Vaccines Won’t Protect Millions of Patients With Crippled Immune Systems

Dr. Howard Wollowitz has been at the monastery for the most part at his Mamaroneck, NY home for more than a year

As chief of emergency medicine at Montefiore Medical Center in the Bronx, 63-year-old Dr. Wollowitz eager to treat patients when the coronavirus raged in town last spring. However, cancer treatment in 2019 had wiped out his immune cells, leaving him defenseless against the virus. Instead, he arranged for his employees to be managed through Zoom.

A year later, people return to Dr. Wollowitz’s life returned to a semblance of normalcy. His wife, dancer and choreographer, is preparing to work for the Austrian National Ballet Company. His vaccinated friends meet, but he only sees them when the weather is nice enough to sit in his back yard. “I spend very little time in public areas,” he said.

Dr. Wollowitz, like his friends, was vaccinated in January. But he wasn’t producing antibodies in response – and he hadn’t expected it either. He is one of millions of Americans with weakened immune systems whose bodies cannot learn to use immune fighters against the virus.

Some immunocompromised people were born with missing or faulty immune systems, while others, like Dr. Wollowitz, have illnesses or have received therapies that wipe out their immune defenses. Many of them make little to no antibodies in response to a vaccine or infection, which makes them susceptible to the virus. If infected, they can suffer from prolonged illness, with a death rate of up to 55 percent.

Most people who have lived with immunodeficiency for a long time are probably aware of their vulnerability. However, others have no idea that drugs could put them at risk.

“They’ll be walking around outside thinking they’re protected – but maybe not,” said Dr. Lee Greenberger, scientific director of the Leukemia Lymphoma Society, which funds research into blood cancer.

The only recourse for these patients – other than housing until the virus is withdrawn – may be to regularly infuse monoclonal antibodies, which are mass-produced copies of antibodies obtained from people who have contracted Covid-19 have recovered. The Food and Drug Administration has approved several monoclonal antibody treatments for Covid-19, but some are now also being tested to prevent infection.

Convalescent plasma or gamma globulin – antibodies distilled from the blood of healthy donors – can also help immunocompromised people, although a version of the latter that contains antibodies to the coronavirus is still months away from being available.

“It is a clear area where the need cannot be met,” said Hala Mirza, a spokeswoman for Regeneron, who made their monoclonal antibody cocktail available to a handful of immunocompromised patients through a compassionate application program. (Regeneron released experimental results this week showing the cocktail reduced symptomatic infections by 81 percent in people with normal immune systems.)

It is unclear how many immunocompromised people do not respond to coronavirus vaccines. But the list seems to include at least blood cancer survivors, organ transplant recipients, and anyone taking the widely available drug Rituxan or the cancer drugs Gazyva or Imbruvica – all of which kill or block B cells, the immune cells that develop antibodies – or Remicade, a popular one Drug used to treat irritable bowel disease. It can also include some people over the age of 80 whose immune responses have stalled with age.

“We are extremely concerned and interested in finding out how we can help these particular patients,” said Dr. Elad Sharon, an immunotherapy expert at the National Cancer Institute.

As the pandemic spread, doctors who specialized in treating blood cancer or caring for immunocompromised people expected at least some of their patients to encounter difficulties. Dr. Charlotte Cunningham-Rundles, an immunologist at the Icahn School of Medicine on Mount Sinai in New York, has about 600 patients who rely almost exclusively on regular doses of gamma globulin to protect against pathogens.

Nevertheless, 44 of their patients became infected with the coronavirus; four died and another four or five had long-term illnesses. (Chronic infections can give the virus the opportunity to develop into dangerous variants.)

Steven Lotito, 56, one of Dr. Cunningham-Rundles, was diagnosed with a condition known as common variable immunodeficiency when he was 13 years old. Before the pandemic, he had an active lifestyle, exercised, and ate well. “I’ve always known that I take special care of my body,” he said. This included infusions of gamma globulin every three weeks.

Despite careful precautionary measures, Mr Lotito caught the virus from his daughter in mid-October. He had a fever for almost a month and spent a week in the hospital. Convalescent plasma and remdesivir, an antiviral drug, provided relief for a few weeks, but his fever returned. After another infusion of gamma globulin that sweated through four shirts, he finally felt better.

Updated

April 15, 2021, 3:15 p.m. ET

Nevertheless, after almost seven weeks of illness, Mr. Lotito no longer had any antibodies to show. “I still have to take the same precautions that I took a year ago,” he said. “It’s a little daunting.”

