For Jennifer Woda, two doses of the Moderna Inc. vaccine were not enough protection against the Covid-19 virus. Over a month later, she got a third and fourth dose, this time with the Pfizer Inc.-BioNTech SE vaccine.
An opera singer who teaches music to kids, Woda received a kidney transplant in September 2019, one of about 160,000 transplants that have occurred in the U.S. since 2017. Emerging research is now showing that these patients, who suppress their immune system with drugs so their bodies don’t reject donated organs, are dramatically less likely to develop protective antibodies using the authorized vaccine dosage.
That’s spurring some recipients to get extra shots as worries mount over the end of pandemic restrictions and as U.S. vaccine supply outpaces demand. They went to pharmacies and clinics to get their shot on their own without doctor’s notes. Some weren’t asked questions about their vaccination history, and some explained their situation and still got the shot.
“I’m willing to be a guinea pig for my sake, and for everybody’s sake.” Woda said by telephone.
Recent studies by Johns Hopkins University researchers found that just 17% of organ recipients developed detectable antibodies after the first dose of an mRNA vaccine while 54% developed them after a second dose. That compares with 100% in early-stage trials on the vaccines. Even the transplant recipients who did have antibodies had generally lower levels than people with healthy immune systems.
Woda isn’t alone in her actions, though she went a step further than many others. The Johns Hopkins researchers are now following numerous transplant recipients who chose to get a third dose after talking with their doctors. While the research is under review, the findings are encouraging, said Dorry Segev, one of the researchers and a professor of surgery and epidemiology at Johns Hopkins.
Meanwhile, transplant patients are anxiously awaiting more information. While they’re used to taking precautions to avoid getting sick, the fact that the coronavirus is airborne and they now can’t tell which unmasked person is or isn’t vaccinated makes them especially fearful.
“We want to resume our life,” said Janet Handal, a kidney transplant recipient who got a Johnson & Johnson shot more than two months after receiving Moderna’s two-shot regimen. “We want to be able to be out in the world and interact with people as we did before -- travel, go to work, go to dinner, go to the kids’ soccer matches.”
Caution Urged
Segev, though, urges caution. He’s seen a higher rate of so-called breakthrough infections among transplant recipients who have been vaccinated compared with the broader population, as well a higher rate of those patients being hospitalized.
“Now is not the time for immunosuppressed people to celebrate the vaccine,” Segev said in an interview. “Now is the time to get the vaccine and we will learn over the next few months how much they can celebrate.”
Segev said his team is working with the Food and Drug Administration and National Institutes of Health to try to launch a clinical trial studying a third dose for transplant patients. The FDA said it would need data to evaluate a dosing regimen outside the current vaccine authorizations.
The Centers for Disease Control and Prevention said the need for and timing of booster doses have not been established, and the safety and efficacy of a mixed-product series have not been evaluated. As a result. people are not recommended to receive more than one vaccine regimen at this time.
Other Countries
Other countries are further along. A clinical trial studying third doses of the Moderna vaccine for transplant patients has begun in Canada, and French health officials have already recommended that severely immunocompromised people get third doses.
Woda, who lives in Cleveland Heights, Ohio, and has sung extensively in the Northeast Ohio area, said that after she received her kidney transplant she began taking high doses of immunosuppressants to make sure the organ wasn’t rejected.
That meant she had to put her performances and in-person teaching with children on hold to prevent getting sick from other people. Then the pandemic hit and she had to hold back even longer.
“When the vaccines finally came, I was like, ‘yes, yes!’” Woda said. “I’ve been starting to imagine, ‘OK once I get this vaccine, I can probably teach again, and then maybe I can think about auditioning again.’”
But those thoughts abruptly ended after Woda joined the Johns Hopkins study conducted by Segev’s team that looked at the response of transplant recipients to the messenger RNA vaccines. That’s when she learned that her body failed to develop antibodies after two doses of the Moderna vaccine.
She then turned to the Pfizer shot, taking the full two-dose regimen.
‘High Chance’
The Johns Hopkins studies were published in the Journal of the American Medical Association in March and May. The first looked at antibody development after a single dose in more than 400 transplant recipients. The second look at the results after a second dose in more than 600 patients. Other patients also began thinking about what to do next as they learned of their results.
The concept of transplant recipients receiving additional or higher doses is not new, Segev said. In his study, an increase in the share of patients who developed antibodies after the second shot compared with the first “implies to me that there is a high chance we will see a continued increase with three doses.”
Additionally, Segev said, the antibody tests used do not show the entire immune response. The test results are correlated to the amount of neutralizing antibodies that someone develops, but does not show cellular immune responses or how long immunity lasts.
His team is now looking at deeper immunology of people who chose to get a third dose.
Transplant Doctor
Robert Montgomery, a transplant doctor at NYU Langone in New York who received a heart transplant in 2018, was likely one of the earliest transplant recipients to take an additional dose.
After becoming fully vaccinated in January with the Pfizer vaccine, he found he had no antibodies and almost no cellular immune response, he said. He talked with other doctors and weighed his risk of Covid exposure as a health-care worker.
Then, two months after his last Pfizer dose, he decided to take the Johnson & Johnson vaccine, the shot available at the time. His response afterward looked similar to that of someone with a healthy immune system, he said.
He doesn’t currently recommend patients get an additional dose since not enough is known about the safety, he said. But many other transplant recipients heard about his story and took heed.
‘Be Like Bob’
One of those was Handal, who communicated with him as she learned of her response to the Moderna regimen. “I knew what Dr. Montgomery’s response was and what my limited response was so far and I said, ‘I want to be like Bob,’” Handal said in an interview.
Other transplant patients got different combinations of vaccine, and Woda went even further and got four doses.
Stephen Thomas, coordinating principal investigator for Pfizer’s late-stage vaccine trial, said if an immunosuppressed patient is shown not to have an effective response to the vaccine, then it’s reasonable for a health-care provider to discuss the risks and benefits of a booster dose with them, knowing that’s outside the current authorization for the vaccines.
He theoretically doesn’t see a safety concern with people getting a third shot of the original vaccine they took at least several weeks after their initial regimen, but he feels less comfortable with the idea of mixing vaccines as there’s less data on that.
And if someone isn’t responding to a third dose, then it’s unlikely a fourth or fifth shot will be of value and additional shots could expose the patient to risk, he said.
Soon Clear
Segev said it could soon become clear who isn’t likely to respond to a third dose and may need an even more aggressive approach, such as adjusting their immunosuppressants. However, he said, that could be dangerous for transplant patients in particular, since changes in medication risk organ rejection.
Still, transplant patients remain hopeful they’ll see action soon.
Beth Trudeau, an elementary school teacher who got a liver transplant in 1998, said she’s worried about the fall, when she’ll have to return to in-person teaching, and her students likely won’t have access to a vaccine yet.
Her doctors didn’t recommend she take a third dose at this time, so she doesn’t feel comfortable getting one. But she’s known about other patients getting extra doses after talking with their doctors.
“That’s kind of the irritating part of it -- it’s like OK, why is it OK for some and not others?” she said, “Why can’t there be some sort of universal decision on this?"
https://www.bloomberg.com/news/articles/2021-06-01/transplant-patients-bypass-rules-on-shots-in-push-to-beat-covid
