A small study offers the first hint that an extra dose of COVID-19 vaccines just might give some organ transplant recipients a needed boost in protection.
Even as most vaccinated people celebrate a return to near normalcy, millions who take immune-suppressing medicines because of transplants, cancer or other disorders remain in limbo – uncertain how protected they really are. It’s simply harder for vaccines to rev up a weak immune system.
Monday’s study tracked just 30 transplant patients but it’s an important step toward learning if booster doses could help.
It didn’t help everybody. But of the 24 patients who appeared to have no protection after the routine two vaccinations, eight of them – a third – developed some virus-fighting antibodies after an extra shot, researchers from Johns Hopkins University reported in Annals of Internal Medicine. And six others who’d had only minimal antibodies all got a big boost from the third dose.
“It’s very encouraging,” said Dr. Dorry Segev, a Hopkins transplant surgeon who helped lead the research. “Just because you’re fully negative after two doses doesn’t mean that there’s no hope.”
Next up: Working with the National Institutes of Health, Segev’s team hopes to begin a more rigorous test of a third vaccination in 200 transplant recipients this summer.
For transplant patients, powerful immune-suppressing drugs prevent rejection of their new organs but also leave them extremely vulnerable to the coronavirus. They were excluded from initial testing of the COVID-19 vaccines, but doctors urge that they get vaccinated in hopes of at least some protection.
Some do benefit. The Hopkins team recently tested more than 650 transplant recipients and found about 54% harbored virus-fighting antibodies after two doses of the Pfizer or Moderna vaccines – although generally less than in otherwise healthy vaccinated people.
It’s not just a concern after organ transplants. One study of patients with rheumatoid arthritis, lupus and other autoimmune disorders found 85% developed antibodies, said Dr. Alfred Kim of Washington University in St. Louis.
But those who used particular kinds of immune-suppressing drugs produced dramatically lower levels that are a cause for concern.
“We tell our patients to act like the vaccine is not going to work as well as it does for their family and friends,” said Kim, who would like to test a third dose in autoimmune patients, too. “This is very frustrating news to them.”
Doctors sometimes give extra doses of other vaccines, such as the hepatitis B shot, to people with weak immune systems.
And guidelines issued in France recommend a third COVID-19 shot for certain severely immune-suppressed people, including transplant recipients, Segev noted.
The U.S. hasn’t authorized extra COVID-19 vaccinations. But around the country, a growing number of immune-compromised patients are seeking third doses on their own – the people Hopkins sought to test.
In San Francisco, Gillian Ladd agreed to blood tests before and after an extra dose. The recipient of a kidney and pancreas transplant, Ladd, 48, was terrified to leave her house after learning she had no measurable antibodies despite two Pfizer shots.
With the additional dose, “I had gotten what I needed in order to survive,” Ladd said, but she’s still is sticking with masks and other precautions.
“I am being as careful as I possibly can while acknowledging that I’m coming back into the world of the living,” she said.
Further research is needed to tell if a third dose really helps, who’s the best candidate and if there are brand differences—plus whether the extra immune stimulation could increase the risk of organ rejection.
But Segev cautions boosters aren’t the only possibility. In addition to antibodies, vaccinations normally spur other protections such as T cells that can fend off severe illness. He and several other research groups are testing whether immune-compromised patients get that benefit.
For now, “the best way to protect these people is for others to get vaccinated” so they’re less likely to get exposed to the coronavirus, stressed Washington University’s Kim.
Vaccines in solid-organ transplant recipients
Transplant recipients were excluded from recent SARS-CoV-2 vaccine trials, so neither efficacy, durability, nor safety are known in this patient sub-population. However, as a transplant community, we have extensive experience with vaccine administration in stable transplant recipients, such as the influenza vaccine, although live attenuated virus vaccines are generally contraindicated because of the theoretical risk of disseminated infection.10 , 11
The potential contraindication of live attenuated vaccines is not pertinent to SARS-CoV-2 as there are currently no SARS-CoV-2 vaccine platforms employing attenuated live virus approved for use or in Phase 3 trials; however, if they are developed and approved, they may be a valid approach for some non-immunocompromised pre-transplant candidates who are stable on the waitlist.
