Virus Induced Lymphocytes (VIL) as a Novel Viral Antigen-Specific T Cell Therapy for COVID-19 and Potential Future Pandemics

Using a novel SARS-Cov-2-specific artificial antigen presenting cell, coupled with a rapid expansion protocol as practiced in tumor infiltrating lymphocytes therapy, researchers generated an immune catalytic quantity of VIL.
[Scientific Reports]
Sivapalan, R., Liu, J., Chakraborty, K., Arthofer, E., Choudhry, M., Barie, P. S., Barouch, D. H., & Henley, T. (2021). Virus Induced Lymphocytes (VIL) as a novel viral antigen-specific T cell therapy for COVID-19 and potential future pandemics. Scientific Reports, 11(1), 15295. https://doi.org/10.1038/s41598-021-94654-y Cite
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Impaired Local Intrinsic Immunity to SARS-CoV-2 Infection in Severe COVID-19

Researchers performed scRNA-seq on nasopharyngeal swabs from 58 healthy and COVID-19 participants. During COVID-19, we observe expansion of secretory, loss of ciliated, and epithelial cell repopulation via deuterosomal expansion.
[Cell]
Ziegler, C. G. K., Miao, V. N., Owings, A. H., Navia, A. W., Tang, Y., Bromley, J. D., Lotfy, P., Sloan, M., Laird, H., Williams, H. B., George, M., Drake, R. S., Christian, T., Parker, A., Sindel, C. B., Burger, M. W., Pride, Y., Hasan, M., Abraham, G. E., … Ordovas-Montanes, J. (2021). Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19. Cell. https://doi.org/10.1016/j.cell.2021.07.023 Cite
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Complement Dysregulation Is Associated with Severe COVID-19 Illness

Researchers demonstrated that serum from 58 COVID-19 patients could induce complement-mediated cell death in a functional assay and increase membrane attack complex deposition on the cell surface.
[Haematologica]
Yu, J., Gerber, G. F., Chen, H., Yuan, X., Chaturvedi, S., Braunstein, E. M., & Brodsky, R. A. (2020). Complement dysregulation is associated with severe COVID-19 illness. Haematologica. https://doi.org/10.3324/haematol.2021.279155 Cite
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SARS-CoV-2 Nucleocapsid Suppresses Host Pyroptosis by Blocking Gasdermin D Cleavage

Investigators showed that the nucleocapsid of SARS-CoV-2 inhibited host pyroptosis by blocking Gasdermin D cleavage. SARS-CoV-2-infected monocytes showed enhanced cellular interleukin 1b (IL-1b) expression, but reduced IL-1b secretion.
[EMBO Journal]
SARS-CoV-2 nucleocapsid suppresses host pyroptosis by blocking Gasdermin D cleavage. (2021). The EMBO Journal, n/a(n/a), e108249. https://doi.org/10.15252/embj.2021108249 Cite
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SARS-CoV-2 Activates Lung Epithelial Cell Proinflammatory Signaling and Leads to Immune Dysregulation in COVID-19 Patients

The authors aimed to decipher SARS-CoV-2 infected cell types, the consequent host immune response and their interplay in lung of COVID-19 patients.
[EBiomedicine]
Chen, H., Liu, W., Wang, Y., Liu, D., Zhao, L., & Yu, J. (2021). SARS-CoV-2 activates lung epithelial cell proinflammatory signaling and leads to immune dysregulation in COVID-19 patients. EBioMedicine, 70. https://doi.org/10.1016/j.ebiom.2021.103500 Cite
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Inhibitors of VPS34 and Fatty-Acid Metabolism Suppress SARS-CoV-2 Replication

Researchers tested small molecule inhibitors that target the PI3 kinase VPS34 or fatty acid metabolism for anti-SARS-CoV-2 activity. Their studies determined that compounds targeting VPS34 were potent SARS-CoV-2 inhibitors.
[Cell Reports]
Williams, C. G., Jureka, A. S., Silvas, J. A., Nicolini, A. M., Chvatal, S. A., Carlson-Stevermer, J., Oki, J., Holden, K., & Basler, C. F. (2021). Inhibitors of VPS34 and fatty-acid metabolism suppress SARS-CoV-2 replication. Cell Reports, 109479. https://doi.org/10.1016/j.celrep.2021.109479 Cite
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Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques

