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Sun, a member of �鶹�ƽ�� Division of Infectious Diseases and International Health, and colleagues found that serious viral infections can “reprogram” immune cells in the lungs in ways that may allow cancer tumors to develop months or even years later.

Based on their findings, researchers are urging doctors to closely monitor patients who have recovered from severe COVID-19, flu or pneumonia to help detect lung cancer early, when it is most treatable.

Setting the stage for lung cancer

Respiratory infections such as flu and COVID-19 often injure the lungs, but scientists have known little about the long-term cancer risks of those injuries. To explore the connection, Sun and his team studied both mice and human patients and found severe lung infections were linked to a higher risk of developing lung cancer – and dying from it.

Patient data showed a similar trend. People hospitalized with COVID-19 were more likely to develop lung cancer later, regardless of smoking history or other health conditions.

UVA School of Medicine researcher Jie Sun says a severe case of COVID-19 or flu can leave the lungs in a long-lasting “inflamed” state that makes it easier for cancer to take hold. (Photo by Erin Edgerton, University Communications)

“We’ve known for a long time that things like smoking increase the risk for lung cancer,” �鶹�ƽ�� Dr. Jeffrey Sturek, a collaborator on the project, said. “The results of this study suggest that we may need to consider severe respiratory viral infections similarly.”

Sturek said for some patients who are at high risk for lung cancer based on smoking history, doctors recommend close monitoring with routine screening CT scans of the lungs to catch cancer early. In future studies, doctors may want to consider a similar approach after severe respiratory viral infection.

Researchers say they may have figured out why severe lung infections could increase cancer risk. In mice, severe viral infections disrupted key immune cells that normally protect the lungs, leading to inflammation that can promote tumor growth. The infections also caused changes in the cells that line the lungs and air sacs.

Preventing long-term damage

The study also offered some reassuring news. Vaccination appeared to prevent these cancer-promoting changes, helping the immune system fight infections before they become severe. In patient data, the higher cancer risk showed up only in people hospitalized with severe COVID-19, not in those who had mild illness.

Still, researchers warn that many people who survived severe COVID-19 or other serious respiratory infections could face a higher risk of lung cancer in the years ahead.

“Individuals recovering from severe viral pneumonia, particularly those with a smoking history, may benefit from enhanced lung cancer surveillance,” . “And preventing severe infection through vaccination may confer indirect cancer protection benefits.”

Sun and his colleagues hope their findings will help doctors identify patients at risk of viral lung cancer, enabling them to receive treatment sooner.

“Our goal is to help doctors identify who may be at higher risk of lung cancer after a severe infection, and develop targeted ways to prevent and treat lung cancer after prior pneumonia,” Sun said. “We also believe that vaccines don’t just prevent acute hospitalization after contracting the virus; they may also reduce the long-term fallout of severe infection, including the kind of immune scarring that can increase cancer risk.”

The National Institutes of Health, a UVA Comprehensive Cancer Center Collaborative Grant, a UVA Pinn Scholar Award, a UVA Shannon Fellowship, a UVA Comprehensive Cancer Center Lung TRT Pilot Grant, an American Lung Association Catalyst Grant and a UVA Parsons-Weber-Parsons Fellowship supported the research.