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Spotlight on Cutting-Edge Original Research on Covid-19

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Spotlight on Cutting-Edge Original Research on Covid-19

We are excited to share some of the cutting-edge Covid-19 related publications and preprint research papers citing the use of our HALO platforms.

  • Identification of immune checkpoints in COVID-19

    Identification of immune checkpoints in COVID-19

    Researchers aiming to block excessive lung inflammation in COVID-19 patients found upregulated immune checkpoint biomarkers in patients with a range of COVID-19 symptoms (from paucisymptomatic to acute respiratory distress syndrome). In addition, Carvelli et al found increased expression of C5a, an inflammatory mediator, in serum and the C5aR1 receptor on myeloid cells in COVID-19 patients, which are known to initiate inflammatory responses by recruiting naeutrophils and monocytes to lungs. An In vitro neutrophil migration assay quantified with the CytoNuclear FL Module of HALO software demonstrated that the clinical stage therapeutic monoclonal antibody, avdoralimab, effectively inhibited C5a-induced neutrophil migration. The authors propose use of avdoralimab to limit excessive lung inflammation associated with acute respiratory distress in COVID-19 patients.Read More »
  • Baricitinib treatment resolves lower airway inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques

    Baricitinib treatment resolves lower airway inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques

    Hoang, T.N., Pino, M., Boddapati, A.K. et al.. Baricitinib treatment resolves lower airway inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques. This article is a preprint and has not been certified by peer review, doi: https://doi.org/10.1101/2020.09.16.300277 Effective therapeutics aimed at mitigating COVID-19 symptoms are urgently needed. SARS-CoV-2 induced hypercytokinemia and systemic inflammation are associated with disease severity. Baricitinib, a clinically approved JAK1/2 inhibitor with potent anti-inflammatory properties is currently being investigated in COVID-19 human clinical trials. Recent reports suggest that...Read More »
  • ARDS and Cytokine Storm in SARS-CoV-2 Infected Caribbean Vervets

    ARDS and Cytokine Storm in SARS-CoV-2 Infected Caribbean Vervets

    Blair, R.V., Vaccari, M., Doyle-Meyers, L.A.. et al. ARDS and Cytokine Storm in SARS-CoV-2 Infected Caribbean Vervets. This article is a preprint and has not been certified by peer review. doi: https://doi.org/10.1101/2020.06.18.157933 SARS-CoV-2 induces a wide range of disease severity ranging from asymptomatic infection, to a life-threating illness, particularly in the elderly and persons with comorbid conditions. Up to now, SARS-CoV-2 has infected more than five million and led to more than 300,000 deaths worldwide. Among those persons with serious...Read More »
  • Acute Respiratory Distress and Cytokine Storm in Aged, SARS-CoV-2 Infected African Green Monkeys, but not in Rhesus Macaques

    Acute Respiratory Distress and Cytokine Storm in Aged, SARS-CoV-2 Infected African Green Monkeys, but not in Rhesus Macaques

    Blair, R.V., Vaccari, M., Doyle-Meyers, L.A.. et al. Acute Respiratory Distress and Cytokine Storm in Aged, SARS-CoV-2 Infected African Green Monkeys, but not in Rhesus Macaques. This article is a preprint and has not been certified by peer review.  doi: https://doi.org/10.1101/2020.06.18.157933. SARS-CoV-2 induces a wide range of disease severity ranging from asymptomatic infection, to a life-threating illness, particularly in the elderly and persons with comorbid conditions. Among those persons with serious COVID-19 disease, acute respiratory distress syndrome (ARDS) is a common and often fatal presentation. Animal models of SARS-CoV-2 infection that manifest severe disease are needed to investigate the pathogenesis of COVID-19 induced ARDS and evaluate therapeutic strategies.Read More »
  • Neuropathology and Virus in Brain of SARS-CoV-2 Infected Non-Human Primates

    Neuropathology and Virus in Brain of SARS-CoV-2 Infected Non-Human Primates

    Rutkai, I., Mayer, M.G., Hellmers, L.M., et al. Neuropathology and Virus in Brain of SARS-CoV-2 Infected Non-Human Primates. This article is a preprint and has not been certified by peer review. DOI: 10.21203/rs.3.rs-59871/v1 Neurological manifestations are a significant complication of coronavirus infection disease-19 (COVID-19). Understanding how COVID-19 contributes to neurological disease is needed for appropriate treatment of infected patients, as well as in initiating relevant follow-up care after recovery. Investigation of autopsied brain tissue has been key to advancing our...Read More »
  • Lung Expression of Human ACE2 Sensitizes the Mouse to SARS-CoV-2 Infection

