Immunology of Infectious Disease News Volume 8.15 | Apr 22 2020

TOP STORY

Endothelial Cell Infection and Endotheliitis in COVID-19

Whether vascular derangements in COVID-19 are due to endothelial cell involvement by the virus is currently unknown. Researchers demonstrated endothelial cell involvement across vascular beds of different organs in a series of patients with COVID-19. [Lancet] Full Article

(Ranked by impact factor of the journal)

SARS-CoV-2

Comparative Pathogenesis of COVID-19, MERS, and SARS in a Non-Human Primate Model

To compare SARS-CoV-2 pathogenesis with that of previously emerging coronaviruses, the authors inoculated cynomolgus macaques with SARS-CoV-2 or MERS-CoV and compared the pathology and virology with historical reports of SARS-CoV infections. [Science] Full Article

Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure

Investigators studied immune responses of 54 COVID-19 patients, 28 of whom had severe respiratory failure (SRF). All patients with SRF displayed either macrophage activation syndrome or very low human leukocyte antigen D related expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and NK cells. [Cell Host Microbe] Full Article | Graphical Abstract

Human Monoclonal Antibodies Block the Binding of SARS-CoV-2 Spike Protein to Angiotensin Converting Enzyme 2 Receptor

Scientists sought to identify and clone blocking monoclonal antibodies from the memory B cell repertoire of recently recovered COVID-19 patients to prevent the entry of COVID-19 virus to the host cells. [Cell Mol Immunol] Full Article

Human Leukocyte Antigen Susceptibility Map for SARS-CoV-2

Investigators executed a comprehensive in silico analysis of viral peptide-MHC class I binding affinity across 145 HLA -A, -B, and -C genotypes for all SARS-CoV-2 peptides. They explored the potential for cross-protective immunity conferred by prior exposure to four common human coronaviruses. [J Virol] Abstract | Full Article

Crystal Structure of Nsp15 Endoribonuclease NendoU from SARS-CoV-2

Researchers applied high-throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS-CoV-2 proteins and structures. They report two high-resolution crystal structures of endoribonuclease Nsp15/NendoU. [Protein Sci] Abstract | Full Article

Antibody Detection and Dynamic Characteristics in Patients with COVID-19

The antibodies against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay based on the recombinant nucleocapsid protein of SARS-CoV-2 in patients with confirmed or suspected COVID-19 at 3-40 days after symptom onset. The gold standard for COVID-19 diagnosis was nucleic acid testing for SARS-CoV-2 by RT-PCR. [Int Immunopharmacol] Full Article

Central Nervous System Involvement by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)

The authors report the presence of virus in neural and capillary endothelial cells in frontal lobe tissue obtained at postmortem examination from a patient infected with SARS-CoV-2. [J Med Virol] Abstract

MORE IMMUNOLOGY OF INFECTIOUS DISEASE

Caspase-6 Is a Key Regulator of Innate Immunity, Inflammasome Activation, and Host Defense

Researchers showed that caspase-6 mediated innate immunity and inflammasome activation. They demonstrated that caspase-6 promoted the activation of programmed cell death pathways including pyroptosis, apoptosis, and necroptosis and played an essential role in host defense against influenza A virus infection. [Cell] Abstract | Graphical Abstract

A Minor Population of Macrophage-Tropic HIV-1 Variants Is Identified in Recrudescing Viremia following Analytic Treatment Interruption

Macrophage-tropic (M-tropic) viruses could be enriched from post-analytic treatment interruption plasma using macrophage-specific but not CD4⁺ T cell-specific antibodies, suggesting that M-tropic viruses had a macrophage origin. [Proc Natl Acad Sci USA] Abstract

Cellular Importin-α3 Expression Dynamics in the Lung Regulate Antiviral Response Pathways against Influenza A Virus Infection

High-level TNF-α-inducing highly pathogenic avian influenza A viruses (HPAIVs) isolated from fatal human cases harboring human-type polymerase signatures significantly downregulated importin-α3 mRNA expression in primary lung cells. Importin-α3 depletion was restored upon back-mutating the HPAIV polymerase into an avian-type signature that could no longer induce high TNF-α levels. [Cell Rep] Full Article | Graphical Abstract

Staphylococcus aureus Alpha-Toxin Inhibits CD8⁺ T Cell-Mediated Killing of Cancer Cells in Cutaneous T-Cell Lymphoma

Scientists showed that CD8⁺ T cells from both healthy donors and Sézary syndrome patients were highly susceptible to cell death induced by Staphylococcal alpha-toxin, whereas malignant T cells were not. [Oncoimmunology] Full Article

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Seasonal and Pandemic Influenza: 100 Years of Progress, Still Much to Learn

The authors highlight the importance of the mucosa in defense against infection and in understanding the pathogenesis of disease. Although vaccines have been available for many decades, they remain suboptimal in needing constant redesign and in only providing short-term protection. [Mucosal Immunol] Full Article

SARS-Cov-2 Infection: Response of Human Immune System and Possible Implications for the Rapid Test and Treatment

Investigators describe the importance of sensitive and specific rapid test for SARS-CoV-2. They also provide an overview of pharmacological treatments aimed to reduce inflammatory processes underlying the infection and the need for the discovery of a new vaccine against SARS-CoV-2. [Int Immunopharmacol] Full Article

Visit our reviews page to see a complete list of reviews in the immunology of infectious disease research field.

