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Metabolic imbalance of T cells in COVID-19 is hallmarked by basigin and mitigated by dexamethasone.
Siska, Peter J; Decking, Sonja-Maria; Babl, Nathalie; Matos, Carina; Bruss, Christina; Singer, Katrin; Klitzke, Jana; Schön, Marian; Simeth, Jakob; Köstler, Josef; Siegmund, Heiko; Ugele, Ines; Paulus, Michael; Dietl, Alexander; Kolodova, Kristina; Steines, Louisa; Freitag, Katharina; Peuker, Alice; Schönhammer, Gabriele; Raithel, Johanna; Graf, Bernhard; Geismann, Florian; Lubnow, Matthias; Mack, Matthias; Hau, Peter; Bohr, Christopher; Burkhardt, Ralph; Gessner, Andre; Salzberger, Bernd; Wagner, Ralf; Hanses, Frank; Hitzenbichler, Florian; Heudobler, Daniel; Lüke, Florian; Pukrop, Tobias; Herr, Wolfgang; Wolff, Daniel; Spang, Rainer; Poeck, Hendrik; Hoffmann, Petra; Jantsch, Jonathan; Brochhausen, Christoph; Lunz, Dirk; Rehli, Michael; Kreutz, Marina; Renner, Kathrin.
  • Siska PJ; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
  • Decking SM; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
  • Babl N; Regensburg Center for Interventional Immunology, University of Regensburg, Regensburg, Germany.
  • Matos C; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
  • Bruss C; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
  • Singer K; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
  • Klitzke J; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
  • Schön M; Department of Otorhinolaryngology, University Hospital Regensburg, Regensburg.
  • Simeth J; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
  • Köstler J; Department of Statistical Bioinformatics, Institute of Functional Genomics, University of Regensburg, Regensburg, Germany.
  • Siegmund H; Department of Statistical Bioinformatics, Institute of Functional Genomics, University of Regensburg, Regensburg, Germany.
  • Ugele I; Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany.
  • Paulus M; Institute of Pathology, University of Regensburg, Regensburg, Germany.
  • Dietl A; Central Biobank Regensburg, University Hospital and University of Regensburg, Regensburg, Germany.
  • Kolodova K; Department of Otorhinolaryngology, University Hospital Regensburg, Regensburg.
  • Steines L; Department of Internal Medicine II.
  • Freitag K; Department of Internal Medicine II.
  • Peuker A; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
  • Schönhammer G; Regensburg Center for Interventional Immunology, University of Regensburg, Regensburg, Germany.
  • Raithel J; Department of Nephrology.
  • Graf B; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
  • Geismann F; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
  • Lubnow M; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
  • Mack M; Regensburg Center for Interventional Immunology, University of Regensburg, Regensburg, Germany.
  • Hau P; Department of Anesthesiology.
  • Bohr C; Department of Internal Medicine II.
  • Burkhardt R; Department of Internal Medicine II.
  • Gessner A; Department of Nephrology.
  • Salzberger B; Wilhelm Sander-NeuroOncology Unit and Department of Neurology.
  • Wagner R; Department of Otorhinolaryngology, University Hospital Regensburg, Regensburg.
  • Hanses F; Institute of Clinical Chemistry and Laboratory Medicine.
  • Hitzenbichler F; Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany.
  • Heudobler D; Department of Infection Prevention and Infectious Diseases, and.
  • Lüke F; Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany.
  • Pukrop T; Department of Infection Prevention and Infectious Diseases, and.
  • Herr W; Emergency Department, University Hospital Regensburg, Regensburg, Germany.
  • Wolff D; Department of Infection Prevention and Infectious Diseases, and.
  • Spang R; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
  • Poeck H; Bavarian Cancer Research Center, Regensburg, Germany.
  • Hoffmann P; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
  • Jantsch J; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
  • Brochhausen C; Bavarian Cancer Research Center, Regensburg, Germany.
  • Lunz D; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
  • Rehli M; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
  • Kreutz M; Regensburg Center for Interventional Immunology, University of Regensburg, Regensburg, Germany.
  • Renner K; Department of Statistical Bioinformatics, Institute of Functional Genomics, University of Regensburg, Regensburg, Germany.
J Clin Invest ; 131(22)2021 11 15.
Article in English | MEDLINE | ID: covidwho-1518200
ABSTRACT
Metabolic pathways regulate immune responses and disrupted metabolism leads to immune dysfunction and disease. Coronavirus disease 2019 (COVID-19) is driven by imbalanced immune responses, yet the role of immunometabolism in COVID-19 pathogenesis remains unclear. By investigating 87 patients with confirmed SARS-CoV-2 infection, 6 critically ill non-COVID-19 patients, and 47 uninfected controls, we found an immunometabolic dysregulation in patients with progressed COVID-19. Specifically, T cells, monocytes, and granulocytes exhibited increased mitochondrial mass, yet only T cells accumulated intracellular reactive oxygen species (ROS), were metabolically quiescent, and showed a disrupted mitochondrial architecture. During recovery, T cell ROS decreased to match the uninfected controls. Transcriptionally, T cells from severe/critical COVID-19 patients showed an induction of ROS-responsive genes as well as genes related to mitochondrial function and the basigin network. Basigin (CD147) ligands cyclophilin A and the SARS-CoV-2 spike protein triggered ROS production in T cells in vitro. In line with this, only PCR-positive patients showed increased ROS levels. Dexamethasone treatment resulted in a downregulation of ROS in vitro and T cells from dexamethasone-treated patients exhibited low ROS and basigin levels. This was reflected by changes in the transcriptional landscape. Our findings provide evidence of an immunometabolic dysregulation in COVID-19 that can be mitigated by dexamethasone treatment.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Dexamethasone / T-Lymphocytes / Basigin / SARS-CoV-2 / COVID-19 Limits: Adult / Female / Humans / Male / Middle aged Language: English Year: 2021 Document Type: Article Affiliation country: JCI148225

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Dexamethasone / T-Lymphocytes / Basigin / SARS-CoV-2 / COVID-19 Limits: Adult / Female / Humans / Male / Middle aged Language: English Year: 2021 Document Type: Article Affiliation country: JCI148225