Jin Jeon, Tianyi Zhu, Luis J. Sigal, Renhuan Xu, Huabin Zhu

Department of Microbiology and Immunology Faculty Papers

Because of the rapid mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective vaccine against SARS-CoV-2 variants is needed to prevent coronavirus disease 2019 (COVID-19). T cells, in addition to neutralizing antibodies, are an important component of naturally acquired protective immunity, and a number of studies have shown that T cells induced by natural infection or vaccination contribute significantly to protection against several viral infections including SARS-CoV-2. However, it has never been tested whether a T cell-inducing vaccine can provide significant protection against SARS-CoV-2 infection in the absence of preexisting antibodies. In this study, we designed and evaluated …

An Unusual Case Of Hemophagocytic Lymphohistiocytosis Associated With Mycobacterium Chimaera Or Large-Cell Neuroendocrine Carcinoma, Tejaswi Venigalla, Sheila Kalathil, Meena Bansal, Mark Morginstin, Vinicius Jorge, Patricia Perosio

Einstein Health Papers

Hemophagocytic lymphohistiocytosis (HLH) is a rare and very dangerous condition characterized by abnormal activation of the immune system, causing hemophagocytosis, inflammation, and potentially widespread organ damage. The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity, is most commonly seen in children. Secondary HLH is commonly associated with infections, malignancies, and rheumatologic disorders. Most current information on diagnosis and treatment is based on pediatric populations. HLH is a disease that should be diagnosed and treated promptly, otherwise it is fatal. Treatment is directed at treating the triggering disorder, along with symptomatic treatment with dexamethasone and etoposide. We present a 56-year-old …

The Pathogenesis Of Covid-19: Hypercoagulation And D-Dimer In Thrombotic Complications, Leonid Dubey, Halyna Lytvyn, Olha Dorosh, Nataliya Dubey, Olena Kozlova, Michal Pruc, Nina Kubikowska, Lukasz Szarpak, Kavita Batra, Francesco Chirico, Gabriella Nucera, Svitlana Doan, Uljana Shevtsiv

School of Medicine Faculty Publications

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a new coronavirus disease (COVID-19), which is highly contagious and its pathogenesis has not been fully elucidated. In COVID-19, the inflammation and blood coagulation systems are excessively activated. SARS-CoV- 2 damages endothelial cells and pneumocytes, which leads to disruption of hemostasis in SARS. Thromboembolism is the main cause of mortality in patients with COVID-19. Clots, including pulmonary embolism (PE) and deep vein thrombosis (DVT), ranging from minor to fatal complications of the SARS-CoV-2 infection are known. Individuals with pre-existing diseases are more susceptible to the development of blood clots and poor outcomes. …

Endogenous Mirna-Based Innate-Immunity Against Sars-Cov-2 Invasion Of The Brain, Walter J. Lukiw, Aileen I. Pogue

School of Medicine Faculty Publications

The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger RNA (mRNA) possessing a 5′-methyl cap (m7GpppN), a 3′- and 5′-untranslated region (3′-UTR, 5′-UTR), and a poly-adenylated (poly-A+) tail. As such, the SARS-CoV-2 ssvRNA is susceptible to targeting by small non-coding RNA (sncRNA) and/or microRNA (miRNA), as well as neutralization and/or inhibition of its infectivity via the human body’s natural complement of about ~2650 miRNA species. Depending on host cell and tissue …

Development Of A Novel Mathematical Model That Explains Sars-Cov-2 Infection Dynamics In Caco-2 Cells, Vladimir Staroverov, Stepan Nersisyan, Alexei Galatenko, Dmitriy Alekseev, Sofya Lukashevich, Fedor Ployakov, Nikita Anisimov, Alexander Tonevitsky

COVID-19 Papers, Posters, and Presentations

Mathematical modeling is widely used to study within-host viral dynamics. However, to the best of our knowledge, for the case of SARS-CoV-2 such analyses were mainly conducted with the use of viral load data and for the wild type (WT) variant of the virus. In addition, only few studies analyzed models for in vitro data, which are less noisy and more reproducible. In this work we collected multiple data types for SARS-CoV-2-infected Caco-2 cell lines, including infectious virus titers, measurements of intracellular viral RNA, cell viability data and percentage of infected cells for the WT and Delta variants. We showed …

Hyaluronan In The Pathogenesis Of Acute And Post-Acute Covid-19 Infection, Henry W Barnes, Sally Demirdjian, Naomi L Haddock, Gernot Kaber, Hunter A Martinez, Nadine Nagy, Harry Karmouty-Quintana, Paul L Bollyky

