‘Unusual’ cancers emerged after the pandemic. Doctors ask if COVID is to blame.

ROCK HILL, S.C. - Kashyap Patel looked forward to his team’s Friday lunches. All the doctors from his oncology practice would gather in the open-air courtyard under the shadow of a tall magnolia tree and catch up. The atmosphere tended to the lighthearted and optimistic. But that week, he was distressed.

It was 2021, a year into the coronavirus pandemic, and as he slid into a chair, Patel shared that he’d just seen a patient in his 40s with cholangiocarcinoma, a rare and lethal cancer of the bile ducts that typically strikes people in their 70s and 80s. Initially, there was silence, and then one colleague after another said they’d recently treated patients who had similar diagnoses. Within a year of that meeting, the office had recorded seven such cases.

“I’ve been in practice 23 years and have never seen anything like this,” Patel, CEO of Carolina Blood and Cancer Care Associates, later recalled. Asutosh Gor, another oncologist, agreed: “We were all shaken.”

There was other weirdness, too: multiple patients contending with multiple types of cancer arising almost simultaneously, and more than a dozen new cases of other rare cancers.

Increasingly, Patel was left with an unsettling thought: Could the coronavirus be inflaming the embers of cancer?

The uptick in aggressive, late-stage cancers since the dawn of the pandemic is confirmed by some early national data and a number of large cancer institutions. Many experts have mostly dismissed the trend as an expected consequence of disruptions to health care that began in 2020.

But not everyone.

The idea that some viruses can cause or accelerate cancer is hardly new. Scientists have recognized this possibility since the 1960s, and today, researchers estimate 15 to 20 percent of all cancers worldwide originate from infectious agents such as HPV, Epstein-Barr and hepatitis B.

It will probably be many years before the world has conclusive answers about whether the coronavirus is complicit in the surge of cancer cases, but Patel and other concerned scientists are calling on the U.S. government to make this question a priority knowing it could affect treatment and management of millions of cancer patients for decades to come.

“We are completely under-investigating this virus,” said Douglas C. Wallace, a University of Pennsylvania geneticist and evolutionary biologist. “The effects of repeatedly getting this throughout our lives is going to be much more significant than people are thinking.”

But there is no real world data linking SARS-CoV-2 to cancer, and some scientists remain skeptical.

John T. Schiller, a National Institutes of Health researcher and pioneer in the study of cancer-causing viruses, said pathogens known to cause cancer persist in the body long-term. But the class of respiratory viruses that includes influenza and RSV - a family that counts the coronavirus as a member - infects a patient and then typically goes away instead of lingering and is not believed to cause cancer.

“You can never say never, but that sort of … virus does not suggest being implicated in cancers,” Schiller said.

David Tuveson, director of the Cancer Center at Cold Spring Harbor Laboratory and former president of the American Association for Cancer Research, said there’s no evidence the coronavirus directly transforms cells to make them cancerous. But that may not be the full story.

Tuveson said a number of small and early studies - many of which have been published within the past nine months - suggests that coronavirus infection can induce an inflammatory cascade and other responses that, in theory, could exacerbate the growth of cancer cells.

He has wondered whether it could be more akin to an environmental stressor - like tobacco, alcohol, asbestos or microplastics.

“Covid wrecks the body, and that’s where cancers can start,” Tuveson said, explaining how autopsy studies of people who died of COVID-19 showed prematurely aged tissue.

Even as the first wave of the coronavirus pummeled the United States, public health officials predicted a surge of cancer cases. A Lancet Oncology paper analyzed a national registry showing increases of Stage 4 disease - the most severe - across many cancer types in late 2020. Baptist Health Miami Cancer Institute, UC San Diego Health and other large institutions have released data showing continued increases in late-stage cancers.

Xuesong Han, scientific director of health services research at the American Cancer Society and lead author of the Lancet Oncology study, attributed the jump to people delaying or skipping care because of fears related to the virus or because of economic reasons and also to cultural factors, language barriers and discrimination. But Han acknowledged that biological mechanisms of SARS-CoV-2, the virus that causes COVID-19, could be at play.

“I don’t have the data to support this opinion,” Han said. “But it’s an important question to follow up on.”

‘Hopefully, we’re wrong’

The human body is made up of trillions of cells in a constant state of growth, repair and death. Most of the time, cells with damaged DNA fix themselves, or simply disappear. Sometimes, they start collecting mistakes in their genetic code and rampage out of control into tumors, destroying parts of the body.

Afshin Beheshti is president of the COVID-19 International Research Team, a group of scientists from eclectic backgrounds who got together during the pandemic to consider out-of-the-box of ways to tackle the virus. Beheshti’s background is in cancer biology, and he said that as the science on the virus evolved - including studies showing widespread inflammation following infection, impact on the vascular system and infection in multiple organs vulnerable to cancer stem cell development - he kept thinking “the signals seemed to be related to early cancer changes.”

“It kept nagging on my mind,” he said.

About a year ago Beheshti, a visiting researcher at MIT and Harvard’s Broad Institute, reached out to Patel, who is a past president of the Community Oncology Alliance, a national group of independent cancer specialists, and they hosted a symposium with other scientists that concluded compelling evidence exists suggesting links between the coronavirus and cancer.

“Hopefully, we’re wrong,” Beheshti said. “But everything is, unfortunately, pushing toward that being the case.”