    Lung Expression of Human ACE2 Sensitizes the Mouse to SARS-CoV-2 Infection

    Han, K., Blair, R.V., Iwanaga ,N., et al. Lung Expression of Human ACE2 Sensitizes the Mouse to SARS-CoV-2 Infection. Am J Respir Cell Mol Biol. 2020 Sep 29. Preclinical mouse models that recapitulate some characteristics of COVID-19 will facilitate focused study of pathogenesis and virus-host responses. Human angiotensin converting enzyme (hACE2) serves as an entry receptor for SARS-CoV-2 to infect people via binding to spike proteins. Herein we report development and characterization of a rapidly deployable COVID-19 mouse model. C57BL/6J...Read More »
  • Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters

    Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters

    Lisa H Tostanoski, et al, Nature Medicine, 2020 In this study led by researchers at Harvard Medical School, they report the first demonstration of prevention of severe clinical disease in a hamster model of SARS-CoV-2 that were provided with a single immunization of the adenovirus serotype 26 (Ad26) vaccine. The Ad26 vaccine utilizes a stabilized spike protein of the SARS-CoV-2 and in the United States this vaccine is commonly known as the Johnson and Johnson vaccine. This study, published in print in November 2020 contributed to the scientific body of evidence in animal models that enabled clinical vaccine trials that in turn led to emergency use approvals in the United States, Canada, and other countries. Researchers leveraged the Multiplex IHC module of HALO for evaluation of the percentage of SAR-N protein positive cells and for Iba-1 quantification. The Area Quantification IHC module was used to determine the percentage of SARS-CoV-2 sense or anti-sense probe or Mx1 protein as a function of area. The Cytonuclear IHC module and Area Quantification IHC modules were used in detection of MPO+ or CD3+ cells expressed as a proportion of total alveolar tissue.Read More »
  • Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates

    Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates

    Fahlberg, M.D., Blair, R.V., Doyle-Meyers, L.A. et al. Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates.  This article is a preprint and has not been certified by peer review. doi: https://doi.org/10.1101/2020.07.21.213777.  We investigated the immune events following SARS-COV-2 infection, from the acute inflammatory state up to four weeks post infection, in non-human primates (NHP) with heterogeneous pulmonary pathology. The acute phase was characterized by a rapid migration of CD16+ monocytes from the blood and concomitant...Read More »
  • ACE2 and SARS-CoV-2 Expression in the Normal and COVID-19 Pancreas

    ACE2 and SARS-CoV-2 Expression in the Normal and COVID-19 Pancreas

    Kusmartseva, I., Wu, W., Syed, F. et al. ACE2 and SARS-CoV-2 Expression in the Normal and COVID-19 Pancreas. This article is a preprint and has not been certified by peer review.  doi: https://doi.org/10.1101/2020.08.31.270736 Diabetes is associated with increased mortality from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Given literature suggesting a potential association between SARS-CoV-2 infection and diabetes induction, we examined pancreatic expression of the key molecule for SARS-CoV-2 infection of cells, angiotensin-converting enzyme-2 (ACE2). Specifically, we analyzed five public scRNAseq...Read More »
  • Two distinct immunopathological profiles in autopsy lungs of COVID-19

    Two distinct immunopathological profiles in autopsy lungs of COVID-19

    Ronny Nienhold, et al, Nature Communications, 2020An international consortium of researchers characterized lung tissue from patients with COVID-19 using transcriptomic, histologic, and cellular analyses. Nienhold and colleagues report two phenotypes associated with lethal COVID-19 disease. One showed high levels of interferon stimulated genes in the lungs as well as limited lung damage and high levels of cytokines and viral loads. The second phenotype included severe lung damage with low levels of interferon stimulated genes, low viral loads, and high levels of CD8+ T cells and macrophages. As patients with the first phenotype die sooner, this highlights the need for biomarkers to classify COVID-19 patients and potentially guide treatment. HALO AI was trained using annotations from a pathologist to identify lung tissue and the resulting output was confirmed by pathology review. HALO was also used for quantification of immunohistochemistry analysis of CD3, CD4, CD8, CD20, CD68, CD123, CD163, and PD1.Read More »
  • Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 infection in the lung epithelium

    Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 infection in the lung epithelium

    Bryce A. Schuler, A. Christian Habermann, Erin J. Plosa, Chase J. Taylor, Christopher Jetter, Meghan E. Kapp, John T. Benjamin, Peter Gulleman, David S. Nichols, Lior Z. Braunstein, Alice Hackett, View ORCID ProfileMichael Koval, Susan H. Guttentag, Timothy S. Blackwell, Vanderbilt COVID-19 Consortium Cohort, Steven A. Webber, Nicholas E. Banovich, View ORCID ProfileJonathan A. Kropski, Jennifer M. S. Sucre, HCA Lung Biological Network bioRxiv | Posted August 03, 2020 | This article is a preprint and has not been certified...Read More »