Vaccines will not protect millions of patients with weakened immune systems

Dr. Andrew Wollowitz has been locked up in his home in Mamaroneck, NY for more than 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 to make headlines around the city last spring. But a cancer treatment in 2019 wiped out his immune cells, leaving him defenseless against the virus, so instead he arranged to manage his staff through Zoom.

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

Like his friends, Dr. Wollowitz was vaccinated in January. But he didn’t produce antibodies in response – and he didn’t expect it. He is one of millions of immunocompromised Americans whose bodies cannot learn to fight the virus.

Some immunocompromised people are born with absent or defective immune systems, while others, such as Dr. Wollowitz, have diseases or received therapies that have cleared their immune system. Many of them produce few or no antibodies in response to a vaccine or infection, leaving them susceptible to the virus. When infected, they can suffer from prolonged illness, with death rates of up to 55%.

Most people who have lived with immune deficiencies for a long time are likely to be aware of their vulnerability. But others have no idea that the drugs would have endangered them.

“They will walk outside thinking they are protected – but maybe not,” said Dr. Lee Greenberger, chief executive of the Society for Leukemia and Lymphoma, which funds blood cancer research.

The only recourse for these patients – apart from sheltering on the spot until the virus has receded – may be to receive regular infusions of monoclonal antibodies, which are mass-produced copies of antibodies obtained from people who have recovered from Covid. -19. The Food and Drug Administration has authorized several monoclonal antibody treatments for Covid-19, but some are now being tested to prevent infections.

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 includes antibodies to coronavirus is still a few months away from availability.

“It’s a clear area of ​​unmet need,” said Hala Mirza, a spokeswoman for Regeneron, which provided its cocktail of monoclonal antibodies to a handful of immunocompromised patients through a compassionate use program. (Regeneron published the results of studies this week showing that the cocktail reduces symptomatic infections by 81% in people with normal immune systems.)

It is unclear how many immunocompromised people do not respond to coronavirus vaccines. But the list appears to include at least blood cancer survivors, organ transplant recipients, and anyone taking the widely used drug Rituxan or Gazyva or Imbruvica cancer drugs – all of which kill or block B cells, antibody-producing immune cells – or Remicade, a popular medicine for treating inflammatory bowel disease. It may also include some people over the age of 80 whose immune responses have faltered with age.

“We are extremely concerned and interested in trying to see how we can help those patients,” said Dr. Elad Sharon, an immunotherapy expert at the National Cancer Institute.

As the pandemic spread, doctors specializing in treating blood cancers or caring for immunocompromised people expected at least some of their patients to have difficulty. Dr. Charlotte Cunningham-Rundles, an immunologist at Mount Iinahn School of Medicine in New York’s Sinai, has about 600 patients who are almost entirely dependent on getting regular doses of gamma globulin to stay safe from pathogens.

Even so, 44 ​​of her patients were infected with coronavirus; four died and another four or five had long-term illness. (Chronic infections can provide opportunities for the virus to develop into dangerous variants.)

Steven Lotito, 56, one of Dr. Cunningham-Rundles’ patients, was diagnosed with a condition called common variable immune deficiency at the age of 13. Before the pandemic, he had an active lifestyle, exercised and ate well. “I always knew I had special care for my body,” he said. This included gamma globulin infusions every three weeks.

Despite taking precautions, 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. Plasma and remdesivir, an antiviral drug, provided relief for several weeks, but his fever returned. He finally felt better after another gamma globulin infusion, during which he sweated through four shirts.

However, after almost seven weeks of illness, Mr. Lotito had no antibodies to show for it. “I still have to take the same precautions we did, you know, a year ago,” he said. “It’s a little discouraging.”

People like Mr. Lotito depend on those around them who choose to be vaccinated to keep the virus at bay, Dr. Cunningham-Rundles said.

“We hope that members of the whole family and all close colleagues will come out and be shot and will protect you with the immunity of the herd,” she said. “That’s what you have to start with.”

Dr. Cunningham-Rundles tested his patients for antibodies and signed a few for the Regeneron monoclonal antibody cocktail. But many other people with such conditions are unaware of their risks or treatment options.

The Society for Leukemia and Lymphoma has created a registry to provide information and antibody tests to people with blood cancer. Several studies are evaluating the response to coronavirus vaccines in people with cancer, autoimmune conditions such as lupus or rheumatoid arthritis, or taking drugs that disable the immune response.

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

Following a study, scientists found that 34% of people taking the drug were protected after a single dose of Pfizer vaccine and only 27% after a single dose of AstraZeneca vaccine. (In the UK, the current practice is to delay the second dose to extend vaccine availability.)

Also, another study published last month indicated that less than 15% of patients with blood or immune system cancer and less than 40% of those with solid tumors produced antibodies after receiving a single dose of Pfizer vaccine. -BioNTech.

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

Despite the low chances, immunocompromised people should continue to receive vaccines because they can produce some immune cells that are protective, even antibodies in a subgroup of patients.

“These patients should probably have priority for two optimally timed doses,” said Dr Tariq Ahmad, a gastroenterologist at the Royal Devon and Exeter NHS Foundation Trust, who has been involved in studies with infliximab.

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

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

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

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

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

The bet didn’t work for Dr. Wollowitz. With no antibodies in his system to protect him, he still works from home – a privilege for which he is grateful. He was a passionate motorcyclist and an advanced skier, both at risk of injury, but he plays with the coronavirus safely.

While waiting for his return to his normal lifestyle, Dr. Wollowitz prepares his bicycles. But he said he planned his life like that until enough people were vaccinated and the number of infections in the city was declining.

“I’m not exactly sure what that date is,” he said. “I’m really looking forward to coming back.”