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Sars-Coronavirus-2 Nucleocapsid Protein Measured In Blood Using A Simoa Ultra-Sensitive Immunoassay Differentiates Covid-19 Infection With High Clinical Sensitivity., Dandan Shan, Eicke Latz, Andrew J. Ball 2020 Quanterix Corporation

Sars-Coronavirus-2 Nucleocapsid Protein Measured In Blood Using A Simoa Ultra-Sensitive Immunoassay Differentiates Covid-19 Infection With High Clinical Sensitivity., Dandan Shan, Eicke Latz, Andrew J. Ball

University of Massachusetts Medical School Faculty Publications

The COVID-19 pandemic continues to have an unprecedented impact on societies and economies worldwide. Despite rapid advances in diagnostic test development and scale-up, there remains an ongoing need for SARS-CoV-2 tests which are highly sensitive, specific, minimally invasive, cost-effective and scalable for broad testing and surveillance. Here we report development of a highly sensitive single molecule array (Simoa) immunoassay on the automated HD-X platform for the detection of SARS-CoV-2 Nucleocapsid protein (N-protein) in venous and capillary blood (fingerstick). In pre-pandemic and clinical sample sets, the assay has 100% specificity and 97.4% sensitivity for serum / plasma samples. The limit of ...


Host Immunity Increases Mycobacterium Tuberculosis Reliance On Cytochrome Bd Oxidase, Yi Cai, Eleni Jaecklein, Jared Mackenzie, Kadamba Papavinasasundaram, Michigan State University, Xinchun Chen, Africa Health Research Institute, Christopher M. Sassetti 2020 Shenzhen University

Host Immunity Increases Mycobacterium Tuberculosis Reliance On Cytochrome Bd Oxidase, Yi Cai, Eleni Jaecklein, Jared Mackenzie, Kadamba Papavinasasundaram, Michigan State University, Xinchun Chen, Africa Health Research Institute, Christopher M. Sassetti

University of Massachusetts Medical School Faculty Publications

In order to sustain a persistent infection, Mycobacterium tuberculosis (Mtb) must adapt to a changing environment that is shaped by the developing immune response. This necessity to adapt is evident in the flexibility of many aspects of Mtb metabolism, including a respiratory chain that consists of two distinct terminal cytochrome oxidase complexes. Under the conditions tested thus far, the bc1/aa3 complex appears to play a dominant role, while the alternative bd oxidase is largely redundant. However, presence of two terminal oxidases in this obligate pathogen implies that respiratory requirements might change during infection. We report that the ...


A Cross-Reactive Human Iga Monoclonal Antibody Blocks Sars-Cov-2 Spike-Ace2 Interaction, Ejemel Monir, Qi Li, Shurong Hou, Zachary Schiller, Aaron Wallace, Alla Amcheslavsky, Nese Kurt Yilmaz, Jacqueline R. Toomey, Ryan Schneider, Anudeep S. Ramchetty, Chandrashekar Ganesa, Lisa Cavacini, Mark S. Klempner, Celia A. Schiffer, Yan Wang 2020 University of Massachusetts Medical School

A Cross-Reactive Human Iga Monoclonal Antibody Blocks Sars-Cov-2 Spike-Ace2 Interaction, Ejemel Monir, Qi Li, Shurong Hou, Zachary Schiller, Aaron Wallace, Alla Amcheslavsky, Nese Kurt Yilmaz, Jacqueline R. Toomey, Ryan Schneider, Anudeep S. Ramchetty, Chandrashekar Ganesa, Lisa Cavacini, Mark S. Klempner, Celia A. Schiffer, Yan Wang

COVID-19 Publications by UMMS Authors

COVID-19 caused by SARS-CoV-2 has become a global pandemic requiring the development of interventions for the prevention or treatment to curtail mortality and morbidity. No vaccine to boost mucosal immunity, or as a therapeutic, has yet been developed to SARS-CoV-2. In this study, we discover and characterize a cross-reactive human IgA monoclonal antibody, MAb362. MAb362 binds to both SARS-CoV and SARS-CoV-2 spike proteins and competitively blocks ACE2 receptor binding, by overlapping the ACE2 structural binding epitope. Furthermore, MAb362 IgA neutralizes both pseudotyped SARS-CoV and SARS-CoV-2 in 293 cells expressing ACE2. When converted to secretory IgA, MAb326 also neutralizes authentic SARS-CoV-2 ...


