How Severe COVID and Flu Infections Raise Lung Cancer Risk

A Surprising Link Between Viral Illness and Cancer

Most people who survive a serious bout of COVID-19 or influenza expect to recover and move on. But emerging research reveals a troubling aftereffect: a severe respiratory viral infection can quietly rewire the immune landscape of the lungs, making them significantly more hospitable to cancer—months or even years after the illness itself has resolved.

A landmark study published in the journal Cell by researchers at the University of Virginia found that patients hospitalized with COVID-19 face a 1.24-fold increase in lung cancer incidence compared to those who were never severely infected—regardless of smoking history or pre-existing health conditions. The findings represent a major shift in how physicians may need to think about post-infection care.

What Happens Inside the Lung After Severe Infection

The mechanism is rooted in the immune system's response to extreme stress. During a severe viral pneumonia, the lungs deploy vast numbers of immune cells—particularly neutrophils and macrophages—to fight off the infection. In mild cases, these soldiers clean up and stand down. In severe cases, they don't fully recover.

Researchers discovered that serious infections epigenetically reprogram these immune cells, essentially altering which genes are switched on and off without changing the underlying DNA sequence. The result is a class of dysfunctional neutrophils that linger in the lungs long after the virus has been cleared. Instead of protecting tissue, they secrete pro-inflammatory signals that create what scientists describe as a "pro-tumor microenvironment"—conditions that actively assist cancer cells in taking hold and multiplying.

Cells lining the lungs and air sacs (alveolar epithelial cells) also sustain significant damage, further compromising the lung's ability to suppress abnormal cell growth. As Dr. Jie Sun of UVA's Carter Immunology Center put it: "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."

Severity Is the Key Factor

Crucially, the elevated cancer risk was observed only in severe cases—those requiring hospitalization. Patients who experienced mild COVID-19 infections actually showed a slight decrease in lung cancer risk, possibly because a controlled immune response strengthens surveillance against abnormal cells. This distinction matters: it is not the virus itself, but the magnitude of immune disruption it triggers, that drives the downstream cancer risk.

The pattern held true in both animal models and human patient data. In laboratory mice, severe lung viral infection significantly increased both the likelihood of developing lung tumors and mortality from the disease. When researchers analyzed human cohort data, the same relationship emerged across different demographic groups and health backgrounds.

How Chronic Inflammation Fuels Cancer

The connection between chronic inflammation and cancer is well established in oncology. Persistent inflammation generates oxidative stress, which damages DNA; promotes genomic instability, giving pre-cancerous cells room to mutate; and suppresses the normal immune surveillance that would otherwise detect and eliminate rogue cells.

What this new research adds is a specific, traceable cellular pathway: tumor-associated neutrophils (a subtype researchers call SiglecF-high neutrophils) accumulate in post-infection lungs and actively suppress anti-tumor immunity. This gives any nascent cancer cells a window of vulnerability in the host's defenses—and they exploit it.

What This Means for Patients and Clinicians

The findings have direct clinical implications. Researchers recommend that survivors of severe respiratory viral infections—particularly smokers or those with other known lung cancer risk factors—be considered for enhanced surveillance, including routine low-dose computed tomography (CT) screening of the lungs. Dr. Jeffrey Sturek of UVA suggests the field may need to classify severe respiratory viral infection as a risk factor for lung cancer, comparable to prolonged smoking exposure.

The encouraging counterweight is vaccination. In both mouse models and human data analysis, prior vaccination against COVID-19 or influenza largely prevented the harmful epigenetic reprogramming of immune cells. Vaccinated individuals who did get infected tended to have milder illness—and avoided the pro-tumor immune changes altogether. This reframes vaccination not merely as protection against the acute infection, but as an indirect cancer-prevention strategy.

The Bigger Picture

This research fits into a growing body of evidence that viral infections can shape long-term cancer trajectories. Human papillomavirus (HPV) drives cervical and throat cancers; hepatitis B and C viruses drive liver cancer; Epstein-Barr virus is linked to several lymphomas. Respiratory viruses like influenza and SARS-CoV-2 had not been firmly placed in this category until now.

For the hundreds of millions of people who experienced severe COVID-19 during the pandemic, the message is not alarm—but awareness. Knowing the mechanism opens the door to targeted screening programs and, potentially, therapies aimed at reversing the immune reprogramming before a tumor ever has the chance to form.