Drug Repurposing for SARS-CoV-2 Infection Using Human Organoid Culture Technology

This project will test thousands of FDA-approved drugs and other clinical-stage compounds alone and in combination with each other to see how effective they are in combating SARS-CoV-2 infections. The most promising potential therapies will be evaluated on a state-of-the-art human airway cell platform developed with collaborator and local biotech leader STEMCELL Technologies, and tested for their ability to inhibit all stages of the virus lifecycle. [STEMCELL Technologies, Inc.] Press Release

Karyopharm Announces Dosing of First Patient in Randomized Study Evaluating Low Dose Selinexor in Patients with Severe COVID-19

Karyopharm Therapeutics, Inc. announced dosing of the first patient in a randomized Phase II clinical study evaluating low dose oral selinexor in hospitalized patients with severe COVID-19. This global study is expected to enroll approximately 230 patients at clinical sites in the US, Europe, and Israel. [Karyopharm Therapeutics Inc.] Press Release

INmune Bio, Inc. Announces Initiation of Clinical Program Targeting Soluble TNF to Determine if the Company’s TNF Inhibitor (DN-TNF) Platform May Prevent Complications of Cytokine Storm Caused by COVID-19

INmune Bio, Inc. announced the initiation of a therapeutic program to treat patients with pulmonary complications from COVID-19 infection with its dominant-negative TNF inhibitor platform. [INmune Bio, Inc.] Press Release

Moderna Announces Award from US Government Agency BARDA for up to $483 Million to Accelerate Development of mRNA Vaccine (mRNA-1273) against Novel Coronavirus

Moderna, Inc. announced an agreement for a commitment of up to $483 million from the Biomedical Advanced Research and Development Authority (BARDA), a division of the Office of the Assistant Secretary for Preparedness and Response within the US Department of Health and Human Services, to accelerate development of the company’s mRNA vaccine candidate against the novel coronavirus. [Moderna, Inc.] Press Release

Hundreds of People Volunteer to Be Infected with Coronavirus

Momentum is building to speed the development of coronavirus vaccines by intentionally infecting healthy, young volunteers with the virus. A grass-roots effort has attracted nearly 1,500 potential volunteers for the controversial approach, known as a human-challenge trial. [Nature News] Editorial

The Researchers Taking a Gamble with Antibody Tests for Coronavirus

Researchers have been using antibody tests to try to reveal the true spread of the coronavirus in communities and cities. But these latest efforts are more controversial because they focus on an individual’s immune status. [Nature News] Editorial

Director of US Agency Key to Vaccine Development Leaves Role Suddenly amid Coronavirus Pandemic

Rick Bright, one of the nation’s leading vaccine development experts and the director of the Biomedical Advanced Research and Development Authority, is no longer leading the organization, officials told STAT. [STAT News] Editorial

Did Japan Miss Its Chance to Keep the Coronavirus in Check?

Over the past several weeks, Hokkaido University epidemiologist Hiroshi Nishiura has given innumerable TV and newspaper interviews urging the public to reduce social contact by 80% in order to reverse the suddenly explosive growth of Japan’s COVID-19 epidemic. “Cooperate to reduce contacts immediately in a drastic manner,” Nishiura keeps saying. [ScienceInsider] Editorial

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NEW Director – Malaria Research (Johns Hopkins University)

Chair – Department of Microbiology and Immunology (Western University)

Postdoctoral Fellow – Mucosal Biology (University of Gothenburg)

Group Leader – Anti-Microbial Resistance (Helmholtz Centre for Infection Research)

Professorship – Epidemiology in Occupational Medicine (Jena University Hospital)

Research Fellow – COVID-19 Virology (Queen’s University Belfast)

Research Fellow – Vaccine Research (Mayo Clinic)

Postdoctoral Researcher – Respiratory Viruses (Flanders Institute for Biotechnology)

Postdoctoral Research Fellowship – Molecular Infection Biology (Umeå University)

Postdoctoral Fellow/Research Scientist – Hepatitis Research (Nationwide Children’s Hospital)

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