Seroprevalence Of Sars-Cov-2-Specific Igg Antibodies Among Adults Living In Connecticut Between March 1 And June 1, 2020: Post-Infection Prevalence (Pip) Study, Shiwani Mahajan, Lokinendi V. Rao, Harlan M. Krumholz 2020 Yale University

Seroprevalence Of Sars-Cov-2-Specific Igg Antibodies Among Adults Living In Connecticut Between March 1 And June 1, 2020: Post-Infection Prevalence (Pip) Study, Shiwani Mahajan, Lokinendi V. Rao, Harlan M. Krumholz

University of Massachusetts Medical School Faculty Publications

Importance: A seroprevalence study can estimate the percentage of people with SARS-CoV-2 antibodies in the general population. Most existing reports have used a convenience sample, which may bias their estimates.

Objective: To estimate the seroprevalence of antibodies against SARS-CoV-2 based on a random sample of adults living in Connecticut between March 1 and June 1, 2020.

Design: Cross-sectional. Setting: We sought a representative sample of Connecticut residents who completed a survey between June 4 and June 23, 2020 and underwent serology testing for SARS-CoV-2-specific IgG antibodies between June 10 and July 6, 2020.

Participants: 505 respondents, aged ≥18 years, residing ...


The Dhodh Inhibitor Ptc299 Arrests Sars-Cov-2 Replication And Suppresses Induction Of Inflammatory Cytokines, Jeremy Luban, Caterina Strambio De Castilla, Yetao Wang, Allan Jacobson, Stuart Peltz 2020 University of Massachusetts Medical School

The Dhodh Inhibitor Ptc299 Arrests Sars-Cov-2 Replication And Suppresses Induction Of Inflammatory Cytokines, Jeremy Luban, Caterina Strambio De Castilla, Yetao Wang, Allan Jacobson, Stuart Peltz

University of Massachusetts Medical School Faculty Publications

The coronavirus disease 2019 (COVID-19) pandemic has created an urgent need for therapeutics that inhibit the SARS-CoV-2 virus and suppress the fulminant inflammation characteristic of advanced illness. Here, we describe the anti-COVID-19 potential of PTC299, an orally available compound that is a potent inhibitor of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme of the de novo pyrimidine biosynthesis pathway. In tissue culture, PTC299 manifests robust, dose-dependent, and DHODH-dependent inhibition of SARS CoV-2 replication (EC50 range, 2.0 to 31.6 nM) with a selectivity index >3,800. PTC299 also blocked replication of other RNA viruses, including Ebola virus. Consistent with known ...


Performance Of Abbott Architect, Ortho Vitros, And Euroimmun Assays In Detecting Prior Sars-Cov-2 Infection, Shiwani Mahajan, Carrie A. Redlich, Adam V. Wisnewski, Louis E. Fazen, Lokinendi V. Rao, Karthik Kuppusamy, Albert I. Ko, Harlan M. Krumholz 2020 Yale University

Performance Of Abbott Architect, Ortho Vitros, And Euroimmun Assays In Detecting Prior Sars-Cov-2 Infection, Shiwani Mahajan, Carrie A. Redlich, Adam V. Wisnewski, Louis E. Fazen, Lokinendi V. Rao, Karthik Kuppusamy, Albert I. Ko, Harlan M. Krumholz

University of Massachusetts Medical School Faculty Publications

Background: Several serological assays have been developed to detect anti-SARS-CoV-2 IgG antibodies, but evidence about their comparative performance is limited. We sought to assess the sensitivity of four anti-SARS-CoV-2 IgG enzyme-linked immunosorbent assays (ELISA) in individuals with evidence of prior SARS-CoV-2 infection.

Methods: We obtained sera from 36 individuals with PCR-confirmed SARS-CoV-2 infection between March and May 2020. We evaluated samples collected at around 21 days (±14 days) after their initial PCR test using 3 commercially available ELISA assays, two anti-spike (Ortho-Clinical Diagnostics Vitros, and Euroimmun) and one anti-nucleocapsid (Abbott Architect), and a Yale-developed anti-spike ELISA test. We determined the ...


