Severe COVID-19 or flu may raise lung cancer risk years later, study finds

A new study has found that people who survive severe COVID-19 or influenza infections face a meaningfully elevated risk of developing lung cancer in the years following their illness. The research, which analyzed lung tissue and immune cell behavior in both mouse models and human patient data, identified a specific biological mechanism: serious viral infections can reprogram immune cells in the lungs into a state of chronic inflammation that persists long after the virus itself is gone, and that sustained inflammatory environment appears to accelerate the growth of precancerous lung cells.

The finding is not that viral infections cause cancer directly. What the study describes is a conditional risk elevation. Lung tissue already carrying microscopic precancerous changes, which are present in a significant portion of middle-aged and older adults who have never been diagnosed with cancer, appears to progress to malignancy faster in patients whose immune systems were significantly disrupted by severe respiratory viral illness. The inflammation does not create the cancer seed. It speeds up how quickly it grows.

The immune mechanism the researchers identified

The study focused on a class of immune cells called interstitial macrophages, which reside permanently in lung tissue and help regulate the local immune environment. In healthy lungs, these macrophages maintain a state that suppresses excessive inflammation and controls tissue repair. The researchers found that after severe COVID-19 or influenza infection, a subset of these macrophages undergoes a lasting change in gene expression, shifting toward a pro-inflammatory state that produces elevated levels of cytokines including IL-6, TNF-alpha, and CCL2 for months or years after infection.

Elevated IL-6 and TNF-alpha are not benign bystanders. IL-6 activates the STAT3 signaling pathway in nearby epithelial cells, and chronic STAT3 activation is well established in oncology literature as a driver of cancer cell proliferation and survival. A 2022 meta-analysis published in the journal Oncogene reviewed 47 studies and found that elevated IL-6 levels in lung tissue were associated with a 2.3-fold increase in lung cancer incidence across the populations studied. The new study's finding that severe viral infections lock macrophages into a persistent IL-6-producing state provides a direct link between the infection history and that elevated cancer risk.

How much does severe infection actually raise lung cancer risk

The human cohort analysis in the study drew on electronic health records from 320,000 patients in the UK Biobank and a separate cohort of 180,000 patients from the US Veterans Affairs health system. Among patients who had been hospitalized for severe COVID-19 or influenza pneumonia, the hazard ratio for lung cancer diagnosis over the following five years was 1.47 compared to matched controls with no severe respiratory viral illness. Translated to plain language, that means a 47 percent higher relative risk of lung cancer diagnosis, not a 47 percent absolute chance of developing lung cancer.

The absolute risk numbers are more grounding. Lung cancer develops in approximately 0.5 percent of the general non-smoking population over any given five-year period. A 47 percent relative increase raises that figure to approximately 0.74 percent. For current or former smokers, whose baseline lung cancer risk is considerably higher, the same relative increase translates to a more significant absolute number. Among heavy smokers in the study cohort who had also been hospitalized with severe viral pneumonia, the five-year lung cancer incidence was 3.1 percent, compared to 2.1 percent in heavy smokers without severe infection history.

Why COVID-19 and influenza produce similar effects

One of the study's notable findings is that severe COVID-19 and severe influenza produced statistically similar elevations in lung cancer risk, with no significant difference between the two viruses in the hazard ratio estimates. The researchers interpret this as evidence that the underlying mechanism is not specific to SARS-CoV-2 biology but rather a general consequence of severe viral pneumonia that damages and reprograms lung macrophages regardless of which virus caused the infection.

The severity threshold matters significantly. Patients who had mild or moderate COVID-19 or influenza, defined in the study as infections managed without hospitalization, showed no statistically significant elevation in lung cancer risk at five years. The risk elevation was confined to patients who required inpatient hospital care, and it increased with length of hospital stay. Patients hospitalized for more than 14 days showed a hazard ratio of 1.71 compared to 1.31 for patients hospitalized for fewer than 7 days, suggesting a dose-response relationship between the severity of the immune disruption and the subsequent cancer risk.

The vaccination finding and what it means practically

The most clinically actionable part of the study is the vaccination data. Among patients who had received COVID-19 vaccination before their severe COVID-19 infection, the five-year lung cancer hazard ratio dropped to 1.18, compared to 1.52 in unvaccinated patients who experienced severe COVID-19. For influenza, patients who had received the seasonal flu vaccine in the year of their severe influenza infection had a hazard ratio of 1.14, compared to 1.44 in unvaccinated patients with severe influenza. The vaccine effect does not eliminate the elevated risk entirely, but it attenuates it substantially.

The researchers hypothesize that vaccination reduces the severity of the initial immune response to infection, limiting the degree of macrophage reprogramming that occurs during the acute illness phase. A less severe cytokine storm during acute infection means less lasting disruption to the lung's immune regulatory environment, which translates to less persistent inflammation in the recovery period. This mechanism, if confirmed in further studies, would make a straightforward case for vaccination as a partial cancer prevention strategy in populations at elevated baseline lung cancer risk, particularly heavy smokers and former smokers.

Limitations of the study and what still needs to be answered

The study is observational, which means it can identify associations but cannot definitively prove causation. People who are hospitalized with severe viral pneumonia differ from those who are not in multiple ways, including age, pre-existing health conditions, smoking history, air pollution exposure, and access to healthcare. The researchers used propensity score matching to adjust for known confounders, but residual confounding from unmeasured variables cannot be excluded. In particular, patients hospitalized with severe viral illness may have been exposed to CT chest scans that incidentally detected early lung cancers that would not otherwise have been found within the five-year study window.

The study was published in the journal Nature Medicine in February 2026 and was conducted by a collaboration between the Francis Crick Institute in London, University College London, and Stanford University School of Medicine. The research team has proposed a prospective follow-up study that would track lung macrophage inflammatory markers in severe COVID-19 and influenza survivors over five years and correlate those markers with CT-confirmed lung lesion progression, with enrollment planned to begin at UCL Hospital in the third quarter of 2026.