Over the past few years, researchers have uncovered countless details about how SARS-CoV-2 causes COVID-19. However, the mechanisms underlying how SARS-CoV-2 infection causes severe pulmonary manifestations remain poorly understood. This, in turn, limits treatment options.

In some severe cases of COVID-19, the lungs undergo extreme damage, resulting in a range of life-threatening conditions like pneumonia, inflammation, and acute respiratory distress syndrome. The root cause of those wide-ranging reactions in the lungs has remained unclear. However, hyperferritinemia and disrupted lung iron homeostasis in COVID-19 patients have pointed to ferroptosis—an iron-dependent cell death.

Now, a new study finds that ferroptosis is the major cell death mechanism that underlies COVID-19 lung disease. In a new paper, the authors noted that “immunostaining and lipidomic analysis in COVID-19 lung autopsies reveal increases in ferroptosis markers, including transferrin receptor 1 and malondialdehyde accumulation in fatal cases.” The finding indicates that deliberately halting ferroptosis with therapeutic drug candidates could improve COVID-19 outcomes.

This work is published in Nature Communications in the paper, “Fatal COVID-19 pulmonary disease involves ferroptosis.

“This finding adds crucial insight to our understanding of how COVID-19 affects the body that will significantly improve our ability to fight life-threatening cases of the disease,” said Brent Stockwell, PhD, chair of the department of biological sciences and a professor at Columbia University in the departments of biological science and chemistry.

COVID-19 lungs displayed dysregulation of lipids involved in metabolism and ferroptosis. The researchers found increased ferritin light chain associated with severe COVID-19 lung pathology. More specifically, the authors noted that “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.”

Ferroptosis was first reported by Stockwell in 2012. Ferroptosis differs from the most common kind of cell death, which occurs both in disease contexts and in normal processes like aging and involves cells chopping up the molecules in their interior.

Though ferroptosis can be destructive, recent studies indicate that intentionally inducing ferroptosis could counteract diseases like cancer where rampant cell growth is dangerously occurring. The ability to inhibit ferroptosis, on the other hand, could offer doctors new ways of combating cell death that should not be occurring, as in the case of COVID-19 lung disease.

“We’re hopeful that these important new findings could improve our ability to confront this pernicious disease, which, in too many cases, still diminishes health outcomes and results in death,” Stockwell said.

Previous articleAutoimmune Disease Prediction Boosted by AI
Next articleBud-wiser: DOD Backs A-Alpha Bio for Biothreat Preparation