Mycobacterium Tuberculosis Evasion Of Guanylate Binding Protein-Mediated Host Defense In Mice Requires The Esx1 Secretion System, Andrew J. Olive, Clare M. Smith, Christina E. Baer, Jörn Coers, Christopher M. Sassetti 2020 Michigan State University

Mycobacterium Tuberculosis Evasion Of Guanylate Binding Protein-Mediated Host Defense In Mice Requires The Esx1 Secretion System, Andrew J. Olive, Clare M. Smith, Christina E. Baer, Jörn Coers, Christopher M. Sassetti

University of Massachusetts Medical School Faculty Publications

Cell-intrinsic immune mechanisms control intracellular pathogens that infect eukaryotes. The intracellular pathogen Mycobacterium tuberculosis (Mtb) evolved to withstand cell-autonomous immunity to cause persistent infections and disease. A potent inducer of cell-autonomous immunity is the lymphocyte-derived cytokine IFNγ. While the production of IFNγ by T cells is essential to protect against Mtb, it is not capable of fully eradicating Mtb infection. This suggests that Mtb evades a subset of IFNγ-mediated antimicrobial responses, yet what mechanisms Mtb resists remains unclear. The IFNγ-inducible Guanylate binding proteins (GBPs) are key host defense proteins able to control infections with intracellular pathogens. GBPs were previously shown ...


Convalescent Plasma Therapy In Coronavirus Disease 2019 (Covid-19) Patients: A Brief Review, Muhammad Arif Khan, Ikram Ullah 2020 The University of Haripur

Convalescent Plasma Therapy In Coronavirus Disease 2019 (Covid-19) Patients: A Brief Review, Muhammad Arif Khan, Ikram Ullah

The University of Louisville Journal of Respiratory Infections

The recent outbreak of the COVID-19 pandemic has reevaluated effectiveness of the convalescent plasma therapy (CPT). This review was carried out to assess the usefulness of CPT in critically COVID-19 patients, based on the published data to date. To the best of our knowledge, this is the second review of the usefulness of CPT in COVID-19 patients. PubMed, Google Scholar, Medline and EMBASE databases were searched for the relevant reports up to June 21, 2020. All the records of the published data were analyzed according to eligibility criteria protocols. Five different studies on CPT for COVID-19 critically ill patients were ...


Isotype-Specific Outcomes In Fc Gamma Receptor Targeting Of Pspa Using Fusion Proteins As A Vaccination Strategy Against Streptococcus Pneumoniae Infection, Kari Wiedinger 2020 Seton Hall University

Isotype-Specific Outcomes In Fc Gamma Receptor Targeting Of Pspa Using Fusion Proteins As A Vaccination Strategy Against Streptococcus Pneumoniae Infection, Kari Wiedinger

Seton Hall University Dissertations and Theses (ETDs)

Streptococcus pneumoniae (Spn) remains a considerable threat to public health despite the availability of antibiotics and polysaccharide conjugate vaccines. The lack of mucosal immunity in addition to capsular polysaccharide diversity, has proved to be problematic in developing a universal vaccine against Spn. Targeting antigen to Fc receptors is an attractive way to augment both innate and adaptive immunity against mucosal pathogens, by promoting interactions with activating Fcγ receptors (FcγR) that mediate diverse immunomodulatory functions. The effect of targeting FcγR is highly influenced by the IgG subclass, which bares differential affinities for activating and inhibitory FcγR. In the current study we ...


Whims (Washing Hands, Immunity Boost, Masking & Social Distancing), Srinivasan Ragothaman 2020 Srini.Ragothaman@usd.edu

Whims (Washing Hands, Immunity Boost, Masking & Social Distancing), Srinivasan Ragothaman

Creative Work

This is a shot poem about preventing the spread of Covid-19. It pleads general public to wear masks, wash hands, social distance, and boost immunity. It is set to a popular tune in Hindi - Dil Ke Jharoke Mein.


Cd11chi Monocyte-Derived Macrophages Are A Major Cellular Compartment Infected By Mycobacterium Tuberculosis, Jinhee Lee, Shayla Boyce, Jennifer Powers, Christina E. Baer, Christopher M. Sassetti, Samuel M. Behar 2020 University of Massachusetts Medical School

Cd11chi Monocyte-Derived Macrophages Are A Major Cellular Compartment Infected By Mycobacterium Tuberculosis, Jinhee Lee, Shayla Boyce, Jennifer Powers, Christina E. Baer, Christopher M. Sassetti, Samuel M. Behar

Open Access Articles

During tuberculosis, lung myeloid cells have two opposing roles: they are an intracellular niche occupied by Mycobacterium tuberculosis, and they restrict bacterial replication. Lung myeloid cells from mice infected with yellow-fluorescent protein expressing M. tuberculosis were analyzed by flow cytometry and transcriptional profiling to identify the cell types infected and their response to infection. CD14, CD38, and Abca1 were expressed more highly by infected alveolar macrophages and CD11cHi monocyte-derived cells compared to uninfected cells. CD14, CD38, and Abca1 "triple positive" (TP) cells had not only the highest infection rates and bacterial loads, but also a strong interferon-gamma signature and nitric ...


