Vaccine reaction may be mistaken for cancer
Experts advise telling doctor about shot to avoid false alarms
Getting a mammogram or other cancer check soon after a COVID-19 vaccination? Be sure to tell the doctor about the shot to avoid false alarm over a temporary side effect.
That’s the advice from cancer experts and radiologists. Sometimes lymph nodes, especially in the armpit, swell after the vaccinations. It’s a normal reaction by the immune system but one that might be mistaken for cancer if it shows up on a mammogram or other scan.
“We need to get the word out,” said Dr. Melissa Chen, a radiologist at the MD Anderson Cancer Center in Houston who recently had to reassure a frightened patient who sought cancer testing because of an enlarged lymph node.
An expert panel from three cancer centers — MD Anderson, New York’s Memorial Sloan Kettering and Boston’s Dana-Farber — published recommendations in the journal Radiology last week on how to handle scans complicated by the side effect.
The main message: “This should not prevent patients from getting the vaccine,” stressed Chen, one of the coauthors.
Lymph nodes are part of the immune system where infectionfighting white blood cells gather, spots usually too small to feel. But they can swell during illness and after other types of vaccines. And with the anticipated jump in COVID-19 vaccinations, doctors should “prepare to see large volumes” of imaging exams — including chest CTs, PET scans and mammograms — that show swollen lymph nodes, according to similar recommendations in the Journal of the American College of Radiology this week.
The nodes most commonly affected are in the armpit and near the collarbone, on the same side as the vaccination, Chen said.
The Food and Drug Administration
lists the swelling along with other injection-related reactions commonly reported in studies of the Pfizer and Moderna vaccines, although not for the Johnson & Johnson vaccine.
It’s not clear how often it happens. The FDA found 16 percent of participants in the Moderna study reported some underarm swelling after their second dose. But if the lymph nodes are only slightly enlarged, they may show up on a medical scan without people noticing any bumps.
The consumer advice still is evolving. Where experts agree: If you’ve recently been vaccinated, tell the radiologist before any scan. That will help them evaluate if an enlarged lymph node is probably vaccine-related and can simply be monitored, or if it’s worrisome
enough for a biopsy or other test.
And try to schedule an upcoming screening or other cancer-related scan ahead of vaccination if it’s possible without losing your place in the vaccine line, the Radiology panel said.
People with active cancer that’s on one side of the body can choose vaccination on the opposite side to minimize confusion.
Don’t delay any urgent exams, radiologists stress. But there’s some disagreement about non-urgent scans. The Radiology panel said to consider scheduling purely routine screenings six weeks after vaccination. In contrast, recommendations from Massachusetts General Hospital urge handling the side effect with good communication rather than delayed screening.
If messenger-RNA vaccines are the breakout medicine of the pandemic, then the tiny lipid spheres that bring them into people’s cells are the unsung heroes.
The world desperately needs more of both.
Consider BioNTech, which until a year ago purchased only a few grams at a time of lipids to support a drug-development program that most people thought was years away from becoming mainstream. Now it’s tapping big German chemical companies such as Merck and Evonik Industries to vastly scale up production of the materials, a crucial step if it and partner Pfizer are to make good on plans to ship 2 billion doses of their COVID-19 vaccine this year.
“We need kilos and kilos and kilos of that stuff,” said Sierk Poetting, BioNTech’s chief financial officer, citing lipids as one of his most pressing needs.
Producers are benefiting. On Thursday, Merck forecast record earnings this year, pointing to surging demand for the unit that’s making lipids, among other supplies, for vaccine developers.
Lipids catapulted toward the top of the world’s health care priority list because the potent vaccines from Pfizer-BioNTech and Moderna, as well as others still being developed by CureVac and Sanofi, can’t do their job without them. Messenger RNA, the genetic material at the heart of these vaccines, needs a protective shell composed of four different types of the fatty material — collectively called a lipid nanoparticle — so that it can successfully journey from factory to a person’s arm, and then get inside of human cells.
