Severe COVID-19 and Flu Linked to Increased Lung Cancer Risk, Vaccination Offers Protection

Severe cases of COVID-19 or the flu may leave a lasting mark on the lungs that increases the risk of lung cancer later, but vaccines appear to stop the damage before it starts. New research from UVA Health’s Beirne B. Carter Center for Immunology Research and the UVA Comprehensive Cancer Center suggests that serious viral infections can create conditions in the lungs that make cancer more likely to develop.

Long-Term Impact of Viral Infections on Lung Health

Researchers at the University of Virginia School of Medicine, led by Jie Sun, PhD, discovered that severe viral infections can alter immune cells in the lungs in ways that promote tumor growth months or even years afterward. The study, published in Cell, highlights the importance of monitoring patients who have recovered from severe respiratory illnesses.

“A bad case of COVID or flu can leave the lungs in a long-lasting ‘inflamed’ state that makes it easier for cancer to take hold later,” said Sun, co-director of UVA’s Carter Center and a member of UVA’s Division of Infectious Diseases and International Health. “The encouraging news is that vaccination largely prevents those harmful changes for cancer growth in the lung.”

How Viral Infections Increase Lung Cancer Risk

Respiratory illnesses like influenza and COVID-19 are known causes of lung injury. However, the long-term effects on cancer risk haven’t been fully understood. Sun and colleagues studied the effects of severe infections in both laboratory mice and human patients.

The findings revealed that mice with severe lung infections were more likely to develop lung cancer and die from the disease. A similar pattern was observed in patient data, with individuals hospitalized with COVID-19 showing a higher rate of lung cancer diagnoses. Hospitalization for COVID-19 was associated with a 1.24-fold increase in lung cancer risk, regardless of smoking history or other health conditions.

“These findings have critical immediate implications for how we monitor patients after severe respiratory viral infection,” said Jeffrey Sturek, MD, PhD, a UVA physician-scientist who collaborated on the study. “We’ve known for a long time that things like smoking increase the risk for lung cancer. The results from this study suggest that we may need to think about severe respiratory viral infection similarly. For example, in some patients who are at high risk for lung cancer based on smoking history, we recommend close monitoring with routine screening CT scans of the lungs to catch cancer early. In future studies, we may want to consider a similar approach after severe respiratory viral infection.”

Immune Cell Changes and Tumor Growth

Experiments in mice revealed that severe viral infections cause changes in immune cells called neutrophils and macrophages, which normally protect lung tissue. After infection, some neutrophils behaved abnormally, contributing to inflammation that favors tumor growth. Alterations were too observed in epithelial cells, which line the lungs and air sacs.

Vaccination as a Protective Measure

The research offers encouraging evidence that vaccination can block these harmful biological changes. Vaccines train the immune system to respond quickly to infections, reducing the severity of illness. The increased lung cancer risk was primarily seen in patients who experienced severe COVID-19, while those with mild cases showed a small decrease in risk.

Despite the protective effect of vaccination, the researchers caution that millions who survived severe COVID-19 or other serious respiratory infections could face an elevated risk of lung cancer in the future. “With tens of millions of people globally experiencing long-term pulmonary [COVID-19] sequelae, these findings carry significant implications for clinical care,” the scientists wrote in their paper.

Implications for Early Detection and Future Treatments

Sun and his team hope their work will help doctors identify patients at higher risk of lung cancer after severe viral infections, allowing for earlier screening and treatment. They also believe their findings could guide the development of new therapies to counteract the biological changes caused by severe lung infections.

“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.”