Research News

COVID-19 infection activates a gene in the lungs that promotes lung damage and mucus production, according to new Cleveland Clinic and Michigan State University research. This progressive lung scarring can eventually lead to the need for a lung transplant.

The collaboration investigated the biology behind climbing lung transplant rates among patients with post-COVID pulmonary fibrosis. Almost ten percent of all lung transplants in the United States now go to COVID-19 patients, according to data from the United Network for Organ Sharing, or UNOS. Understanding how and why some individuals develop severe lifelong complications is critical to developing more effective post-COVID lung damage treatment. Kun Li, PhD, of Cleveland Clinic's Florida Research and Innovation Center, and MSU College of Human Medicine's Xiaopeng Li, PhD, discovered that SARS-CoV-2 infection increases expression of gene called ATP12A.

When the gene is turned on, it directly contributes to progressive lung scarring, excessive mucous production and impaired oxygen absorption. ATP12A can potentially serve as a diagnostic marker and a drug target, according to the findings published in American Journal of Respiratory Cell and Molecular Biology. 

Above: An image of lungs affected by post-COVID fibrosis, taken by a microscope. Blue dots represent the nuclei of different lung cells. Red areas indicate where APT12A is turned "on" along the lining of the lung.

The results build on Dr. Xiaopeng Li's previous work on ATP12A, which he had already connected to excessive mucous production and lung damage in individuals with pulmonary fibrosis that isn't associated with COVID-19. He approached Dr. Kun Li, an expert in coronaviruses and post-COVID-19 complications, to further investigate whether fibrosis resulting from a virus would show the same connection.

At Michigan State University, Dr. Xiaopeng Li examined 18 lung samples from individuals undergoing transplant for pulmonary fibrosis. This was in collaboration with Dr. Reda Girgis, the medical director of the lung transplant program at Corewell Health and a Professor of Medicine at MSU. Dr. Xiaopeng Li confirmed individuals with fibrosis due to COVID-19 infection also had highly elevated levels of ATP12A, similarly to fibrosis not related to COVID. At Cleveland Clinic, Dr. Kun Li and postdoctoral fellow Shan Zhou, PhD, worked at the lab bench and confirmed COVID-19 infection directly caused ATP12A levels to increase and contributed to pulmonary fibrosis.

The next step is to determine how infection elevates APT12A levels and why elevated gene expression contributes to the lung damage characteristic of pulmonary fibrosis.

"We saw this connection not only in human lungs, but at the bench in preclinical work," Dr. Kun Li says. "Validating both is a strong foundation for moving these discoveries forward to treatments that could benefit all pulmonary fibrosis patients, regardless of if their condition came from COVID-19."