With governments looking to turbocharge production of COVID vaccines, officials are learning that making more lipids isn’t so easy.
“This is an incredibly complex process,” said President Joe Biden, touring a Michigan factory
last month alongside Pfizer CEO Albert Bourla, who vowed to produce more lipids — along with mRNA — at the facility as part of a push to double vaccine supplies. Biden marveled at the close collaboration between machine technicians, chemists and biologists who were “pioneering technologies that less than a year ago were little more than theories and aspirations.”
For Bob Langer, those aspirations stretch back a lot longer. As early as the 1970s, he was trying to prove you can capture and transport big, complex molecules such as DNA and RNA inside tiny particles without destroying them.
“Everybody told me it was impossible,” he recalled during a phone interview. “I got my first nine grants rejected. Couldn’t get a faculty job.”
Turns out it was possible, and Langer wasn’t out of a job for long. Today, the professor has a chemical engineering lab at Massachusetts Institute of Technology
bearing his name, focused on the intersection of biotechnology and materials science. Following decades of development, Langer in 2010 co-founded Moderna, where he’s still on the board. That company — like BioNTech and CureVac — is developing mRNA vaccines for infectious diseases beyond just COVID, along with therapies for cancer and rare illnesses.
“I don’t think people realized just how important the delivery systems are to all kinds of medicines,” Langer said. “If you get more and more complex medicines, like RNA and DNA and things like that, you’ll see more and more work on delivery systems and more and more problems will be solved. Lipid nanoparticles are going to be a big piece of the arsenal.”
The drug delivery field had a watershed moment in 2018, when the Food and Drug Administration approved a new therapy from Alnylam Pharmaceuticals. That drug, Onpattro, treats a rare
genetic disease that causes nerve and heart damage. While it works somewhat differently than mRNA therapies, it’s delivered via lipid nanoparticles. That meant regulators had at least some comfort level with the concept before the pandemic.
Thomas Madden worked for years with Alnylam on developing those pioneering lipids. By the time the approval came, though, he had long since refocused his Vancouver-based company, Acuitas Therapeutics, on what he considered the more promising field of mRNA. He recalls a eureka moment in about 2011, when he read a scientific paper detailing recent progress in the field and concluded companies still needed better tools for delivery. That’s because the body is teeming with enzymes designed to immediately cut up any mRNA found circulating outside of cells.
To prevent that from happening, the mRNA in COVID shots sits inside the shell composed of four lipids. After protecting the mRNA on its journey into a person’s arm, the nanoparticle gets taken up into a cell. There, a positively charged lipid helps the mRNA to escape. Once in the cell’s cytoplasm, the mRNA instructs the cell to produce copies of the coronavirus’s spike protein, inducing the body’s immune system to build up defenses.
Moderna has designed its own charged lipids, while Acuitas licenses its delivery technology to BioNTech and CureVac. Each of these companies was engaged in early clinical trials of mRNA treatments before the pandemic.
When COVID-19 emerged, Madden flew to Germany to talk to regulators and BioNTech officials about how they could most quickly commence clinical trials of mRNA COVID shots. They decided to repurpose the lipid nanoparticle from a rabies vaccine developed by CureVac, since it had already proved effective in people.
“The package doesn’t really care what’s inside,” Madden said. “It’s just going to deliver it.”
In addition to the 2 billion planned doses from Pfizer and BioNTech, Moderna is looking to produce 1 billion shots, while CureVac is targeting another 300 million. These and other companies are also moving fast to develop other mRNA products in their pipelines, adding to the unprecedented demand for lipid nanoparticles.
Major drug- and chemicalmakers have taken notice. In early February, Germany’s Merck agreed to speed up the supply of lipids to BioNTech while Evonik followed suit a week later.
Evonik is repurposing tanks and vessels at two plants in Germany and buying new instruments for the purification process.
“Typically, this process in the pharma industry takes a year or two,” Thomas Riermeier, head of the company’s health care unit, said in a video interview. “What’s required here is to do this more or less in a couple of months.”