A recent study has shed light on the mystery of why, in some severe Covid-19 cases, the lungs undergo extreme damage, resulting in various life-threatening conditions like pneumonia, inflammation, and acute respiratory distress syndrome.
The root cause of those wide-ranging reactions has remained unclear, until now.
Researchers at Columbia and the Columbia University Irving Medical Centre have discovered that ferroptosis, a form of cell death first named and identified at Columbia in 2012, is the major cell death mechanism that underlies this particular lung disease.
Their finding – published in Nature Communications – indicates that deliberately halting ferroptosis with therapeutic drug candidates could improve Covid-19 outcomes.
“This adds crucial insight to our understanding of how Covid affects the body, and will significantly improve our ability to fight life-threatening cases of the disease,” said Professor Brent Stockwell, one of the study’s lead authors.
Ferroptosis, which was first reported by Stockwell in 2012, occurs when certain cells die because their outer fat layers collapse.
It differs from the most common kind of cell death, when both in disease contexts and in normal processes like ageing, involves cells chopping up the molecules in their interior.
Since proposing the concept of ferroptosis, Stockwell’s lab has demonstrated that it is instrumental to normal bodily processes, but that it can also attack and kill healthy cells in patients with neurodegenerative diseases like Parkinson’s, Alzheimer’s, and Lou Gehrig’s disease.
Though ferroptosis can be destructive, recent studies indicate that it could also be harnessed for good.
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 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.
Study details
Fatal COVID-19 pulmonary disease involves ferroptosis
Baiyu Qiu, Fereshteh Zandkarimi, Brent Stockwell et al.
Published in Nature Communications on 20 May 2024
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.
Nature Communications article – Fatal COVID-19 pulmonary disease involves ferroptosis (Open access)
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Long Covid breathlessness: Novel scans uncover hidden lung damage
Covid-19 sufferers’ lungs may be damaged ‘beyond recognition’
Impaired lung function in 25% of long Covid patients – Dutch study