The group’s loosely affiliated members are launching research studies that are trying to piece together the puzzle of coronavirus infection, long COVID and cancer.

Wallace - the University of Pennsylvania scientist considered a father of the field of human mitochondrial genetics, which explores the power plants that fuel human cells - is researching how COVID affects energy production in cells and how that might influence cancer vulnerability.

Separately, biodata experts are sequencing the gene profiles of organs from people who succumbed to COVID and underwent autopsies.

And a University of Colorado team is studying whether COVID reawakens dormant cancer cells in mice. Their provocative findings, according to a preprint report released in April, showed that when mice that were cancer survivors were infected with SARS-CoV-2, dormant cancer cells proliferated in the lungs. They saw similar results with the flu virus.

Ashani Weeraratna, a professor at the Johns Hopkins Bloomberg School of Public Health, said the Colorado study, which she did not participate in, is part of a new field of work that emerged during the past decade that drills into what stimuli can reawaken cancer cells.

She said it is consistent with research highlighting the importance of the immune system in activating cells from dormancy, so it makes sense that “something like influenza or COVID that triggers inflammation could change in the immune microenvironment.” But the results surprised her because “it’s rare the data are so striking.”

Weeraratna said that while she believes the Colorado study’s findings are important, they should be interpreted with caution. Studies in mice often do not translate to human experiences. She said it’s also important to emphasize that the research and other recent papers focusing on COVID and cancer involve acute infection or long COVID; they do not suggest a link between the coronavirus vaccine and cancer - misinformation that some anti-vaccine groups have spread in recent months.

Still, Weeraratna said, there’s an important public health takeaway.

“Mitigating risk of infection may be of particular importance for cancer patients,” Weeraratna said. Based on the study’s findings, measures adopted by vulnerable patients starting in the early days of the pandemic - wearing masks, avoiding crowded places, getting vaccines - become even more important.

Other studies offer telltale clues about the link between viruses and cancer.

Pathologists from the University of Arkansas for Medical Sciences reported in 2021 in the journal Communications Biology that SARS-CoV-2 proteins fueled the replication of a herpesvirus considered one of the major viruses leading to cancer. Other studies have implicated the coronavirus in helping to stimulate dormant breast cancer cells.

A paper published in 2023 in the journal Biochimie explored mechanisms the coronavirus could exploit to aggravate several forms of cancer, including lung, colorectal, pancreatic and oral. Researchers suggested the most likely pathway was through disrupting the body’s ability to suppress tumors, but researchers acknowledged a lack of direct evidence to support the theory.

Wallace believes the dearth of hard data on the coronavirus and cancer reflects policy choices more than scientific challenges.

“I would say most governments don’t want to think about long COVID and much less long COVID and cancer. It cost them so much to deal with COVID. So there is very little funding for the long-term effects of the virus,” he said. “I don’t think that’s a wise choice.”

‘Everyone has it’

From his practice in this Southern town, Patel is conducting his own research into what he has taken to calling “an unusual pattern” of cancers. He is driven by watching patients - especially younger ones - die so quickly.

He’s looking at potential correlations between long-COVID markers and unusual cancers. He has collected data from nearly 300 patients and wants to create a national registry to analyze trends. So far, his office has logged more than 15 patients with multiple cancers, more than 35 patients with rare cancers and more than 15 couples with new cancers since the pandemic began in 2020.

Patel theorizes the effects of coronavirus infections could be cumulative in people infected multiple times. Pandemic-related stress may compound the threat, he said, by exacerbating inflammation.

If a link is established between the virus and cancer, he said, doctors might identify patients at greater risk and implement screenings earlier and even put some patients on anti-inflammatory drugs.

Mammograms and colonoscopies would have done nothing to prevent the illness of one of Patel’s patients, a 78-year-old diagnosed with three cancers - throat, liver and lungs - within a year.

Then there’s Bob and Bonnie Krall, a couple who in a 14-month stretch endured three types of cancer between them, despite neither having a family history or genetic predisposition.

Cancers typically start in one part of the body and spread. It’s rare for discrete cancers to begin in different parts of the body during a short window of time. Patel said the Kralls and the 78-year-old had coronavirus antibodies “through the roof” in their blood although he’s not sure how that relates to cancer, if at all.

Patel met the Kralls in 2022 when Bob was diagnosed with chronic lymphocytic leukemia, a cancer of the blood and bone marrow. During one of her husband’s treatments, Bonnie mentioned she was dealing with her own health issues related to long COVID, including stomach pain. Medications weren’t helping. Patel ran tests and discovered Bonnie had cancer, too. By the time she was scheduled for surgery a few weeks after diagnosis, the malignancy in her abdomen had grown three more centimeters and weighed 8.5 pounds. This year, Bob’s doctors found cancer in his lungs.

Bob’s blood cancer, CLL, is considered rare with only four or five cases in every 100,000 people, but he has been surprised to find four of his neighbors and friends have it, too.

“It’s like a cold. It seems like everyone has it,” said Bob, 73, a flight instructor.

Even before Patel mentioned his research, Bonnie, 74, who used to work part-time as a front desk assistant and lives with her husband in Fort Mill, S.C., had wondered whether their cancers were related to the coronavirus. She was infected shortly before her cancer diagnosis.

“Maybe if we didn’t get COVID …” she started before trailing off. Bob shrugged and finished for her. “Maybe we would have been better? Maybe we would have been worse.”