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A month after his second dose of the Pfizer COVID-19 vaccine, Robert Montgomery, MD, found his antibody response lacking.

The surgeon and director of the NYU Langone Transplant Institute in New York City is himself a heart transplant recipient -- placing him among the immunocompromised and making him keenly aware that being fully vaccinated didn't necessarily mean he'd be immune to COVID-19.

So Montgomery stepped into uncharted territory when he took a third vaccine dose, crossing over to the Johnson & Johnson shot.

"It now looks like I have a normal response, similar to someone who is not immunocompromised," Montgomery told 麻豆传媒.

He cautioned that he's an "n-of-1" and that many questions need to be addressed before making wide recommendations for immunosuppressed patients, but noted that the potential benefits of a third dose outweighed its unknown risks in his case.

It's estimated that there are about 10 million immunocompromised patients in the U.S. Some 500,000 of them are transplant recipients, while the rest have other autoimmune conditions -- like rheumatoid arthritis, lupus, and multiple sclerosis -- and are taking immunosuppressive drugs.

Rollback of CDC guidance around masking has particularly unnerved this group, as there are significant questions about their level of immune protection even after completing their vaccinations. There's been little guidance as to how they should best protect themselves, other than taking continued precautions.

Staying at home isn't exactly an option for a busy institute director and transplant surgeon, who has to show up to his hospital on a daily basis and interact with multiple patients and colleagues.

Montgomery received his heart transplant in 2018 after multiple sudden cardiac deaths: "There were times when the defibrillator didn't cardiovert me and I needed prolonged CPR," he told 麻豆传媒. "Things were getting very dire."

He had a genetic cardiomyopathy caused by mutations in the , and lost both his father and one of his brothers to the disease.

Around the time of his transplant, he'd recently moved to NYU from Johns Hopkins to build its heart transplant program, incorporating a protocol he'd helped develop involving hepatitis C-positive organs in virus-negative recipients who were treated with novel antivirals. Montgomery was himself a recipient of a hepatitis C-positive heart from a donor who had overdosed.

He'd recuperated and had started to get back to full-time work when New York's COVID surge hit. It took an especially high toll on his transplant patients, with a mortality rate of about 25%, Montgomery said, noting that this rate has since improved.

Since no immunosuppressed patients were included in the vaccine trials, there was little evidence to develop a vaccination strategy for this group. Montgomery first checked his antibodies 2 weeks after his first Pfizer dose -- and they were non-existent.

"I emailed Dorry, 'Houston, we have a problem,'" Montgomery said, referencing Dorry Segev, MD, PhD, of Johns Hopkins, who has been studying vaccine response in transplant recipients and published related in JAMA. Montgomery is a participant in that study.

A month after his second dose, Montgomery saw a minimal antibody response, but upon further investigation still had no neutralizing antibodies at all -- the important antibodies that could suppress COVID infection. He had a poor B-cell response, as well. He also measured T-cell response but said it wasn't clear what that meant about protection at the time, so his team concluded that he wasn't protected.

That's why he opted for a third dose with the J&J vaccine.

He subsequently turned up a very robust antibody and neutralizing antibody response and a normal B-cell response: "Across the board, it was all what you'd see in a normal person," he said.

The anecdote raises many questions that preclude this from being recommended widely to immunocompromised patients. For instance, are the results due to crossover from an mRNA vaccine to an adenoviral vector vaccine? Or would a third dose of the mRNA have produced a similar response?

Also, the science of correlating serum antibody and cellular immunity levels with actual protection from infection, illness, and severe disease and death isn't yet established, though suggested that neutralizing antibody levels are highly predictive of immunity to the virus.

Still, the that people shouldn't pursue antibody tests to tell them whether they're protected against COVID-19, especially after vaccination -- notably because not all commercially available antibody tests measure antibodies to the spike protein. Some, for instance, measure response to the nucleocapsid protein.

Questions about the value of T-cell testing in this population are also unanswered. T-cell testing is generally more difficult to do than antibody testing, although a commercial test is now available. It's just not clear what a patient could do with the information of a positive T-cell test, Montgomery said: "If antibody tests are negative, but T cells have a good showing, does that mean you're protected enough?"

Another question, though potentially less likely, is whether the response was due solely to the Johnson & Johnson adenoviral vector vaccine, which Montgomery said theoretically could lead to stronger immunostimulation.

Finally, it's not clear how long Montgomery's robust response will last. "Is my response going to be more short-lived than a normal person?" he asked. "These are all critical questions."

Montgomery acknowledged taking on the unknown risks of receiving a third dose. That's not necessarily something an immunocompromised patient who can stay home and protect themselves through mechanisms like masking and social distancing would be willing to take on.

Even though Montgomery's family, including two teenage boys, are fully vaccinated, he felt taking the risk was worth it, given his interactions with other transplant patients.

"It's a tough moment right now for transplant patients because there's no clear pathway forward," he said. "We really need a study."

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