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Metabolic programs define dysfunctional immune responses in severe COVID-19 patients.
Thompson, Elizabeth A; Cascino, Katherine; Ordonez, Alvaro A; Zhou, Weiqiang; Vaghasia, Ajay; Hamacher-Brady, Anne; Brady, Nathan R; Sun, Im-Hong; Wang, Rulin; Rosenberg, Avi Z; Delannoy, Michael; Rothman, Richard; Fenstermacher, Katherine; Sauer, Lauren; Shaw-Saliba, Kathyrn; Bloch, Evan M; Redd, Andrew D; Tobian, Aaron A R; Horton, Maureen; Smith, Kellie; Pekosz, Andrew; D'Alessio, Franco R; Yegnasubramanian, Srinivasan; Ji, Hongkai; Cox, Andrea L; Powell, Jonathan D.
  • Thompson EA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Cascino K; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Ordonez AA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Zhou W; Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA.
  • Vaghasia A; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Hamacher-Brady A; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA.
  • Brady NR; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA.
  • Sun IH; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Wang R; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Rosenberg AZ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Delannoy M; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Rothman R; Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Fenstermacher K; Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Sauer L; Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Shaw-Saliba K; Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Bloch EM; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Redd AD; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Baltimore, MD 21205, USA.
  • Tobian AAR; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Horton M; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Smith K; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Pekosz A; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA.
  • D'Alessio FR; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Yegnasubramanian S; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore
  • Ji H; Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA.
  • Cox AL; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore,
  • Powell JD; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: jpowell@jhmi.edu.
Cell Rep ; 34(11): 108863, 2021 03 16.
Article in English | MEDLINE | ID: covidwho-1108116
ABSTRACT
It is unclear why some SARS-CoV-2 patients readily resolve infection while others develop severe disease. By interrogating metabolic programs of immune cells in severe and recovered coronavirus disease 2019 (COVID-19) patients compared with other viral infections, we identify a unique population of T cells. These T cells express increased Voltage-Dependent Anion Channel 1 (VDAC1), accompanied by gene programs and functional characteristics linked to mitochondrial dysfunction and apoptosis. The percentage of these cells increases in elderly patients and correlates with lymphopenia. Importantly, T cell apoptosis is inhibited in vitro by targeting the oligomerization of VDAC1 or blocking caspase activity. We also observe an expansion of myeloid-derived suppressor cells with unique metabolic phenotypes specific to COVID-19, and their presence distinguishes severe from mild disease. Overall, the identification of these metabolic phenotypes provides insight into the dysfunctional immune response in acutely ill COVID-19 patients and provides a means to predict and track disease severity and/or design metabolic therapeutic regimens.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Immunity Type of study: Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged / Young adult Language: English Journal: Cell Rep Year: 2021 Document Type: Article Affiliation country: J.celrep.2021.108863

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Immunity Type of study: Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged / Young adult Language: English Journal: Cell Rep Year: 2021 Document Type: Article Affiliation country: J.celrep.2021.108863