What is COVID teaching doctors about the relationship between viruses and cancer

At the beginning of 2022, when the Omicron variant began to drive new surgery in cases of COVID-19, researchers from the University of Colorado Anschutz lab of James DeGregori saw something unusual: When lab mice with dormant breast cancer cells were infected with influenza or SARS-CoV-2, the animals were at greater risk of developing pneumonia.

What is true for a mouse is not always true for a human. But when the team examined health care data, they were surprised to find that the same thing seems to be happening in humans.

An analysis of records from the UK Biobank showed that cancer survivors who contracted COVID in 2020 – when the virus was new and there was no vaccine – had a higher risk of dying from recurrent cancer than patients who did not get the virus, especially within a year of being infected with COVID.

An analysis of the American Breast Cancer Center database found that breast cancer patients in remission who contracted COVID were more likely to develop metastatic lung tumors than patients who did not contract the virus.

Researchers at the University of Colorado could not analyze the effects of the flu carefully – most flu infections do not make it to the medical charts, as patients are often out of the usual conditions at home. They were also unable to consider whether the severity of a patient's COVID infection had an effect on cancer recurrence. But the novelty of COVID has given the team the data they need to track the effects of viral inflammation on cancer recurrence. Theirs results were published last year in the journal Nature.

“When [cancer] it comes back, it comes back furiously,” said DeGregori.

As unpredictable as the emergence of COVID, the extent of its spread has greatly deepened scientific understanding of the ways in which viruses can continue to affect the human body long after the initial illness has passed.

Scientists need valuable data to be able to identify statistically significant patterns. In the case of a global pandemic “where all the people are infected, you actually have a population of seven billion people,” said Dr. Stanley Perlman, a microbiologist from the University of Iowa who studies the coronavirus.

The rapid increase in patients suffering from the long-term study of COVID has post-viral syndromes – a complex set of long-lasting symptoms that doctors have long seen in other patients infected with pneumonia, influenza or other viruses.

Now, with years of post-pandemic data being collected, scientists are able to look more closely at the complex relationship between COVID and cancer, a disease that is taking too long to recognize.

“This is something that needs more attention,” said Dr. Aditya Bardia, director of Translational Research Integration at UCLA Health Jonsson Comprehensive Cancer Center. Bardia's lab also saw an association between COVID-19 infection and breast cancer recurrence; that research has not been submitted for peer review.

There is not enough evidence to show that COVID is an oncogenic, or cancer-causing, virus, said two dozen researchers contacted for this article. This virus has important structural differences from known oncogenic viruses such as the human papilloma virus, which is linked to cervical cancer, and hepatitis B and C, which is linked to liver cancer.

But the pandemic has left behind some evidence that viral infections can play a role in reawakening dormant cancer cells that were present in the patient's body before infection.

“Covid and the flu don't cause cancer under them, but if you have cancer and you have dormant cancer cells that are normally controlled by the immune system, getting a severe case of COVID can help reactivate that cancer,” said Dr. Patrick Moore, an epidemiologist at the University of Pittsburgh.

A sharp increase The incidence of metastatic breast cancer in the early years of the epidemic was largely due to delayed care due to the limitations of the epidemic, rather than an actual increase in incidence.

The latest work suggests that “it's not just an epidemic, but it's actually a natural phenomenon of infection” after the association with the development of cancer, said Melanie Ott, director of the Gladstone Institute of Virology and professor of medicine at UC San Francisco.

The effect is not specific to COVID, as DeGregori's Nature paper shows, Ott pointed out. One of the body's natural defense mechanisms against a virus such as COVID or the flu is the release of cytokines, proteins that act as chemical messengers that help coordinate the immune system's response.

But in some cases of severe infection, the immune system can overreact and send an excessive amount of these proteins, a serious and potentially dangerous reaction called a cytokine storm.

Research in the early months of the pandemic showed that patients with severe COVID who died or required hospitalization were more likely to have elevated levels of cytokines, including a specific protein called interleukin-6, or IL-6.

High levels of IL-6 have also been present connected recurrence and metastasis of many types of cancer.

DeGregori's team found that breast cancer cells in mice with their dormant cancer came back after the COVID infection was reactivated due to high levels of IL-6. Their research could not prove that the same biological process occurs in humans, DeGregori said. But the fact that a review of real-life patient data showed a high correlation between COVID-19 infection and cancer recurrence makes him think something is up.

It is not a settled question, even among the authors of the paper. Dr. Doug Wallace, director of the Center for Mitochondrial and Epigenomic Medicine at the Children's Hospital of Philadelphia and co-author of the Nature paper, said he has a “slightly different interpretation” of the data.

IL-6 also inhibits mitochondria, the cell's energy-producing components. Wallace thinks that this suppression of cell energy is actually what promotes the growth of cancer. (Mitochondrial dysfunction is also a the main suspect due to prolonged COVID.)

Some viruses shut down mitochondrial function as well, Wallace said. SARS-CoV-2 seems to be very good at it, which could be the reason the infection leads to a long-lasting COVID-19 illness in some people or an unexpected cancer recurrence in others.

The researchers stressed that this area of ​​study is still in its early days, and there is no direct causal link between the infection of COVID and the return of the cancer.

“It's fair to say that [COVID infection] may be added to the long list of theoretical reasons that the cancer may return, [but] I'm on the skeptical side of things. Prove it to me,” said Dr. Eric Winer, director of the Yale Cancer Center.

The evidence so far suggests that this question deserves more research, the researchers said. If there is any action that should be taken by people with compromised immune systems as a result, it is to continue to take reasonable measures to prevent infections caused by viruses of all kinds.

“There's a big, very compelling reason for those patients with chronic illnesses to avoid getting a bad flu or COVID or respiratory syncytial virus. [virus] – all these diseases for which there are good, safe, effective vaccines,” said Moore.