Other concerns regarding the SARS-CoV-2 vaccines include lack of long-term safety data, potential reduction in efficacy in immunocompromised patients, unknown durability of the immune response, and potential for vaccine-associated allograft rejection. However, experience with the influenza vaccine and adjuvanted recombinant zoster vaccine can be extrapolated to the COVID-19 vaccine.
First, unanticipated vaccine-associated adverse events to the allograft have not borne out, and vaccines are successfully administered to stable transplant recipients.11 , 12 Second, neither the influenza vaccine nor the adjuvanted recombinant zoster vaccine has been associated with allograft rejection.11 , 12 Finally, although the influenza vaccine may offer sub-optimal immunogenicity (improved with high-dose administration), the adjuvanted recombinant zoster vaccine in kidney transplant recipients demonstrates an adequate immune response and a lack of significant adverse events, including rejection.13 , 14
The novelty of the recently approved mRNA SARS-CoV-2 vaccines has prompted anxiety and misinformation fueled by social media. Use of synthetic mRNA for vaccines is new lipid nanoparticles transport mRNA into cells, enabling translation by human cellular ribosomes into SARS-CoV-212 spike proteins.
However, concern for genetic manipulation is unwarranted: the mRNA is non-replicating, fails to integrate into the human genome, and is degraded after translation. Concerns for viral vector vaccines have focused on a runaway viral infection, especially when the host is immunocompromised.
These concerns also have no scientific basis: the current adenoviral vaccines contain a non-replicating virus; this platform has been used for decades for gene therapy of rare diseases and cancer, although use for vaccination is newly approved. Other vaccines currently under investigation include inactivated virus and protein subunit vaccines; these vaccine platforms have been used in transplant recipients for other infections, including hepatitis A and B viruses, pertussis, and human papilloma virus.11
As transplant clinicians, we should appropriately educate our patients regarding the significant vaccine-related benefits based on the scientific mechanisms and clinical trial findings rather than leave them to interpret the often questionable information on social media. Vaccine acceptance can be maximized by providing accessible educational material for patients and their families, virtual seminars, and one-on-one conversations in which specific fears and questions can be discussed.
The time is now
Although transplant recipients have yet to be studied in SARS-CoV-2 vaccine Phase 3 trials, the benefits in non-transplant recipients are clear, as are the risks our transplant recipients face from COVID-19. In a recent analysis, transplant recipients with COVID-19 had a 30% increased risk of death or mechanical ventilation compared with matched controls.15
The emerging studies on SARS-CoV-2 vaccines indicate that they are safe and effective, and our experience with prior vaccines in stable transplant recipients suggests that the COVID-19 vaccines will also be safe and effective in transplant recipients. Of course, we need to enroll transplant recipients in observational studies, registries, and clinical trials to assess both vaccine immunogenicity, including durability of humoral and cell-mediated immunologic response, and vaccine side effects, including rejection and allosensitization.
In addition, what we learn now will help us navigate the next global infectious threat. Until this information becomes available, we believe that the SARS-CoV-2 vaccines provide potential benefit and minimal risk to stable transplant recipients, particularly when this pandemic is surging in many parts of the globe.
William Osler once said, “Medicine is a science of uncertainty and an art of probability,” and we must accept the uncertainty as we weigh the probabilities of SARS-CoV-2 infection and the vaccine. Our transplant recipients are far more likely to suffer a severe outcome from COVID-19 than from the vaccine. Therefore, as clinicians who strive to optimize the health and wellness of our patients, we believe SARS-CoV-2 vaccination is essential and strongly support and encourage vaccination of our transplanted recipients.
reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834006/
More information: Annals of Internal Medicine (2021). https://www.acpjournals.org/doi/10.7326/L21-0282