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Fatal COVID-19 pulmonary disease involves ferroptosis

Author

Listed:
  • Baiyu Qiu

    (Columbia University)

  • Fereshteh Zandkarimi

    (Columbia University
    Columbia University)

  • Anjali Saqi

    (Columbia University Irving Medical Center)

  • Candace Castagna

    (Columbia University Irving Medical Center)

  • Hui Tan

    (Columbia University)

  • Miroslav Sekulic

    (Columbia University Irving Medical Center)

  • Lisa Miorin

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Hanina Hibshoosh

    (Columbia University Irving Medical Center)

  • Shinya Toyokuni

    (Nagoya University Graduate School of Medicine
    Nagoya University)

  • Koji Uchida

    (The University of Tokyo)

  • Brent R. Stockwell

    (Columbia University
    Columbia University Irving Medical Center
    Columbia University)

Abstract

SARS-CoV-2 infection causes severe pulmonary manifestations, with poorly understood mechanisms and limited treatment options. Hyperferritinemia and disrupted lung iron homeostasis in COVID-19 patients imply that ferroptosis, an iron-dependent cell death, may occur. Immunostaining and lipidomic analysis in COVID-19 lung autopsies reveal increases in ferroptosis markers, including transferrin receptor 1 and malondialdehyde accumulation in fatal cases. COVID-19 lungs display dysregulation of lipids involved in metabolism and ferroptosis. We find increased ferritin light chain associated with severe COVID-19 lung pathology. Iron overload promotes ferroptosis in both primary cells and cancerous lung epithelial cells. In addition, ferroptosis markers strongly correlate with lung injury severity in a COVID-19 lung disease model using male Syrian hamsters. These results reveal a role for ferroptosis in COVID-19 pulmonary disease; pharmacological ferroptosis inhibition may serve as an adjuvant therapy to prevent lung damage during SARS-CoV-2 infection.

Suggested Citation

  • Baiyu Qiu & Fereshteh Zandkarimi & Anjali Saqi & Candace Castagna & Hui Tan & Miroslav Sekulic & Lisa Miorin & Hanina Hibshoosh & Shinya Toyokuni & Koji Uchida & Brent R. Stockwell, 2024. "Fatal COVID-19 pulmonary disease involves ferroptosis," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48055-0
    DOI: 10.1038/s41467-024-48055-0
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    References listed on IDEAS

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    1. Johannes C. Melms & Jana Biermann & Huachao Huang & Yiping Wang & Ajay Nair & Somnath Tagore & Igor Katsyv & André F. Rendeiro & Amit Dipak Amin & Denis Schapiro & Chris J. Frangieh & Adrienne M. Luom, 2021. "Author Correction: A molecular single-cell lung atlas of lethal COVID-19," Nature, Nature, vol. 598(7882), pages 2-2, October.
    2. Johannes C. Melms & Jana Biermann & Huachao Huang & Yiping Wang & Ajay Nair & Somnath Tagore & Igor Katsyv & André F. Rendeiro & Amit Dipak Amin & Denis Schapiro & Chris J. Frangieh & Adrienne M. Luom, 2021. "A molecular single-cell lung atlas of lethal COVID-19," Nature, Nature, vol. 595(7865), pages 114-119, July.
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