Promising Discovery Could Prevent Fatal COVID Lung Damage
Study reveals iron as a culprit, suggesting solutions that could help long COVID patients now and others in future viral pandemics
A subset of COVID patients experience severe lung damage, leading to fatalities, including 1,901 deaths worldwide over a one-month period ending in mid-May. While many organs are affected by the ever-growing number of variants that cause COVID-19, compromised lung function has been one of the most serious complications since the start of the pandemic in 2020.
New research from my lab, on human tissues and in hamsters, has shown how lungs are injured in COVID patients and how lung function can be preserved.
Meanwhile, the COVID pandemic has receded into the background noise of periodic colds, flus, and other mild illnesses, at least for many people around the world and for the media. But new variants of the virus that cause COVID-19 continue to spawn and circulate, and to cause serious and long-term debilitating illness in a subset of patients.
Just as the original SARS and MERS virus outbreaks in 2003 and 2012 receded from public discourse until the emergence of COVID-19 in 2020, a future variant or new virus may suddenly bring viral mechanisms and therapies into the world consciousness again — perhaps in 2029 if the trend continues. That’s why continuing to understand how these viruses cause damage to the body and how these health problems can be prevented remains a high priority.
Vast lung destruction during COVID
The actress Alyssa Milano is one of many people, prominent and otherwise, who were silently debilitated by the coronavirus. Milano told NBC New York that after she had COVID in 2020, she continued to experience shortness of breath, and that even two years later, her lungs had only 30% of their normal capacity.
Lung damage due to COVID makes it difficult to breathe, forcing the most severe COVID patients onto mechanical respirators to assist their breathing.
“Vast destruction of the architecture of the lungs,” is how Professor Mauro Giacca at King’s College London described the impact of COVID. Another frank assessment of the effects of COVID on the lungs by physician Howard Hang: “These lungs are not capable of sustaining life.”
Iron drives lung failure but provides a treatment
A new study from my group and our collaborators found that the lung damage during COVID is caused by activating a specific form of cell death driven by iron accumulation in cells of the lung. This type of cell death is known as ferroptosis, from the Latin ”ferrum” for iron combined with the suffix -ptosis, derived from the Greek word for falling away and for cell death processes.
We found that iron accumulates in lung cells and activates ferroptosis, leading to lung destruction and impaired breathing capacity. We found evidence of ferroptosis both in lung samples from patients who died of severe COVID and in a hamster model of COVID infection.
Ferroptosis can be prevented by specific treatments. Such ferroptosis-blocking drugs prevented lung damage in a hamster model of COVID — this suggests that people with COVID and similar viral infections could benefit from these drugs in the future. We also found that olive oil can prevent ferroptosis in cells and in mice in some cases, indicating that future research could examine whether diets rich in olive oil protect lungs against COVID damage in people.
COVID affects other organs as well — such as the brain, heart, kidneys and blood. The health consequences in these other organs may depend on other biological processes and require other treatments, or perhaps ferroptosis may be relevant to some of these organs as well. More research is needed to determine how damage happens in each organ during COVID.
While many people may agree with the World Health Organization’s statement that the pandemic emergency is over, more study is needed to treat the 6.4% of US adults who have reported experiencing long COVID, according to the CDC, as well as future pandemic victims.
Ongoing research will benefit people suffering from long COVID today, but the work will be even more important in the likely deadly pandemics that will come in the future. Many experts have said the recent pandemic is unlikely to be the worst humanity will face, given the increasing use of industrial agriculture coupled with climate change and integration of populations through globalization.
A future pandemic could have 20 times the fatalities of COVID, according to Tedros Adhanom Ghebreyesus, director-general of the World Health Organization. Now is the time to develop new treatments against viral infections and the damage they cause in the body, as this research takes years to lead to new therapies. Ferroptosis provides a new piece of the COVID puzzle that can help to advance effective treatments.