Quercetin And Vitamin C: An Experimental, Synergistic Therapy For The Prevention And Treatment Of Sars-Cov-2 Related Disease (Covid-19), Ruben Manuel Luciano Colunga Biancatelli, Max Berrill, John D. Catravas, Paul Ellis Marik 2020 Old Dominion University

Quercetin And Vitamin C: An Experimental, Synergistic Therapy For The Prevention And Treatment Of Sars-Cov-2 Related Disease (Covid-19), Ruben Manuel Luciano Colunga Biancatelli, Max Berrill, John D. Catravas, Paul Ellis Marik

Bioelectrics Publications

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) represents an emergent global threat which is straining worldwide healthcare capacity. As of May 27th, the disease caused by SARS-CoV-2 (COVID-19) has resulted in more than 340,000 deaths worldwide, with 100,000 deaths in the US alone. It is imperative to study and develop pharmacological treatments suitable for the prevention and treatment of COVID-19. Ascorbic acid is a crucial vitamin necessary for the correct functioning of the immune system. It plays a role in stress response and has shown promising results when administered to the critically ill. Quercetin is a well-known flavonoid whose ...


In Silico Mouse Model Of Infection And Immunity, Daniel Jonas, Michael Kirby, Alan R. Schenkel 2020 Colorado State University

In Silico Mouse Model Of Infection And Immunity, Daniel Jonas, Michael Kirby, Alan R. Schenkel

Biology and Medicine Through Mathematics Conference

No abstract provided.


Maternal Anti-Dengue Igg Fucosylation Predicts Susceptibility To Dengue Disease In Infants, Natalie K. Thulin, R. Camille Brewer, Robert Sherwood, Stylianos Bournazos, Karlie G. Edwards, Nitya S. Ramadoss, Jeffery K. Taubenberger, Matthew Memoli, Andrew J. Gentles, Prasanna Jagannathan, Sheng Zhang, Daniel H. Libraty, Taia T. Wang 2020 Stanford University

Maternal Anti-Dengue Igg Fucosylation Predicts Susceptibility To Dengue Disease In Infants, Natalie K. Thulin, R. Camille Brewer, Robert Sherwood, Stylianos Bournazos, Karlie G. Edwards, Nitya S. Ramadoss, Jeffery K. Taubenberger, Matthew Memoli, Andrew J. Gentles, Prasanna Jagannathan, Sheng Zhang, Daniel H. Libraty, Taia T. Wang

Open Access Articles

Infant mortality from dengue disease is a devastating global health burden that could be minimized with the ability to identify susceptibility for severe disease prior to infection. Although most primary infant dengue infections are asymptomatic, maternally derived anti-dengue immunoglobulin G (IgGs) present during infection can trigger progression to severe disease through antibody-dependent enhancement mechanisms. Importantly, specific characteristics of maternal IgGs that herald progression to severe infant dengue are unknown. Here, we define > /=10% afucosylation of maternal anti-dengue IgGs as a risk factor for susceptibility of infants to symptomatic dengue infections. Mechanistic experiments show that afucosylation of anti-dengue IgGs promotes FcgammaRIIIa ...


Gp41-Targeted Antibodies Restore Infectivity Of A Fusion-Deficient Hiv-1 Envelope Glycoprotein, Vinita R. Joshi, Ruchi M. Newman, Melissa L. Pack, Karen A. Power, James B. Munro, Ken Okawa, Navid Madani, Joseph G. Sodroski, Aaron G. Schmidt, Todd M. Allen 2020 Harvard Medical School

Gp41-Targeted Antibodies Restore Infectivity Of A Fusion-Deficient Hiv-1 Envelope Glycoprotein, Vinita R. Joshi, Ruchi M. Newman, Melissa L. Pack, Karen A. Power, James B. Munro, Ken Okawa, Navid Madani, Joseph G. Sodroski, Aaron G. Schmidt, Todd M. Allen

Open Access Articles

The HIV-1 envelope glycoprotein (Env) mediates viral entry via conformational changes associated with binding the cell surface receptor (CD4) and coreceptor (CCR5/CXCR4), resulting in subsequent fusion of the viral and cellular membranes. While the gp120 Env surface subunit has been extensively studied for its role in viral entry and evasion of the host immune response, the gp41 transmembrane glycoprotein and its role in natural infection are less well characterized. Here, we identified a primary HIV-1 Env variant that consistently supports >300% increased viral infectivity in the presence of autologous or heterologous HIV-positive plasma. However, in the absence of HIV-positive ...