To investigate the specific role of T cells in recovery from SARS-CoV-2 infections, researchers studied rhesus macaques that were depleted of either CD4+, CD8+, or both T cell subsets prior to infection.
[mBio]
Hasenkrug, K. J., Feldmann, F., Myers, L., Santiago, M. L., Guo, K., Barrett, B. S., Mickens, K. L., Carmody, A., Okumura, A., Rao, D., Collins, M. M., Messer, R. J., Lovaglio, J., Shaia, C., Rosenke, R., van Doremalen, N., Clancy, C., Saturday, G., Hanley, P., … Feldmann, H. (n.d.). Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques. MBio, 0(0), e01503-21. https://doi.org/10.1128/mBio.01503-21 Cite
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Neutralizing Activity of Sputnik V Vaccine Sera against SARS-CoV-2 Variants

Researchers characterized the neutralizing activity of post-Sputnik V vaccination sera against the ensemble of S mutations present in alpha and beta variants of concern.
[Nature Communications]
Ikegame, S., Siddiquey, M. N. A., Hung, C.-T., Haas, G., Brambilla, L., Oguntuyo, K. Y., Kowdle, S., Chiu, H.-P., Stevens, C. S., Vilardo, A. E., Edelstein, A., Perandones, C., Kamil, J. P., & Lee, B. (2021). Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants. Nature Communications, 12(1), 4598. https://doi.org/10.1038/s41467-021-24909-9 Cite
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Differentiation of Exhausted CD8+ T Cells after Termination of Chronic Antigen Stimulation Stops Short of Achieving Functional T Cell Memory

The authors confirmed pervasive phenotypic, functional and transcriptional differences between memory and exhausted antigen-specific CD8+ T cells in human hepatitis C virus infection before and after treatment.
[Nature Immunology]
Tonnerre, P., Wolski, D., Subudhi, S., Aljabban, J., Hoogeveen, R. C., Damasio, M., Drescher, H. K., Bartsch, L. M., Tully, D. C., Sen, D. R., Bean, D. J., Brown, J., Torres-Cornejo, A., Robidoux, M., Kvistad, D., Alatrakchi, N., Cui, A., Lieb, D., Cheney, J. A., … Lauer, G. M. (2021). Differentiation of exhausted CD8+ T cells after termination of chronic antigen stimulation stops short of achieving functional T cell memory. Nature Immunology, 22(8), 1030–1041. https://doi.org/10.1038/s41590-021-00982-6 Cite
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Single-Cell RNA Sequencing Reveals Ex Vivo Signatures of SARS-CoV-2-Reactive T Cells through ‘Reverse Phenotyping’

Investigators used single-cell RNA sequencing to identify and profile SARS-CoV-2-reactive T cells from COVID-19 patients.
[Nature Communications]
Fischer, D. S., Ansari, M., Wagner, K. I., Jarosch, S., Huang, Y., Mayr, C. H., Strunz, M., Lang, N. J., D’Ippolito, E., Hammel, M., Mateyka, L., Weber, S., Wolff, L. S., Witter, K., Fernandez, I. E., Leuschner, G., Milger, K., Frankenberger, M., Nowak, L., … Schober, K. (2021). Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through ‘reverse phenotyping.’ Nature Communications, 12(1), 4515. https://doi.org/10.1038/s41467-021-24730-4 Cite
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Immunogenicity and Reactogenicity of Heterologous ChAdOx1 nCoV-19/mRNA Vaccination

Spike-specific CD8 T cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens.
[Nature Medicine]
Schmidt, T., Klemis, V., Schub, D., Mihm, J., Hielscher, F., Marx, S., Abu-Omar, A., Ziegler, L., Guckelmus, C., Urschel, R., Schneitler, S., Becker, S. L., Gärtner, B. C., Sester, U., & Sester, M. (2021). Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination. Nature Medicine, 1–6. https://doi.org/10.1038/s41591-021-01464-w Cite
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