COVID-19 and Its Effects on Cancer Recurrence

In early 2022, as the Omicron variant triggered a significant rise in COVID-19 cases, researchers at James DeGregori’s lab at the University of Colorado Anschutz made an intriguing observation. They found that lab mice with dormant breast cancer cells, once infected with either influenza or SARS-CoV-2, were notably more likely to develop aggressive lung tumors.

Of course, what happens in mice doesn’t always translate to humans. However, when the team looked into healthcare databases, they were taken aback to discover something similar in human populations.

Data from the U.K. Biobank revealed that cancer survivors who contracted COVID in 2020 — a time when the virus was still novel and vaccines were not yet available — were at a significantly higher risk of dying from recurring cancer compared to those who didn’t get infected. This trend was particularly pronounced in the year following their COVID diagnosis.

Additionally, an analysis of breast cancer patients in remission from a separate U.S. database indicated that those who contracted COVID were more likely to develop metastatic lung tumors than their counterparts who were uninfected.

The researchers at the University of Colorado found it challenging to thoroughly assess influenza’s impact since most flu cases don’t make their way into medical records; people often manage mild flu symptoms at home. They also couldn’t explore how the severity of COVID infections linked to cancer recurrences. Still, the novelty of COVID provided them valuable data to investigate the effects of viral inflammation on cancer recurrence, resulting in findings published in the journal Nature last year.

“When cancer returns, it tends to come back aggressively,” DeGregori remarked, suggesting that viral infections might serve as “fuel for the fire.”

Despite the unwelcome emergence of COVID, its widespread nature has significantly enhanced our understanding of how viruses can impact the body well after the initial illness has subsided.

Researchers require substantial data to identify statistically significant patterns. As Dr. Stanley Perlman, a microbiologist at the University of Iowa, noted, a global pandemic where nearly everyone gets infected essentially creates a vast sample size.

The rise in long COVID cases also accelerated research on post-viral syndromes, which include a range of lingering symptoms noted in patients previously afflicted with pneumonia, flu, or other viruses.

Now, with additional post-pandemic data available, scientists are beginning to delve deeper into the complex relationship between COVID and cancer, a disease that often takes longer to manifest.

“This definitely deserves more attention,” stated Dr. Aditya Bardia, who directs Translational Research Integration at the UCLA Health Jonsson Comprehensive Cancer Center. His lab has found associations between COVID and breast cancer recurrence, although that research has yet to go through peer review.

While the evidence remains insufficient to declare COVID an oncogenic virus, several researchers emphasized notable differences between it and known cancer-causing viruses, like HPV linked to cervical cancer and hepatitis B and C associated with liver cancer.

Nonetheless, the pandemic does hint that viral infections might play a role in reactivating dormant cancer cells already present in some patients.

“COVID and influenza don’t directly cause cancer, but if you have latent cancer cells typically kept in check by your immune system, a severe COVID case could reactivate those cancers,” explained Dr. Patrick Moore, a virologist at the University of Pittsburgh.

The sharp rise in metastatic breast cancer cases observed early in the pandemic was primarily attributed to treatment delays caused by restrictions, rather than an actual increase in diagnoses. However, recent findings suggest that something intrinsic to infections, rather than just logistical issues, could be contributing to the recurrence of cancer.

DeGregori’s study indicated that a body’s natural defense mechanism against viral infections involves the release of cytokines — proteins that help coordinate the immune response. Yet, in severe infections, the immune system can sometimes overshoot, producing an excessive amount of these proteins, leading to a dangerous phenomenon known as a cytokine storm.

Initial research during the pandemic found that patients suffering severe COVID who either died or required hospitalization displayed elevated cytokine levels, particularly a protein called interleukin-6 (IL-6). High levels of IL-6 have also been linked to various types of cancer recurrence and metastasis.

DeGregori’s team discovered that when dormant breast cancer cells in mice reactivated post-COVID infection, it correlated with spikes in IL-6. While they couldn’t confirm a similar biological process in humans, the real-life patient data showing a correlation between COVID infection and cancer recurrence supports their hypothesis.

This remains a nuanced topic, with even authors of the research holding diverse interpretations. Dr. Doug Wallace, for instance, suggested an alternate viewpoint, proposing that IL-6’s suppression of mitochondria, the energy-producing parts of cells, might actually drive cancer growth. This dysfunction could also play a significant role in long COVID symptoms.

Wallace noted that many viruses, including SARS-CoV-2, impact mitochondrial function, which might explain both the lingering effects of long COVID and the unexpected cancer recurrences noted in some patients.

Researchers emphasized that this field is still evolving, and no conclusive link has been established between COVID infection and cancer recurrence.

“It’s valid to consider that COVID infection might be one of many potential factors that increase the likelihood of cancer returning, but I lean towards skepticism,” Dr. Eric Winer from Yale Cancer Center commented. “It’s an interesting finding, and we need to explore it further.”

The current evidence highlights the necessity for more research in this area. For individuals with compromised immune systems, taking ongoing precautions against various viral infections remains crucial.

“There’s a compelling reason for those with chronic conditions to avoid severe cases of influenza, COVID, or respiratory syncytial virus, especially since effective vaccines are available,” Moore added.