The Influence Of Climate Change On Disease And Public Health, Natalie Petruzelli 2020 St. John Fisher College

The Influence Of Climate Change On Disease And Public Health, Natalie Petruzelli

The Review: A Journal of Undergraduate Student Research

This paper attempts to analyze the growing influence of climate change on the spread and development of diseases, as well as how this continues to affect public health and medical administrations around the world. The prevalence of airborne, waterborne, and vector-borne diseases have been found to be exacerbated as a result of climate change. In addition to this, the paper addresses the reemergence of eliminated diseases and ancient pathogens due to changing temperatures and weather patterns. Finally, the effect of these different conditions on national and international public health organizations and policies is analyzed, including projections on what can be ...


Effect Of Zelnate Administered As A Metaphylactic Upon Initial Processing Of High-Risk, Newly Received Beef Calves On Performance And Morbidity, Brady Martin 2020 University of Arkansas, Fayetteville

Effect Of Zelnate Administered As A Metaphylactic Upon Initial Processing Of High-Risk, Newly Received Beef Calves On Performance And Morbidity, Brady Martin

Animal Science Undergraduate Honors Theses

Bovine Respiratory Disease (BRD) is the most prominent and costly ailment in the stocker cattle industry today, and its prevalence has not been diminished in the last thirty years. Therefore, the objective of this study was to investigate the effects of Zelnate, a DNA immunostimulant, administered upon arrival to calves (n = 261; BW 253 ± 4.0 kg), on morbidity/mortality, performance and producer costs. Crossbred male beef calves were acquired and transported to the University of Arkansas stocker unit for a 42-d backgrounding period. Calves were allocated into treatment groups: 1) Zelnate, DNA immunostimulant administered or 2) Control, in which ...


Characterization Of A Mycoplasma Pneumoniae Cards Toxin Mutant, Nikaash Pasnoori 2020 University of Connecticut

Characterization Of A Mycoplasma Pneumoniae Cards Toxin Mutant, Nikaash Pasnoori

Honors Scholar Theses

Mycoplasma pneumoniae is a high-burden pathogen which causes mild to significant infections of the respiratory system. According to the CDC, an estimated two million cases occur yearly in the United States alone, demonstrating the widespread effect of the pathogen. In addition to being the cause of respiratory infections, M. pneumoniae has also been implicated in exacerbating pre-existing asthma conditions. These morbidities make finding a vaccine candidate a vital part of easing the healthcare burden caused by the pathogen. The current mechanism of infection is unknown, but recent evidence points to the Community Acquired Respiratory Distress Syndrome (CARDS) toxin as being ...


In Vivo Imaging Of The Respiratory Burst Response To Influenza A Virus Infection, James Thomas Seuch 2020 University of Maine

In Vivo Imaging Of The Respiratory Burst Response To Influenza A Virus Infection, James Thomas Seuch

Honors College

The CDC estimated that seasonal influenza A virus (IAV) infections resulted in 490,600 hospitalizations and 34,200 deaths in the US in the 2018-2019 season. The longterm goal of our research is to understand how to improve innate immune responses to IAV. During IAV infection, neutrophils and macrophages initiate a respiratory burst response where reactive oxygen species (ROS) are generated to destroy the pathogen and recruit additional immune cells. While ROS molecules, such as hydrogen peroxide, help clear the virus, the signaling cascade can also lead to excess neutrophil recruitment, hyperinflammation, and tissue damage. Regulatory mechanisms that trigger overactivation ...


Generating Zika Vaccine Candidates Using Nhumirim Virus As A Backbone, Mariam A. Atobiloye 2020 The University of Southern Mississippi

Generating Zika Vaccine Candidates Using Nhumirim Virus As A Backbone, Mariam A. Atobiloye

Honors Theses

Zika virus (ZIKV) is a mosquito-transmitted flavivirus that is causing significant world-wide health concern. There are currently no treatments or vaccines available for this virus, thus, there is an urgent need to develop a safe and effective vaccine to combat ZIKV infection. Nhumirim virus (NHUV) is also a mosquito-transmitted flavivirus, but it is unable to infect humans and other vertebrate animals, making it an ideal candidate to develop chimeric viral vaccines against other disease-causing flaviviruses, such as ZIKV. In this study, we generated chimeric viruses by replacing envelope (E) gene in the genome of NHUV with ZIKV E gene, which ...


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