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Two weeks after her first shot of the Moderna COVID vaccine, Lori Welker went in for a blood test. Then she held her breath.

The Denver mother of two suffers from EGPA — eosinophilic granulomatosis with polyangiitis, a rare inflammatory condition. It’s well controlled now, she says, but for years she received twice-a-year infusions of drugs that tamped down her immune system. One of those medicines, a drug called rituximab, has been linked to vaccine failure in some patients.

Welker knew that her medical condition put her at greater risk for a severe case of COVID. And that understanding had essentially held her captive inside her house. Her kids went to school because she and her husband decided that the family’s risk allotment should be used to give their daughters the most normal life possible.

“But as a result, my husband and I maybe dialed back on our risk and maybe think a little bit more before we go out and do certain things,” she said.

Date nights were practically out of the question. So was visiting family across the country. The COVID vaccines brought optimism that she might be able to return to a more normal life — but only if they worked. It was a lot of hope to put on a single antibody blood test.

Then the results came back: She had hardly produced any protective antibodies after her first vaccine dose. A test after the second shot returned a similar result.

“It was really hard to take when I got the news that it didn’t work,” she said.

Understanding when vaccines fail

For months now, researchers have been trying to understand how many people might be at risk for experiencing vaccine failure. People with suppressed immune systems, like Welker, are obvious candidates — something that’s been long suspected.

But doctors at National Jewish Health recently published a study identifying even more patients who may not fully benefit from the COVID vaccines.

A National Jewish Health researcher studies lung tissue through microscope in this undated file photo. (Provided by National Jewish Health)

The doctors found that, out of a sample of more than 300 patients suffering from chronic illness and being treated at the hospital, about 20% did not have detectable antibodies two weeks or more following vaccination. People on rituximab were especially at risk, but so too were people with congestive heart failure or interstitial lung disease — conditions not previously associated with vaccine failure.

In fact, a significant subset of people suffering from all kinds of different conditions, including asthma and diabetes, failed to produce enough antibodies to be protective. 

One of the National Jewish doctors on the study, Dr. Shu-Yi Liao, called the results “a novel finding” among COVID research.

National Jewish Health pulmonologist Dr. Shu-Yi Liao. (Provided by National Jewish Health)

“Initially people thought, ‘I’m fully vaccinated; I’m safe,’” he said. “But right now that’s not necessarily the truth.”

To the researchers, the study may help explain the high number of breakthrough infections they were seeing in their fully vaccinated patients. Or it might help explain why vaccinated people who die from COVID so often suffer from “comorbidities,” the ominous catch-all medical term for the other medical conditions that complicate an infection.

It may also help their patients better understand the ongoing threat COVID poses to them, as unpleasant as the information may be.

“National Jewish is a place where we want everyone to know their risks,” said Dr. Anthony Gerber, another doctor on the study. “We do testing so we can help people do better and live better.

Piecing together the puzzle

The doctors caution, though, that the study is just one piece of the puzzle.

The research looked at antibody levels, but antibodies are only part of the body’s immune system. Also important are T-cells and components that give the body a longer memory for fighting off an infection. Liao said it’s possible that, even with low antibody levels, people may still get protection from those other parts of the immune system.

Gerber said researchers are now applying for federal funding to look at that bigger picture.

Another part of the puzzle: What is causing patients with some of these chronic conditions not to produce antibodies? For some, medication is an obvious suspect. But not so for others, which means trying to better understand the impact their disease has on their immune systems.

And maybe age plays a role, too. Because National Jewish’s patient population skews older, the patients in the study were older, as well — an average age of 62.

In the meantime, Gerber said policymakers can use the information to help prioritize who gets scarce COVID treatments like monoclonal antibodies or anti-viral pills.

“The message is it’s empowering to know you may not have the protection and then you can be prioritized to get these treatments,” Gerber said.

But it’s also a reminder that, as COVID case counts thankfully begin to fall, the pandemic’s stresses don’t relax for everyone.

Living without antibodies

For Welker, the Denver mom, her high-risk status has made the past two years an especially anxious time.

“There had always been an extra layer of worry throughout COVID,” Welker, who is 46, said.

Though she had tried to give her kids the most normal pandemic life she could, she had also been open with them about her risk. The girls are young — the oldest is only 10 — but Welker said they understood when she explained to them why they needed to be extra careful to wear masks at school activities or why they couldn’t have as many play dates as some of their friends.

When she and her husband went out to eat — which was almost never — they only went to places where they could be seated in their own little igloo pods. Welker kept in regular contact with her doctors, including Dr. Michael Wechsler at National Jewish, who also worked on the antibody study.

The news that she had not produced antibodies after her first vaccine shot was frustrating, Welker said. But it made the news that she still didn’t have protective levels of antibodies after her second shot more expected.

After she received her booster shot in the summer — still not enough antibodies — she began to see a silver lining in the pattern.

“I did consider myself at least really lucky that I knew,” she said.

Trying something new

But she had also begun to research more into why her body was not producing antibodies. She came across studies suggesting that patients who had been on rituximab did begin producing antibodies in response to a COVID vaccine once they were several months past their last dose. She was at that point a year past her last dose.

National Jewish Health pulmonologist Dr. Michael Wechsler. (Provided by National Jewish Health)

So she and Wechsler began talking about an idea that hasn’t been put to widespread use, at least not yet: What if she got a second vaccine booster shot?

After that fourth shot, Welker took another antibody test, then obsessively watched the National Jewish patient portal.

“I was checking it probably about a dozen times a day,” she said.

Until one day she saw her results pop up.

Antibodies.

She had a protective level of antibodies.

“It was really emotional,” she said. “It had been month after month of not knowing if or when it would ever work, just the impact it had on how our family got to interact with the world.”

She quickly called Wechsler to make sure she was reading the results correctly.

“I was thrilled,” he said.

For Welker, the world began to open back up a bit. She made plans to see family members over the holidays. Her family took a trip across the country to visit her brother, the first time they had seen him in two years.

“I wasn’t sure if my antibody levels were that high, but I knew that I had them,” she said. “I felt like I was going to have a better chance of doing OK if I got COVID.”

She also felt an enormous gratitude to Wechsler, who she said “hung in there with me.”

The experience made Wechsler think about a new way of treating high-risk patients.

“We should probably be testing patients for antibodies and identifying who is at risk and giving boosters and or extra boosters to those individuals based on their antibody levels,” he said.

It’s one more sign of how much there still is to learn about the virus and the immune system.

“What we’ve learned from this whole COVID experience is how humbling it is,” he said. “We still need to continue to utilize science to get a better understanding of what’s going on.”

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John Ingold

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