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Thompson EA, Cascino K, Ordonez AA, et al. Metabolic programs define dysfunctional immune responses in severe COVID-19 patients. medRxiv. 2020;doi: 10.1101/2020.09.10.20186064.
Thompson, E. A., Cascino, K., Ordonez, A. A., Zhou, W., Vaghasia, A., Hamacher-Brady, A., Brady, N. R., Sun, I. H., Wang, R., Rosenberg, A. Z., Delannoy, M., Rothman, R., Fenstermacher, K., Sauer, L., Shaw-Saliba, K., Bloch, E. M., Redd, A. D., Tobian, A. A., Horton, M., Smith, K., Pekosz, A., D'Alessio, F. R., Yegnasubramanian, S., Ji, H., Cox, A. L., & Powell, J. D. (2020). Metabolic programs define dysfunctional immune responses in severe COVID-19 patients. medRxiv : the preprint server for health sciences, . https://doi.org/10.1101/2020.09.10.20186064
Thompson, Elizabeth A, et al. "Metabolic programs define dysfunctional immune responses in severe COVID-19 patients." medRxiv : the preprint server for health sciences vol. (2020). doi: https://doi.org/10.1101/2020.09.10.20186064
Thompson EA, Cascino K, Ordonez AA, Zhou W, Vaghasia A, Hamacher-Brady A, Brady NR, Sun IH, Wang R, Rosenberg AZ, Delannoy M, Rothman R, Fenstermacher K, Sauer L, Shaw-Saliba K, Bloch EM, Redd AD, Tobian AA, Horton M, Smith K, Pekosz A, D'Alessio FR, Yegnasubramanian S, Ji H, Cox AL, Powell JD. Metabolic programs define dysfunctional immune responses in severe COVID-19 patients. medRxiv. 2020 Oct 05; doi: 10.1101/2020.09.10.20186064. PMID: 32935120; PMCID: PMC7491535.
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medRxiv. 2020 Oct 05; doi: 10.1101/2020.09.10.20186064.

Metabolic programs define dysfunctional immune responses in severe COVID-19 patients.

medRxiv : the preprint server for health sciences

Elizabeth A Thompson, Katherine Cascino, Alvaro A Ordonez, Weiqiang Zhou, Ajay Vaghasia, Anne Hamacher-Brady, Nathan R Brady, Im-Hong Sun, Rulin Wang, Avi Z Rosenberg, Michael Delannoy, Richard Rothman, Katherine Fenstermacher, Lauren Sauer, Kathyrn Shaw-Saliba, Evan M Bloch, Andrew D Redd, Aaron Ar Tobian, Maureen Horton, Kellie Smith, Andrew Pekosz, Franco R D'Alessio, Srinivasan Yegnasubramanian, Hongkai Ji, Andrea L Cox, Jonathan D Powell

Affiliations

  1. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  2. Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  3. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  4. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  5. Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA.
  6. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA.
  7. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  8. Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  9. Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  10. Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Baltimore, MD 21205, USA.

PMID: 32935120 PMCID: PMC7491535 DOI: 10.1101/2020.09.10.20186064

Abstract

It remains unclear why some patients infected with SARS-CoV-2 readily resolve infection while others develop severe disease. To address this question, we employed a novel assay to interrogate immune-metabolic programs of T cells and myeloid cells in severe and recovered COVID-19 patients. Using this approach, we identified a unique population of T cells expressing high H3K27me3 and the mitochondrial membrane protein voltage-dependent anion channel (VDAC), which were expanded in acutely ill COVID-19 patients and distinct from T cells found in patients infected with hepatitis c or influenza and in recovered COVID-19. Increased VDAC was associated with gene programs linked to mitochondrial dysfunction and apoptosis. High-resolution fluorescence and electron microscopy imaging of the cells revealed dysmorphic mitochondria and release of cytochrome

Conflict of interest statement

Competing interests: J.D.P. is a scientific founder, a paid consultant and has equity in Dracen Pharmaceuticals.

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