A new discovery by researchers at Marshall University’s Joan C. Edwards School of Medicine and the Hebrew University of Jerusalem identifies a potential link between COVID-19 infection and increased risk of lung cancer, driven by underlying biological mechanisms in the lungs.
This study Frontiers of immunologyaims to integrate human clinical data with mechanistic studies in animal and cell models to better understand how SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), contributes to long-term lung disease.
Our findings suggest that COVID-19 not only causes acute illness, but also induces biological conditions in the lungs that may contribute to increased cancer risk in the long term. Understanding these pathways is critical as we continue to study the long-term health effects of the virus. ”
Wei Li, Ph.D., Joan C. Edwards Professor of Biomedical Sciences, School of Medicine, and co-corresponding author of this study
This study identified a critical role for thymidine phosphorylase (TYMP), a protein that interacts with the SARS-CoV-2 spike protein and may promote inflammation, fibrosis, and tumor-related pathways in the lungs. The researchers found that this interaction can activate processes associated with cancer growth and alter the immune environment of the lungs in a way that supports tumor formation.
Using a large clinical dataset from the TriNetX research network, the research team also observed higher rates of lung cancer among patients with a history of COVID-19, particularly among current and former smokers. The authors note that additional research is needed to better understand this relationship and its long-term effects.
Cayleigh Wallace of Marshall University and Alex Gileles-Hillel, MD, of Hebrew University and Hadassah Medical Center, served as co-lead authors of the study. Dr. Li and Dr. Hongyue, a professor at Marshall University, served as co-corresponding authors. This research supports a pending NIH R03 grant application led by Yue and David Gozal, MD, MBA, Ph.D. (Hon) of Marshall University is serving as a consultant.
“Through our collaboration with basic and translational scientists and clinicians, we were able to identify the mechanisms underlying the epidemiological evidence linking COVID-19 infection to a potential increased risk of lung cancer,” said Gozal, vice president for health affairs and the Joan C. Edwards Dean of Medicine at Marshall University. “This is exactly the type of research that the School of Medicine aims to expand on in the coming years.”
This finding provides a foundation for future research focused on understanding long-term cancer risk and identifying potential targets for prevention and treatment.
This research was funded by R15HL145573 and R01HL177493 (to WL), support from the West Virginia Clinical and Translational Sciences Institute Pop-up COVID-19 Fund (to WL), support from the National Institute of General Medical Sciences (U54GM104942), the Cancer Biology Pilot Grant Program (to WL), and support from the West Virginia IDeA Network of Biomedical Research Excellence. (WV-INBRE, P20GM103434).
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Marshall University Joan C. Edwards School of Medicine
Reference magazines:
Wallace, C. Others. (2026). Thymidine phosphorylase promotes lung tumor development by the SARS-CoV-2 spike protein. Frontiers of immunology. DOI: 10.3389/fimmu.2026.1798566. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1798566/full
