COVID-19 and Flu Could Reactivate Dormant Lung Cancer Cells

Respiratory viruses are capable of triggering the growth of dormant cancer cells that have metastasized to the lungs from other body areas. Infectious diseases, such as influenza, can instigate an inflammatory response that aids the immune system in combating pathogens, yet they may also adversely influence cancer progression.

Cancer fatalities frequently result from tumor cells migrating from their primary sites. These cells may remain dormant in new locations for extended periods—potentially years or decades—before forming detectable tumors.

While it is uncertain if these cells will eventually proliferate, previous studies have suggested that once cancer cells infiltrate the lungs, inflammation induced by respiratory virus infections might play a significant role. “Nevertheless, no comprehensive research has been conducted to establish a clear cause-and-effect relationship,” notes James DeGregori from the University of Colorado.

To address this research gap, DeGregori and his team employed genetically modified mice to develop tumors in their mammary glands. By two months of age, each mouse had developed a mammary tumor and fewer than ten dormant cancer cells in their lungs.

Subsequently, the researchers infected half of the mice with the H1N1 influenza strain, commonly referred to as swine flu, causing illness for approximately two weeks. During the nine days following the infection, the number of lung cancer cells surged by 100-fold, whereas uninfected mice exhibited minimal changes.

In complementary experiments, the team discovered that the SARS-CoV-2 virus, responsible for COVID-19, led to a tenfold increase in cancer cell numbers in the mice’s lungs, again with no significant alterations in uninfected counterparts.

The researchers hypothesized that this expansion occurred due to viral infections elevating the levels of inflammatory molecules known as IL-6.

To investigate this hypothesis, they conducted further experiments with genetically modified mice deficient in IL-6 and found significantly fewer lung cancer cells compared to typical mice with normal IL-6 levels.

Another experiment suggested that IL-6 seemed to rejuvenate dormant cancer cells that had already migrated to the lungs instead of promoting the dissemination of these cells from the breasts.

However, IL-6 levels wane when the infection subsides. At this juncture, the researchers observed that cancer cells in the mouse lungs had ceased to proliferate but had acquired alterations in gene expression typically associated with tumor metastasis, according to DeGregori.

These findings suggest a potential impact on individuals with undetected levels of cancer cells in the lungs who are believed to be in remission, as stated by Anne Zeuner at the National Institutes of Health in Rome, Italy.

To determine the relevance of these findings to humans, researchers analyzed health records from 36,800 women in the U.S. diagnosed with breast cancer before the COVID-19 pandemic, who were thought to be non-metastatic.

Women who tested positive during the initial three years of the outbreak were significantly more likely to receive a diagnosis of secondary lung cancer in that timeframe. However, some women may have avoided testing due to asymptomatic infections, while others might not have sought tests, thereby complicating the validation of this finding, notes DeGregori.

Further research is necessary to corroborate these findings and explore the interactions between various respiratory viruses and cancer types, according to Zeuner. “Individual factors are likely to significantly influence the relationship between respiratory infections and cancer recurrence,” she adds.

The research focused solely on swine flu and SARS-CoV-2, but DeGregori expresses hope that a spectrum of viruses will exhibit similar behaviors, as many are known to elevate IL-6 levels. He also underscores the importance of vaccination, stating, “As a cancer survivor, I would ensure I am protected against common respiratory viruses like influenza and COVID-19,” remarks DeGregori.