Researchers from the University of Colorado Anschutz Medical Campus, Montefiore Einstein Comprehensive Cancer Center (MECCC), and Utrecht University have reported evidence that respiratory viruses, including COVID-19 and influenza, can activate dormant breast cancer cells in the lungs. The study, published in Nature, was conducted using mouse models and supported by analysis of human data.
Julio Aguirre-Ghiso, Ph.D., co-leader of the study and director of MECCC’s Cancer Dormancy Institute at Albert Einstein College of Medicine, commented: “Our findings indicate that individuals with a history of cancer may benefit from taking precautions against respiratory viruses, such as vaccination when available, and discussing any concerns with their healthcare providers.”
The research was led by James DeGregori, Ph.D., senior author and deputy director of CU Cancer Center. Mercedes Rincon, Ph.D., from CU Anschutz, and Roel Vermeulen, Ph.D., from Utrecht University and Imperial College London also served as co-leaders. Dr. DeGregori stated: “This complex and multidisciplinary study truly took a village.”
Previous evidence had suggested inflammation might awaken disseminated cancer cells (DCCs) that are dormant in distant organs after leaving a primary tumor. Dr. Aguirre-Ghiso noted: “During the COVID-19 pandemic, anecdotal reports suggested a possible increase in cancer death rates, bolstering the idea that severe inflammation might contribute to arousing dormant DCCs,” adding his role as leader of MECCC’s Tumor Microenvironment and Metastasis Research Program.
In experiments on mice with dormant DCCs in their lungs—a scenario mirroring key aspects of human disease—the researchers exposed subjects to SARS-CoV-2 or influenza virus. Both infections triggered reactivation of these cells within days, resulting in metastatic lesions appearing within two weeks. Dr. DeGregori explained: “Dormant cancer cells are like the embers left in an abandoned campfire, and respiratory viruses are like a strong wind that reignites the flames.”
Molecular studies showed interleukin-6 (IL-6), an immune protein released during infection or injury, was responsible for this effect. Dr. Aguirre-Ghiso said: “The identification of IL-6 as a key mediator in arousing DCCs from dormancy suggests that using IL-6 inhibitors or other targeted immunotherapies might prevent or lessen the resurgence of metastasis following viral infection.”
To assess risks for humans, researchers analyzed large databases during the COVID-19 pandemic. Using UK Biobank data—a resource tracking over 500,000 people—Utrecht University and Imperial College London scientists studied whether COVID-19 increased cancer-related mortality among survivors diagnosed at least five years prior to the pandemic. After excluding deaths directly due to COVID-19 infection itself, those testing positive for COVID-19 nearly doubled their risk of dying from cancer compared to matched controls who tested negative.
Dr. Vermeulen remarked: “The effect was most pronounced in the first year after infection.” This rapid progression echoed results seen in animal studies.
A second analysis used U.S.-based Flatiron Health data to compare outcomes for female breast cancer patients who did or did not contract COVID-19 while under care at 280 clinics nationwide; 36,216 were negative while 532 tested positive over about 52 months’ follow-up time. The group infected with COVID-19 had almost 50% higher odds of developing lung metastases than those who remained uninfected.
Dr. Vermeulen noted: “Our findings suggest that cancer survivors may be at increased risk of metastatic relapse after common respiratory viral infections,” emphasizing that their study covered periods before vaccines were widely available.
Looking ahead, Dr. DeGregori said: “By understanding underlying mechanisms, we will work hard to develop interventions that can limit the risk of metastatic progression in cancer survivors who experience respiratory viral infections. We also plan to extend our analyses, both in animal models and through mining of clinical data, to other cancer types and other sites of metastatic disease… Respiratory viral infections are forever a part of our lives so we need to understand the longer-term consequences of these infections.”
