AzurRx BioPharma Initiates Phase II Clinical Trial of Niclosamide for the Treatment of COVID-19 Gastrointestinal Infections

AzurRx BioPharma, Inc. announced that it has initiated its Phase II RESERVOIR clinical trial of a proprietary oral formulation of micronized niclosamide for the treatment of COVID-19 related gastrointestinal infections.
[AzurRx BioPharma, Inc.]
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Mesenchymal Stem Cells for the Compassionate Treatment of Severe Acute Respiratory Distress Syndrome Due to COVID 19

Scientists evaluated the safety and describe the clinical changes after IV administration of allogeneic human umbilical cord MSCs, in patients with bilateral pneumonia caused by COVID-19, complicated with severe acute respiratory distress syndrome, as compassionate treatment.
[Aging and Disease]
Iglesias Martin, B. P., & Iglesias Martin, B. P. (2021). Mesenchymal Stem Cells for the Compassionate Treatment of Severe Acute Respiratory Distress Syndrome Due to COVID 19. Aging and Disease, 12(2), 360–370. https://doi.org/10.14336/AD.2020.1218 Cite
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BeiGene Provides Update on Phase II Clinical Trial of Zanubrutinib in Patients with COVID-19-Related Pulmonary Distress

-BeiGene, Ltd. announced that the Phase II trial evaluating BRUKINSA® in patients hospitalized with respiratory symptoms of COVID-19, requiring supplemental oxygen without mechanical ventilation, did not meet the co-primary efficacy endpoints of respiratory failure-free survival or reduction in days on oxygen as compared to placebo.
[BeiGene, Ltd. (BusinessWire, Inc.)]
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SARS-CoV-2 Drives JAK1/2-Dependent Local Complement Hyperactivation

Scientists unexpectedly found that the complement system was one of the intracellular pathways most highly induced by SARS-CoV-2 infection in lung epithelial cells.
[Science Immunology]
Yan, B., Freiwald, T., Chauss, D., Wang, L., West, E., Mirabelli, C., Zhang, C. J., Nichols, E.-M., Malik, N., Gregory, R., Bantscheff, M., Ghidelli-Disse, S., Kolev, M., Frum, T., Spence, J. R., Sexton, J. Z., Alysandratos, K. D., Kotton, D. N., Pittaluga, S., … Kazemian, M. (2021). SARS-CoV-2 drives JAK1/2-dependent local complement hyperactivation. Science Immunology, 6(58). https://doi.org/10.1126/sciimmunol.abg0833 Cite
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Durability of Immunity to SARS-CoV-2 and Other Respiratory Viruses

The authors summarize what is now known about adaptive immunity to SARS-CoV-2 and draw comparisons with immunity to other respiratory viruses, focusing on the longevity of protective responses.
[Trends in Microbiology]
Siggins, M. K., Thwaites, R. S., & Openshaw, P. J. M. (2021). Durability of immunity to SARS-CoV-2 and other respiratory viruses. Trends in Microbiology, 0(0). https://doi.org/10.1016/j.tim.2021.03.016 Cite
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SARS-CoV-2 Mutations Acquired in Mink Reduce Antibody-Mediated Neutralization

Scientists report that mutations frequently found in the S proteins of SARS-CoV-2 from mink were mostly compatible with efficient entry into human cells and its inhibition by soluble ACE2.
[Cell Reports]
Hoffmann, M., Zhang, L., Krüger, N., Graichen, L., Kleine-Weber, H., Hofmann-Winkler, H., Kempf, A., Nessler, S., Riggert, J., Winkler, M. S., Schulz, S., Jäck, H.-M., & Pöhlmann, S. (2021). SARS-CoV-2 mutations acquired in mink reduce antibody-mediated neutralization. Cell Reports, 0(0). https://doi.org/10.1016/j.celrep.2021.109017 Cite
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The Neutralizing Antibody, LY-CoV555, Protects against SARS-CoV-2 Infection in Non-human Primates

Researchers report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555, a potent anti-spike neutralizing antibody from a hospitalized, convalescent patient with COVID-19.
[Science Translational Medicine]
Jones, B. E., Brown-Augsburger, P. L., Corbett, K. S., Westendorf, K., Davies, J., Cujec, T. P., Wiethoff, C. M., Blackbourne, J. L., Heinz, B. A., Foster, D., Higgs, R. E., Balasubramaniam, D., Wang, L., Zhang, Y., Yang, E. S., Bidshahri, R., Kraft, L., Hwang, Y., Žentelis, S., … Falconer, E. (2021). The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in non-human primates. Science Translational Medicine. https://doi.org/10.1126/scitranslmed.abf1906 Cite
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T Cell Assays Differentiate Clinical and Subclinical SARS-CoV-2 Infections from Cross-Reactive Antiviral Responses

Scientists showed a range of T cell assays that differentially captured immune function to characterise SARS-CoV-2 responses.
[Nature Communications]
Ogbe, A., Kronsteiner, B., Skelly, D. T., Pace, M., Brown, A., Adland, E., Adair, K., Akhter, H. D., Ali, M., Ali, S.-E., Angyal, A., Ansari, M. A., Arancibia-Cárcamo, C. V., Brown, H., Chinnakannan, S., Conlon, C., de Lara, C., de Silva, T., Dold, C., … Dunachie, S. (2021). T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses. Nature Communications, 12(1), 2055. https://doi.org/10.1038/s41467-021-21856-3 Cite
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Endothelial Dysfunction and Immunothrombosis as Key Pathogenic Mechanisms in COVID-19

Scientists propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels.
[Nature Reviews Immunology]
Bonaventura, A., Vecchié, A., Dagna, L., Martinod, K., Dixon, D. L., Van Tassell, B. W., Dentali, F., Montecucco, F., Massberg, S., Levi, M., & Abbate, A. (2021). Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19. Nature Reviews Immunology, 1–11. https://doi.org/10.1038/s41577-021-00536-9 Cite
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Hypoxic and Pharmacological Activation of HIFs Inhibits SARS-CoV-2 Infection of Lung Epithelial Cells

Scientists demonstrated that hypoxia and the hypoxia inducible factor (HIF) prolyl hydroxylase inhibitor Roxadustat reduced angiotensin-converting enzyme expression and inhibited SARS-CoV-2 entry and replication in lung epithelial cells via a HIF-1α dependent pathway.
[Cell Reports]
Wing, P. A., Keeley, T. P., Zhuang, X., Lee, J. Y., Prange-Barczynska, M., Tsukuda, S., Morgan, S. B., Harding, A. C., Argles, I. L. A., Kurlekar, S., Noerenberg, M., Thompson, C. P., Huang, K.-Y. A., Balfe, P., Watashi, K., Castello, A., Hinks, T. S., James, W., Ratcliffe, P. J., … McKeating, J. A. (2021). Hypoxic and pharmacological activation of HIFs inhibits SARS-CoV-2 infection of lung epithelial cells. Cell Reports, 0(0). https://doi.org/10.1016/j.celrep.2021.109020 Cite
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Foresee Pharmaceuticals Announces Dosing of First Patient in Phase II/III Clinical Trial of FP-025 for Treatment of COVID-19 Associated ARDS

Foresee Pharmaceuticals Co., Ltd. announced the initiation of patient dosing in the Phase II/III clinical trial of FP-025, its highly selective oral MMP-12 inhibitor, in adult patients with severe to critical COVID-19 with associated Acute Respiratory Distress Syndrome.
[Foresee Pharmaceuticals Co., Ltd.]
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