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For over a year, Dr. Andrew Wollowitz has been mostly cloistered inside his home in Mamaroneck, NY.

As the medical director of emergency medicine at Montefiore Medical Center in the Bronx, Dr Wollowitz, 63, was eager to help treat patients when the coronavirus began to rage in the city last spring. . But cancer treatment in 2019 had wiped out his immune cells, leaving him defenseless against the virus, so he instead managed to manage his staff through Zoom.

A year later, the people in Dr. Wollowitz’s life are returning to some semblance 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 sit in his garden. “I spend very little time in public spaces,” he said.

Like his friends, Dr Wollowitz was vaccinated in January. But he didn’t produce any antibodies in response – and he wasn’t expecting it either. He is one of the millions of immunocompromised Americans whose bodies cannot learn to deploy immune fighters against the virus.

Some immunocompromised people are born with absent or defective immune systems, while others, like Dr. Wollowitz, have illnesses or have received therapies that have broken down their immune system. Many of them produce little or no antibodies in response to a vaccine or infection, making 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 may have put them at risk.

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

The only recourse for these patients – other than taking shelter until the virus has withdrawn – may be to receive regular infusions of monoclonal antibodies, which are mass-produced copies of antibodies obtained from people who have recovered from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 cleared several monoclonal antibody treatments for Covid-19, but some are now also 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 including antibodies to the coronavirus is still available in months.

“This is an area where unmet needs are evident,” said Hala Mirza, spokesperson for Regeneron, which has provided its cocktail of monoclonal antibodies to a handful of immunocompromised patients through a program of compassionate use. (Regeneron released test results this week showing the cocktail reduces symptomatic infections by 81% in people with normal immune systems.)

It is not known how many immunocompromised people do not respond to coronavirus vaccines. But the list seems to at least include blood cancer survivors, organ transplant recipients, and anyone who takes the widely used drug Rituxan, or the cancer drugs Gazyva or Imbruvica – which kill or block B cells, the immune cells that occur. antibody – or Remicade, a popular drug to treat inflammatory bowel disease. It may also include some people over the age of 80 whose immune responses have weakened with age.

“We are extremely concerned and interested in trying to see how we might be able to help these particular patients,” said Dr. Elad Sharon, an expert in immunotherapy 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 face difficulty. Dr Charlotte Cunningham-Rundles, an immunologist at the Icahn School of Medicine at Mount Sinai in New York City, has around 600 patients who depend almost entirely on regular doses of gamma globulin to stay safe from pathogens.

Even so, 44 ​​of his patients were infected with the coronavirus; four died and another four or five had long-term illnesses. (Chronic infections can give the virus an opportunity to progress to dangerous variants.)

Steven Lotito, 56, one of Dr Cunningham-Rundles’ patients, was diagnosed with Common Variable Immune Deficiency at the age of 13. Before the pandemic, he had an active lifestyle, exercised and ate well. “I’ve always known how to take a special kind of care of my body,” he says. This included infusions of gamma globulin every three weeks.

Despite special 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. Convalescent plasma and the antiviral drug remdesivir provided relief for a few weeks, but her fever returned. He eventually felt better after another infusion of gamma globulin, in which he sweated through four shirts.

Yet after nearly seven weeks of illness, Mr. Lotito had no antibodies to show. “I still have to take the same precautions I was taking, you know, a year ago,” he said. “It’s a little disheartening.”

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

“You are hoping that all of your family members and all of your close colleagues are going to come out and get vaccinated, and they are going to protect you with herd immunity,” she said. “This is where you have to start.”

Dr Cunningham-Rundles tested his patients for antibodies and signed a few for Regeneron’s monoclonal antibody cocktail. But many other people with such 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 cancers. And several studies are evaluating the response to coronavirus vaccines in people with cancer, autoimmune diseases like lupus or rheumatoid arthritis, or who take drugs that suppress the immune response.

In one of these studies, British researchers followed 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 developed an immune response after coronavirus infection.

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

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

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

Despite the low odds, people who are immunocompromised should still be vaccinated because they can produce protective immune cells, even antibodies in a subset of patients.

“These patients should probably be given priority for two doses at the optimal time,” said Dr Tariq Ahmad, gastroenterologist at the Royal Devon and Exeter NHS Foundation Trust who participated in the infliximab studies.

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

Wendy Halperin, 54, was diagnosed at age 28 with a condition called Common Variable Immunodeficiency. She was hospitalized with Covid-19 in January and stayed there for 15 days. But the coronavirus has induced unusual symptoms.

“I had difficulty walking,” she recalls. “I just lost control of my limbs, like I couldn’t walk the streets.”

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 his condition, his body managed to produce antibodies against the initial infection. .

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

The gamble did not bear fruit in the case of Dr Wollowitz. 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 at risk of injury, but with the coronavirus he’s playing it safe.

In anticipation of returning to his normal lifestyle, Dr. Wollowitz is adjusting his bikes. But he said he plans to live this way until enough more people are vaccinated and the number of infections in the city drops.

“I don’t know exactly what the date is,” he said. “I’m really waiting to leave.”





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