A Bad Case of COVID or Flu May Raise Lung Cancer Risk Years Later

Severe COVID or flu may quietly raise lung cancer risk—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 severe cases of COVID-19 and influenza may create conditions in the lungs that make cancer more likely to develop later. The study also found that vaccination appears to prevent these harmful effects.

Researchers at the UVA School of Medicine, led by Jie Sun, PhD, discovered that serious viral infections can alter immune cells in the lungs in ways that promote tumor growth months or even years afterward. Based on these findings, the team recommends that doctors closely monitor patients who have recovered from severe COVID, flu, or pneumonia so lung cancer can be detected early, when treatment is most effective.

“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 Severe Viral Infections Can Set the Stage for Lung Cancer

Respiratory illnesses such as influenza and COVID are among the leading causes of lung injury. However, scientists have not fully understood how these injuries might affect cancer risk over the long term. To investigate, Sun and his colleagues studied the effects of severe infections in both laboratory mice and human patients.

The findings were striking. Mice that experienced severe lung infections were more likely to develop lung cancer later and were also more likely to die from the disease. When researchers examined patient data, they observed a similar pattern. Individuals who had previously been hospitalized with COVID-19 showed a higher rate of lung cancer diagnoses.

Overall, hospitalization for COVID-19 was associated with a 1.24-fold increase in lung cancer risk. This increase appeared regardless of whether patients smoked or had other health conditions, which doctors call “comorbidities.”

“These findings have important 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 Changes That Help Tumors Grow

Experiments in mice helped researchers understand why this increased risk occurs. Severe viral infections caused major changes in immune cells known as neutrophils and macrophages, which normally protect lung tissue.

After infection, some neutrophils behaved abnormally and contributed to a persistent inflammatory environment that favors tumor growth. Scientists also observed significant alterations in epithelial cells, the cells that line the lungs and the air sacs responsible for breathing.

Vaccination May Prevent Cancer-Promoting Lung Changes

The researchers found encouraging evidence that vaccination can block these harmful biological changes. Vaccines train the immune system to respond quickly to infections, which helps reduce how severe the illness becomes.

The increased lung cancer risk was seen in patients who experienced severe COVID-19, but not in those who had mild cases. In fact, people with mild infections showed a small decrease in risk.

Despite this protective effect, the researchers caution that millions of people 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. “Individuals recovering from severe viral pneumonia, particularly those with smoking history, may benefit from enhanced lung cancer surveillance, and preventing severe infection through vaccination may confer indirect cancer protection benefits.”

Implications for Early Detection and Future Treatments

Sun and his team hope their work will help doctors identify patients who may face a higher risk of lung cancer after severe viral infections. Earlier identification could allow patients to receive screening and treatment sooner.

The researchers also believe their findings could guide the development of new therapies aimed at counteracting 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.”

Reference: 11 March 2026, Cell.

The findings were published in the scientific journal Cell.

The research team included Wei Qian, Xiaoqin Wei, Andrew J. Barros, Xiangyu Ye, Haibo Zhang, Qing Yu, Samuel P. Young, Eric V Yeatts, Yury Park, Chaofan Li, Sijie Hao, Gislane Almeida-Santos, Jinyi Tang, Harish Narasimhan, Nicole A Kirk, Valeria Molinary, Ying Li, Li Li, Bimal N. Desai, Peter Chen, Kwon-Sik Park, Anny Xiaobo, Jeffrey M. Sturek, Wei Chen, In Su Cheon, and Sun.

Understanding and treating complex diseases is a major focus of UVA’s Paul and Diane Manning Institute of Biotechnology. The institute works to accelerate discoveries like Sun’s research and translate them more quickly into new medical treatments that can save lives.

UVA’s Beirne B. Carter Center for Immunology Research (CIC) was established through the generosity of Beirne B. Carter, and the Beirne Carter Foundation continues to support its work. CIC scientists study infections, cancer, cardiovascular disease, chronic lung conditions, the microbiome, and autoimmune disorders to advance new therapies and cures.

The UVA Comprehensive Cancer Center is one of only 57 cancer centers nationwide to receive the National Cancer Center’s “comprehensive” designation, recognizing excellence in patient care and innovative cancer research.

Funding for the research came from the National Institutes of Health, grants AI147394, AG069264, AI112844, HL170961, AI176171, AG090337, R01HL179312, F31HL170746, T32AI007496, T32CA009109, R01AI155808 and R01HL162783; a UVA Comprehensive Cancer Center Collaborative Grant, U01CA224293; a UVA Pinn Scholar Award; a UVA Shannon Fellowship; a UVA Comprehensive Cancer Center Lung TRT Pilot Grant; an American Lung Association Catalyst Grant, T32GM139787-01; and a UVA Parsons-Weber-Parsons Fellowship.

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