# Fatal COVID-19 pulmonary disease involves ferroptosis

## TL;DR

The study finds that ferroptosis, an iron-dependent cell death, contributes to severe lung damage in fatal cases of COVID-19.

## Contribution

The paper identifies ferroptosis as a novel mechanism in severe COVID-19 lung disease and suggests potential therapeutic targets.

## Key findings

- Ferroptosis markers like transferrin receptor 1 and malondialdehyde are elevated in fatal COVID-19 lung autopsies.
- Iron overload promotes ferroptosis in lung epithelial cells and correlates with lung injury severity in a hamster model.
- Dysregulation of lipids and iron metabolism is observed in severe COVID-19 lung pathology.

## 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.

Ferroptosis is a form of cell death that has been associated with different diseases. Here the authors describe an association of ferroptosis with COVID-19 pulmonary pathologies in both patient samples and hamster model and suggest that the dysregulation in iron and lipid metabolism could provide targets to reduce pathology.