Laura Burns was thrilled when she got her second dose of the COVID-19 vaccine three months ago. The 71-year-old thought that with vaccination, she might finally be closer to being able to see her family in Europe again.
"I have not seen them now for two years, and that's including my stepdaughter. It's very, very ... that's hard," says Burns, who lives in Austin, Texas.
But when researchers at Johns Hopkins analyzed her blood, they couldn't detect any antibodies to the coronavirus. "I had no response whatsoever," she says. So she asked the doctors, " 'Does this mean I have no protection?' And the answer I got was, 'It means you may have no protection. You should operate on that assumption.' "
And she's not the only one.
For most people, COVID-19 vaccines promise a return to something akin to normal life. But for the hundreds of thousands of people in the U.S. who have a transplanted organ, it's a different story. That includes Burns, who got a double lung transplant nearly five years ago. New research published this week in the medical journal JAMA suggests many transplant recipients may not get protection from vaccination, even after two doses.
"Forty-six percent of transplant patients have had no evidence whatsoever that they had an antibody response to the vaccine" after two doses, Dr. Dorry Segev says. He's a transplant surgeon at Johns Hopkins and one of the authors of the study, which looked at the antibody response after full vaccination with the Moderna and Pfizer shots in more than 650 transplant recipients, including Burns.
"One of the things that we're really trying to emphasize to the transplant population is, vaccination does not mean immunity," Segev says.
And even in transplant patients who did generate an antibody response from the vaccine, he says, "it is less robust than in people with competent immune systems."
Avoiding organ rejection requires lifelong immune suppression
Valen Keefer has shown at least some antibody response and considers herself lucky. At 38, she's received not one but two organ transplants — a kidney transplant at 19, and a second transplant three years ago, when her liver started failing. As is almost always the case with transplants, Keefer is on a lifelong regimen of strong daily doses of immunosuppressive drugs to keep her body from rejecting those organs.
Just this week, Keefer received test results that showed her body has produced antibodies in response to both the first and second dose of the COVID-19 vaccine — though her response was weaker than that seen in people with normal immune systems.
"I'm grateful," she says. "I almost felt proud of my body. If I had two different transplants and my body could still produce antibodies, there is hope for others."
But Keefer is also confused about what the results mean in terms of her ability to navigate the world safely. "I think it's really hard to integrate back into some kind of normalcy," she says. "Transplant recipients like me, we're not sure what to do."
What about other immunocompromised patients?
The vaccine development trials did not include transplant recipients, so researchers are now trying to fill in the blanks — and not just for those patients. Millions of people in the U.S. are immunocompromised. Some have medical conditions that suppress their immune systems. Others have conditions such as rheumatoid arthritis or inflammatory bowel disease that require them to be on medications that may mute their immune response to COVID-19 vaccines in varying ways, too.
For instance, Segev's study found transplant recipients will have a reduced response to vaccination if they take a class of drugs called antimetabolites. (That drug class includes mycophenolate, azathioprine and methotrexate, a medication also prescribed to some patients who have rheumatoid arthritis or lupus.) These drugs block activity in B cells — the immune system's antibody factories.
Other studies have shown a reduced antibody response in patients who take Rituximab, a monoclonal antibody treatment that also targets B cells and is used to treat some cancers and autoimmune disorders.
"We know for a fact that drugs like this wipe out your B cells. ... And so it's not going to be surprising that these groups of patients aren't going to respond to the vaccines," says Ghady Haidar, a transplant infectious disease doctor at the University of Pittsburgh Medical Center.
However, he says, there are so many immunosuppressive drugs in use that, without more research, it's too soon to know which doses of which drugs in what combination might seriously blunt the benefits of COVID-19 vaccination.
The medical condition makes a difference, too. For example, Segev's research has found that the COVID-19 vaccine was more likely to work in patients with rheumatic and musculoskeletal diseases than in organ transplant recipients. And while Haidar's team failed to detect antibodies in 46% of patients with blood cancers after two doses of either the Pfizer or Moderna vaccines, researchers in the U.K. have found that patients with solid tumor cancers respond well after the second dose.
All this may leave immunocompromised individuals desperate to know whether they responded to the COVID-19 jabs they recently received, but Haidar and other experts NPR spoke with don't recommend that they seek out antibody tests on their own — in part because the commercial tests available may not measure the right thing, and also because scientists have still not established what level of antibodies are required for full protection.
Booster shots down the road?
Right now, Haidar says, the best advice he can give his patients is to get vaccinated — but keep living cautiously, adhering to the same masking and physical distancing precautions they've been following throughout the pandemic.
And just assume you're not protected, he advises. "I know it sounds lame, but this is all that can be offered now."
He hopes and expects that advice eventually to change as research now underway explores which factors influence the way vaccines work in immunocompromised patients. For instance, scientists are starting to explore whether the COVID-19 vaccine may be generating a response in other parts of the immune system — such as among T cells — that they just haven't detected yet.
"It's certainly possible that even if you have no antibodies, that your immune system is ready and waiting to respond whenever the SARS-CoV-2 virus comes, or that there might actually be an active immune response that's sort of hidden in the background," says Dr. Elad Sharon, an immunotherapy researcher at the National Cancer Institute.
It's also possible that giving immunocompromised patients a third dose of a vaccine — essentially a booster shot — will elicit a better antibody response. Last month, health officials in France recommended that severely immunocompromised patients receive a third dose of the Pfizer or Moderna vaccines. The vaccines aren't currently authorized for that use in the U.S., but Sharon says he eventually hopes to test that. In the meantime, some immunocompromised patients are already seeking out third shots on their own. That includes Burns.
"I just called up and explained the situation and the pharmacist gave me the Johnson & Johnson" vaccine," Burns says. She'd been vaccinated earlier with the Moderna vaccine but switched to J&J for the third dose in hopes of eliciting an antibody response by mixing and matching vaccines, a strategy embraced by some health agencies in Europe. "Knock on wood that it's going to work," Burns says. As part of the Johns Hopkins study, she'll get her levels of antibodies against the coronavirus tested again next week.
For now, though, she is still extra careful to keep from getting exposed to the coronavirus — she remains mostly homebound these days. Aside from members of her household, Burns only visits with people over Zoom. When she does venture out for a quick trip to the grocery store, she'll double-mask. Masking is a familiar habit from the early months after her transplant in 2016, when the risk of organ rejection was highest, so she was on higher doses of immunosuppressive drugs. In more recent years, until the pandemic struck, she'd been able to live a much more active life, full of dinners out, indoor exercise classes and travel.
For now, scientists say the best chance that Burns and others have to be protected from getting COVID-19 is for everyone else around them to get vaccinated.
"It's yet another reason for everybody in the United States to go and get vaccinated," Segev says, "because your body can produce an immune response to protect you and all of those around you — so that people whose bodies cannot produce an immune response can somehow be protected."
Keefer calls that responsibility to the community "the burden of good health."
"If you're lucky to be completely healthy," she says, "the burden of that is to step up and help protect yourself and others and get the vaccine. And that's all you have to do."