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First-of-its-kind Study Shows That COVID-19 Can Result in Irreversible Lung Damage Requiring Lung Transplantation

Chicago, IL – For the first time, researchers found that COVID-19 can destroy the fundamental framework of the lungs, rendering them irrecoverable, and lung transplantation is the only option for survival. A new Northwestern Medicine study published in Science Translational Medicine* discovered that COVID-19 causes permanent damage and severe scarring to the lungs, mimicking that observed in patients with pulmonary fibrosis, resulting in the need for a lung transplant. Using lung tissue from Northwestern Medicine patients who underwent lung transplants due to COVID-19 and autopsies from patients who died from the virus, researchers found compelling changes which shed light into the catastrophic effects the virus has on human lungs. The study also discovered unique cells, KRT17 epithelial cells, in the lung tissue of patients with irreversible damage that have also been observed in patients with end stage pulmonary fibrosis.

“We provide explicit evidence that COVID-19 can cause permanent damage to the lung in some patients for whom lung transplantation is the only hope for survival,” says Ankit Bharat, MD, chief of thoracic surgery and surgical director of the Northwestern Medicine Lung Transplant Program, and the principal investigator of the study. “The progenitor cells in the lungs necessary for healing can repopulate wounds of the lung by moving along the basic underlying framework of the lung matrix. But when the framework is destroyed, the progenitor cells have no place to go and lungs develop large holes that serve to harbor infections, an observation we also made during the tough transplant surgeries in these patients. Think of it this way: after an earthquake, if the basic structure of a building survives, it can still be refurbished. However, if it is levelled, the only option is replacement.”

Additional study results include:
- It is safe to perform lung transplantation on critically ill patients, even those suffering from infectious causes of lung failure such as COVID-19, a new paradigm in transplantation.
- Despite the use of immunosuppressive medications, COVID-19 virus and other hospital acquired infections that existed in the patients do not come back.
- There is permanent and irrecoverable damage to the lungs in some COVID-19 patients and without transplantation, the patients would not survive.
- It is safe to support the patients for extended durations on ECMO support and then successfully transplant them.
- Following transplant and removal of the damaged lungs, the patients recover at a rapid pace.

Using highly sophisticated scientific tools, researchers dissected the discarded lungs removed from the first patients in the United States who received lung transplants due to COVID-19, as well as lungs from patients who died from the virus, in order to study the expression of genes of thousands of individual cells belonging to all different types. Then, using machine learning and artificial intelligence, those expression profiles of COVID-19 lungs were “mapped” onto atlases developed from normal lungs or the lungs of patients who required transplantation for other chronic conditions. This led to the discovery of unique epithelial cells which mark permanent areas of injury and mechanisms which cause permanent lung scarring. Researchers are hopeful these can be used to identify patients who are unlikely to heal and might need lung transplantation.

“The lungs affected by COVID-19 also showed striking similarities to the lungs of patients with a condition called idiopathic pulmonary fibrosis – which causes lung tissue to get thick and stiff, making it difficult for the body to take in oxygen,” explains Scott Budinger, MD, Ernest S. Bazley professor and chief of pulmonary and critical care medicine at Northwestern Medicine, and senior author of the study. “As in pulmonary fibrosis, we found that COVID-19 led to the recruitment of circulating immune cells called monocytes which are likely recruited to the lung to kill the virus. In the fibrotic lung, these cells also promote the formation of fibrotic scar tissue. These cells can be easily and safely sampled and might also help mark patients who are failing to recover from COVID-19.”

In June, Northwestern Medicine surgeons performed the first known double-lung transplant on a COVID-19 patient in the United States. To date, eight COVID-19 patients have received double-lung transplants at Northwestern Medicine – the most performed at any health system in the world. The most recent transplant happened on Thanksgiving Day for a critically ill patient who spent 130 days on extracorporeal membrane oxygenation (ECMO), a life support machine that does the work of the heart and lungs. It’s the longest known amount of time a patient has spent on ECMO in the world before receiving a transplant.

“With about 5.5 million active COVID-19 infections currently in the U.S. and thousands of new cases daily, the need for lung transplantation will grow,” adds Dr. Bharat. “By using information from our study, we hope more patients can receive lung transplants and that new treatments will be developed to prevent permanent lung damage from viruses.”

To read the full study, visit Science Translational Medicine*