Vaccinations do not protect millions of patients with weakened immune systems

Dr. Andrew Wollowitz has been classified in his home in Mamaroneck, NY, for over a year

As head of emergency medicine at Montefiore Medical Center in the Bronx, dr. Wollowitz, 63, was eager to help treat patients when the coronavirus began raging through the city last year. But a cancer treatment in 2019 wiped out his immune cells and left him defenseless against the virus, which is why he arranged to manage his staff via Zoom.

A year later, people turn in the life of dr. Wollowitz returns to a degree of normalcy. His wife, a dancer and choreographer, is preparing for work at the Austrian National Ballet Company. His vaccinated friends get together, but he only sees them when the weather is nice enough to sit in his backyard. “I spend very little time in public spaces,” he said.

Like his friends, Dr. Wollowitz was vaccinated in January. But he did not produce any antibodies, nor did he expect them. He is one of the millions of Americans who have immunocompromised, and whose bodies cannot learn to harness immune fighters against the virus.

Some immunocompromised people are born with an absent or defective immune system, while others, such as dr. Wollowitz, have had illnesses or received therapies that eradicate their immune defenses. Many of them produce little or no antibodies in response to a vaccine or an infection, making them susceptible to the virus. If they do become infected, they can suffer from long-term illnesses, with mortality rates of up to 55 percent.

Most people who have lived long with immune deficiencies are probably aware of their vulnerability. But others have no idea that medicine could endanger it.

“They will walk around outside thinking they are protected – but maybe not,” said Dr. Lee Greenberger, chief scientific officer of the Leukemia and Lymphoma Association, which funds research on blood cancer, said.

The only way to use these patients, except that it is in place until the virus has withdrawn, is to receive regular infusions of monoclonal antibodies, which are copies of antibodies in mass production obtained from people who have recovered from Covid-19 . The Food and Drug Administration has approved several monoclonal antibody treatments for Covid-19, but now some are also being tested to prevent infections.

Recovery plasma or gamma globulin – antibodies that are distilled from the blood of healthy donors – can also help people with weakened immune systems, although a version of the latter that contains antibodies to the coronavirus is still available for months.

“This is a clear area of ​​unmet need,” said Regeneron spokeswoman Hala Mirza through a compassionate use program to a handful of immunocompromised patients his monoclonal antibody cocktail. (Regeneron released test results this week showing that the cocktail reduces 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 it seems the list includes at least blood cancer survivors, organ transplant recipients and anyone using the drug Rituxan, or the cancer drugs Gazyva or Imbruvica – all of whom kill or block B cells, the immune cells that take out. Antibodies – or Remicade, a popular remedy for treating inflammatory bowel disease. It may also include people over the age of 80 whose immune responses have weakened with age.

“We are very concerned and want to be interested in helping specific patients,” said Dr. Elad Sharon, an expert in immunotherapy at the National Cancer Institute.

As the pandemic spread, doctors specializing in treating cancer or treating people with weakened immune systems expected at least some of their patients to experience problems. Dr. Charlotte Cunningham-Rundles, an immunologist at the Icahn School of Medicine on Mount Sinai in New York, has about 600 patients who depend almost entirely on obtaining regular doses of gamma globulin to stay safe against pathogens.

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

Steven Lotito (56), one of the patients of dr. Cunningham-Rundles, was diagnosed with a condition called generalized variable immunodeficiency when he was 13 years old. Before the pandemic, he had an active lifestyle, exercised and ate well. “I always knew I was taking special care of my body,” he said. This included infusions of gamma globulin every three weeks.

Despite careful precautions, Mr. Lotito contracted the virus from his daughter in mid-October. He had a fever for almost a month and spent a week in the hospital. Recovery plasma and inhibitor, an antiviral drug, provided relief for several weeks, but its fever returned. He finally felt better after another administration of gamma globulin, during which he sweated through four shirts.

After almost seven weeks of illness, Mr. Lotito has not yet had any antibodies to show for it. “I still have to take the same precautions I did a year ago,” he said. “It’s a little discouraging.”

People like Mr. Lotito is dependent on those around them who prefer to be vaccinated to keep the virus in check, said dr. Cunningham-Rundles said.

“You hope your entire family members and all your close colleagues will shoot, and protect them with herd immunity,” she said. “This is what you need to start with.”

Dr Cunningham-Rundles tested her patients on antibodies and enrolled a few for Regeneron’s monoclonal antibody cocktail. But many other people with such conditions are not aware of their risks or their treatment options.

The Leukemia and Lymphoma Association has set up a registry to provide information and antibody tests to people with blood cancer. Several studies have evaluated the response to coronavirus vaccines in people with cancer, autoimmune conditions such as lupus or rheumatoid arthritis, or drugs that dampen the immune response.

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

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

Similarly, another study published last month showed that less than 15 percent of patients with blood cancer or the immune system, and less than 40 percent of those with solid tumors, produce antibodies after taking a single dose of Pfizer-BioNTech vaccine received.

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

Despite the low chance, immune users still need to get the vaccines because it can produce some immune cells that are protective, even antibodies in a subgroup of patients.

“These patients should probably be prioritized for optimal two-dose time frame,” says Dr. Tariq Ahmad, a gastroenterologist at the Royal Devon and Exeter NHS Foundation Trust, who was involved in the infliximab studies.

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

Wendy Halperin, 54, was diagnosed at the age of 28 with a condition called common variable immune deficiency. She was hospitalized with Covid-19 in January and stayed there for 15 days. But the coronavirus caused unusual symptoms.

“I struggled to walk,” she recalls. “I just lost control of my limbs, as if I could not walk down the street.”

Because she was treated for Covid-19 with a recovery plasma, Ms. Halperin waited three months to be immunized and made an appointment for April 26. But despite her condition, her body managed to produce antibodies against the initial infection.

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

The venture did not bear fruit in the case of dr. Wollowitz does not. With no antibodies in his system to protect him, he still works from home – a privilege for which he is grateful. He was an avid mountain biker and advanced skier, both of whom carry the risk of injury, but with the coronavirus he plays it safe.

In anticipation of the return to his normal lifestyle, Dr. Wollowitz put his bikes in. But he said he would live like this until enough people were vaccinated and the number of infections in the city dropped.

“I do not know exactly what the date is,” he said. “I’m really waiting to come out again.”