People like Lotito-san rely on those around them to get vaccinated to keep the virus at bay, said Dr. Cunningham-Rundles.

“They hope that all of your family members and all of your close co-workers will go out and get a shot, and they will protect you with herd immunity,” she said. “You have to start with that.”

Dr. Cunningham-Rundles has tested their patients for antibodies and has registered some for Regeneron’s monoclonal antibody cocktail. However, many other people with these conditions are unaware of their risks or treatment options.

The Leukemia Lymphoma Society has set up a registry to provide information and antibody tests to people with blood cancer. Several studies are looking at the response to coronavirus vaccines in people with cancer, autoimmune diseases like lupus or rheumatoid arthritis, or in patients taking drugs that suppress the immune response.

What You Need To Know About The Johnson & Johnson Vaccine Break In The United States

    • On April 13, 2021, U.S. health officials called for an immediate halt to use of Johnson & Johnson’s single-dose Covid-19 vaccine after six recipients in the U.S. developed a rare blood clot disorder within one to three weeks of vaccination.
    • All 50 states, Washington, DC, and Puerto Rico have temporarily suspended use of the vaccine or suspended from recommended vendors. The U.S. military, government-run vaccination centers, and a variety of private companies, including CVS, Walgreens, Rite Aid, Walmart, and Publix, also paused the injections.
    • Fewer than one in a million Johnson & Johnson vaccinations are currently being studied. If there is indeed a risk of blood clots from the vaccine – which has yet to be determined – the risk is extremely small. The risk of contracting Covid-19 in the United States is much higher.
    • The hiatus could complicate the country’s vaccination efforts at a time when many states are facing spikes in new cases and are trying to address vaccine hesitation.
    • Johnson & Johnson has also decided to delay the launch of its vaccine in Europe amid concerns about rare blood clots, which is taking another blow to the vaccine surge in Europe. South Africa, devastated by a contagious variant of the virus found there, also stopped using the vaccine. Australia announced that it would not buy cans.

In one such study, British researchers tracked nearly 7,000 people with Crohn’s disease or ulcerative colitis from 90 hospitals across the country. They found that less than half of the patients who took Remicade had an immune response after contracting coronavirus infection.

In a follow-up, the scientists found that 34 percent of people who took the drug were protected after a single dose of the Pfizer vaccine and only 27 percent after a single dose of the AstraZeneca vaccine. (In the UK, the current practice is to delay second doses to increase vaccine availability.)

Likewise, another study published last month showed that fewer than 15 percent of patients with blood or immune cancer and fewer than 40 percent of patients with solid tumors produced antibodies after receiving a single dose of the Pfizer BioNTech vaccine.

And a study published last month in the journal JAMA reported that only 17 percent of the 436 transplant recipients who received a dose of the Pfizer BioNTech or Moderna vaccine had detectable antibodies three weeks later.

Despite the small likelihood, immunocompromised people should receive the vaccines because they may produce some immune cells that protect, even antibodies in a subset of patients.

“These patients should likely be prioritized for optimally balanced two doses,” said Dr. Tariq Ahmad, gastroenterologist with the Royal Devon and Exeter NHS Foundation Trust who was involved in the infliximab studies.

He suggested that doctors routinely measure antibody responses in immunocompromised people even after two doses of vaccine to identify those who may also need monoclonal antibodies to prevent infection or a third dose of the vaccines.

Wendy Halperin, 54, was diagnosed with a condition known as common variable immunodeficiency when she was 28 years old. She was hospitalized with Covid-19 in January and stayed there for 15 days. However, the coronavirus caused unusual symptoms.

“I had trouble walking,” she recalled. “I just lost control of my limbs like I couldn’t walk down the street.”

Since she was being treated for convalescence plasma for Covid-19, Ms. Halperin had to wait three months for the immunization and has made an appointment for April 26th. However, despite her condition, her body managed to produce some antibodies against the initial infection.

“The takeaway message is that everyone should try to get the vaccine,” said Dr. Amit Verma, oncologist at Montefiore Medical Center.

Gambling has settled in Dr. Wollowitz’s case not paid off. With no antibodies in his system to protect him, he still works from home – a privilege he is grateful for. He was an avid mountain biker and advanced skier, both of which were at risk of injury, but he is playing it safe with the coronavirus.

In anticipation of a return to his normal lifestyle, Dr. Wollowitz his bicycles. But he said he had foreseen he would live like this until enough other people are vaccinated and the number of infections in the city drops.

“I’m not exactly sure what that date is,” he said. “I’m really waiting to get out again.”

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