Metabolic imbalance of T cells in COVID-19 is hallmarked by basigin and mitigated by dexamethasone

J Clin Invest. 2021 Nov 15;131(22):e148225. doi: 10.1172/JCI148225.


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.

Keywords: Inflammation; Metabolism; Mitochondria; Monocytes; T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Basigin / physiology*
  • COVID-19 / immunology*
  • COVID-19 / metabolism
  • Cyclophilin A / physiology
  • Dexamethasone / pharmacology*
  • Fatty Acids / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitochondria / pathology
  • Reactive Oxygen Species / metabolism
  • SARS-CoV-2*
  • T-Lymphocytes / metabolism*


  • Fatty Acids
  • Reactive Oxygen Species
  • Basigin
  • Dexamethasone
  • Cyclophilin A