Journal Articles

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged as the cause of a global pandemic. Infection with SARS-CoV-2 can result in COVID-19 with both acute and chronic disease manifestations that continue to impact many patients long after the resolution of viral replication. There is therefore great interest in understanding the host factors that contribute to COVID-19 pathogenesis. In this review, we address the role of hyaluronan (HA), an extracellular matrix polymer with roles in inflammation and cellular metabolism, in COVID-19 and critically evaluate the hypothesis that HA promotes COVID-19 pathogenesis. We first provide a brief overview of COVID-19 infection. …

Safety Of Adenosine For The Treatment Of Supraventricular Tachycardia In Hospitalized Patients With Covid-19 Pneumonia, T. Zivan, Ramon L Ruiz, Alexandre Martinez, Behzad B. Pavri

Department of Medicine Faculty Papers

Coronavirus disease 2019 (COVID-19) is associated with pulmonary involvement and cardiac arrhythmias, including supraventricular tachycardia (SVT). Adenosine is commonly used to treat SVT and is generally safe, but is rarely associated with bronchospasm. There are no data regarding the safety of adenosine use in patients with COVID-19 pneumonia and physicians may hesitate to use it in such patients. We surveyed resident physicians and cardiology attendings regarding their level of comfort in administering adenosine to hospitalized COVID-19 patients. We compared a study group of 42 COVID-19 hospitalized patients who received adenosine for SVT to a matched (for age, sex, and co-morbidities) …

A Rare Case Of Covid Encephalitis In A Vaccinated Patient, Christian Pena, Hari Movva, Hector Arredondo, Alberto Pena, Erik Hinojosa, Michael Rotko, Jorge Nadal, Michelle Lopez

MEDI 9331 Scholarly Activities Clinical Years

Background and Purpose: SARS-CoV-2 infection is known to cause primarily respiratory symptoms, however, neurological disorders such as anosmia and stroke have been seen. Encephalitis is a rare complication of COVID-19 with a reported incidence of less than 1%¹. Most patients develop both COVID-19 symptoms and encephalitis symptoms during the same period¹. In addition, the majority of reports are from patients with no prior vaccination. Here, we present a case of encephalitis 2 weeks after mild COVID-19 in a fully vaccinated male.

Case Presentation: A 68-year-old Hispanic male was brought to the ED due to new onset gaze deviation, generalized tonic …

Covid-19 Vaccine Hesitancy In Asean: Insights From A Multi-Wave Survey Database From July 2020 To March 2021, Kenneth Y. Hartigan-Go, Ronald U. Mendoza, Madeline Mae A. Ong, Jurel K. Yap

Ateneo School of Medicine and Public Health Publications

Objectives

Early studies on COVID-19 vaccine hesitancy showed varied intensity across countries, which was linked to various factors such as socio-economic conditions, information sources, and issues of trust in government, scientific experts, and the health sector. This study aims to evaluate the determinants of vaccine hesitancy to offer insights into the strategies that may be successful in designing communications campaigns for enhanced vaccination uptake.

Methods

Through logistic regression, this study examines correlates of survey data from five Southeast Asian countries, namely Indonesia (ID), Malaysia (MY), Philippines (PH), Thailand (TH), Vietnam (VN) collected by the Massachusetts Institute of Technology Initiative on …

A Longitudinal Seroepidemiology Study To Evaluate Antibody Response To Sars-Cov-2 Virus Infection And Vaccination In Children In Calgary, Canada From July 2020 To April 2022: Alberta Covid-19 Childhood Cohort (Ab3c) Study, Emily J Doucette, Joslyn Gray, Kevin Fonseca, Carmen Charlton, Jamil N Kanji, Graham Tipples, Susan Kuhn, Jessica Dunn, Payton Sayers, Nicola Symonds, Guosong Wu, Stephen B Freedman, James D Kellner

Journal Articles

BACKGROUND: Measurement of SARS-CoV-2 antibody seropositivity is important to accurately understand exposure to infection and/or vaccination in specific populations. This study aimed to estimate the serologic response to SARS-CoV-2 virus infection and vaccination in children in Calgary, Alberta over a two-year period.

METHODS: Children with or without prior SARS-CoV-2 infections, were enrolled in Calgary, Canada in 2020. Venous blood was sampled 4 times from July 2020 to April 2022 for SARS-CoV-2 nucleocapsid and spike antibodies. Demographic and clinical information was obtained including SARS-CoV-2 testing results and vaccination records.

RESULTS: 1035 children were enrolled and 88.9% completed all 4 visits; median …