New research from scientists at Marshall University and The Hebrew University of Jerusalem suggests COVID-19 may be associated with biological changes in the lungs that could increase the risk of lung cancer over time, particularly among current and former smokers.
The study, published in Frontiers in Immunology, combined clinical data with laboratory and animal research to examine how SARS-CoV-2, the virus that causes COVID-19, may affect long-term lung health.
Researchers cautioned that the study does not prove COVID-19 directly causes lung cancer. The clinical portion relied on a retrospective review of medical records, which can identify associations but cannot establish cause and effect.
Higher Rates Found In Patient Records
Using the TriNetX Research Network, researchers analyzed matched patient records by smoking status and found higher rates of lung cancer among patients with a documented history of COVID-19.
Among current smokers, lung cancer developed in 1.7% of people with prior COVID-19, compared with 1.4% of those without a documented history of infection. Among former smokers, the rates were 1.5% and 1.2%, respectively. Researchers also found a smaller statistically significant increase among people who had never smoked.
“Our findings suggest that COVID-19 may do more than cause acute illness—it may also create biological conditions in the lung that could contribute to increased cancer risk over time,” said Wei Li, Ph.D., professor of biomedical sciences at Marshall University’s Joan C. Edwards School of Medicine and co-corresponding author of the study. “Understanding these pathways is critical as we continue to study the long-term health impacts of the virus.”
Researchers Point To Possible Lung Changes
The research focused on thymidine phosphorylase, or TYMP, a protein researchers said may interact with the SARS-CoV-2 spike protein and promote inflammation, fibrosis, and tumor-related pathways in the lungs.
In mouse studies, researchers found that spike protein exposure contributed to lung injury, inflammatory responses, and tiny blood clots known as microthrombi. Those effects were reduced in mice lacking TYMP.
Researchers also found that spike protein exposure increased tumor development in a mouse model of lung cancer. Tumors appeared in 50% of lung lobes examined in spike-treated mice with TYMP, compared with 18% in spike-treated mice lacking TYMP.
“The collaboration between basic and translational scientists and clinicians enabled the identification of mechanisms underlying epidemiological evidence linking COVID-19 infection to the potential increased risk of lung cancer,” said David Gozal, vice president for health affairs and dean of the Joan C. Edwards School of Medicine at Marshall University.
Study Does Not Prove Cause And Effect
They also noted that the animal experiments used spike protein rather than live SARS-CoV-2 infection, meaning the model did not fully reproduce the complexity of COVID-19 infection.
The findings may help guide future studies on long-term lung monitoring for COVID-19 survivors, especially current and former smokers, and on whether TYMP could become a target for future treatments.
