BOSTON — In November, as American hospitals faced dire overcrowding, the US Food and Drug Administration gave emergency use authorization to two experimental treatments for COVID-19: Regeneron and bamlanivimab. The medications were fast-tracked for approval based on small studies that indicate that they decrease the odds that patients with COVID will require hospitalization.
Initial reports show that there has not been a single COVID-related death among any of the patients who received the monoclonal antibody infusions. More data is increasingly emerging from several doctors who treated thousands of COVID patients in high-risk categories — both the elderly, as well as patients with diabetes, high blood pressure, and obesity.
My own elderly grandparents both contracted COVID-19 and survived after receiving monoclonal antibodies. Seeing their recoveries, I wondered: Does the science support a more widespread use?
The US National Institute of Health (NIH) clearly states on its website that it does not recommend that doctors offer the treatment to their patients, but increasing numbers have started to turn to them, both in the US and in Israel.
In the US, Mayo Clinic Professor of Medicine Raymund Razonable has overseen the treatment of more than 2,000 elderly (those over 65) and high-risk patients with monoclonal antibody infusions at the Mayo Clinics in Minnesota, Wisconsin, Arizona and Florida since November 19. “No one has died the last time I checked,” he tells The Times of Israel.
Razonable’s data is not part of a double-blind study, and it has not yet been published in a scientific journal.
“I cannot release a lot of details because they might jeopardize the publication [in a scientific journal],” says Razonable. “But I am talking to you to encourage the use [of monoclonal antibodies]. Hopefully this is heard by other providers across the country.”
Dr. Howard Huang, who has supervised the treatment of approximately 1,400 high-risk COVID patients at the Houston Methodist Hospital in Texas, has seen similar results. Not one of his elderly or high risk patients died.
“No one. Zero mortality,” he says.
Stateside, there are some notable names among those who have received these monoclonal antibody infusions: former US president Donald Trump, former mayor of New York Rudy Giuliani, and former governor of New Jersey Chris Christie.
In the months since the emergency approval, the US doctors who have treated thousands of patients with the new monoclonal antibody drugs are reporting that there has not been a single death due to coronavirus among their recipients. Those treated include the elderly and others with elevated risk factors, such as diabetes, high blood pressure, and obesity.
In Israel, the Health Ministry told The Times of Israel that while the national vaccination campaign is already in full gear, “it is clear that the fight against the epidemic has not yet ended and until the entire population is vaccinated, solutions must be given to patients with the disease now.”
The treatment is another tool in the attending physician’s toolbox
Among them, said the Health Ministry, the Eli Lilly-produced bamlanivimab treatment “may be significant in preventing hospitalizations of particularly sensitive populations,” listing among them those have not developed immunity after vaccination, or are prevented from receiving the vaccine for various reasons.
“The treatment is another tool in the attending physician’s toolbox. Israel is among the first countries to guarantee their residents treatment outside the United States. The product is currently available in many hospitals,” wrote the Israeli Health Ministry. Regeneron, it noted, is currently only available in Israel and other countries outside of the US for clinical trials.
My grandparents’ story is similar to many who have been treated so far. As the global coronavirus pandemic rages on, it could potentially serve as a blueprint for success.
Hitting close to home
My grandmother, Sulamif Belenkiy, was a doctor in the former Soviet Union. Now 93, she has high blood pressure, diabetes, and lymphoma, but is mentally as sharp as ever. When my 92-year-old grandfather, Simon Belenkiy, came down with a fever in early December, my grandmother took care of him.
A few days later, however, she had a runny nose, a sore throat, fever, cough, and a headache. When they both tested positive for COVID-19, the whole family panicked.
At the Jewish community complex for the elderly where they live in Boston, the COVID statistics are chilling. Of the 68 residents who contracted the virus, 13 have died and so far 32 have recovered. The COVID death rate in Massachusetts stands at 20 percent for people over 80, and only increases for those in their 90s and above.
Our family began forming a plan of action. We had heard about the treatment that helped Trump, but neither of my grandparents’ doctors knew where to procure it. We searched online and found that a similar medication, bamlanivimab, had recently become available. Massachusetts received 600 doses for the first week of December. Every day that week, more than 6,000 people were diagnosed with COVID-19 in the state.
Getting the treatment was not easy. It involved calling a hospital in the middle of the night to get the sleepy attending physician on the line, tracking down the chief of the infectious diseases department, and faxing documents to CVS pharmacy’s Home Infusion Center — with my mother crying and begging on the phone. But it worked, and that Friday a nurse came to my grandparents’ apartment and stuck an IV into their arms.
Okay, let’s be guinea pigs for science
My grandmother was worried about the side effects. When she was young, she once had a severe reaction to a diphtheria vaccine. But now she steeled herself. “Okay, let’s be guinea pigs for science,” she said, before getting the infusion.
As the medication dripped into her vein, her fears dissipated. There were, surprisingly, no side effects. The next morning, when my grandparents woke up, their fevers were gone. The cough too, almost disappeared. They were very weak for a few days, but never developed shortness of breath and didn’t need to be hospitalized.
The situation was unfortunately different for their 93-year-old neighbor, who contracted the coronavirus in the same Russian-language daytime program for the elderly that my grandfather attends.
The neighbor’s grandson tried but failed to get his grandfather the monoclonal antibody infusion. One doctor hung up the phone on him. Another said he didn’t know anything about it. The neighbor was hospitalized and put on oxygen, then spent many days on a ventilator. His grandson said they had to put his bed in a closet, the hospital was so full.
He developed an infection in his lungs, a blood clot in his arm, and suffered a stroke. Recently, we learned that he died.
Just what are monoclonal antibodies?
Monoclonal antibodies are the first drugs that were designed specifically to fight COVID-19, and not repurposed from any existing treatments. They are synthetic replications of the antibodies that scientists found in the blood of patients who survived the disease.
Two medications received emergency use authorization from the FDA: bamlanivimab, and Regeneron, which uses a cocktail of two COVID-neutralizing antibodies. The one-time infusion must be administered within the first 10 days of symptom onset, but it works best when given within the first seven days.
“Our antibody cocktail mimics the way a healthy immune system behaves when exposed to a pathogen,” explains Regeneron’s spokeswoman Alexandra Bowie in an email to The Times of Israel. “We are selecting the best of these virus-neutralizing antibodies, scaling them up in a lab, and delivering them in a concentrated form to patients… [The antibodies bind to] the spike protein of the SARS-CoV-2 virus. The spike protein is the virus’s mechanism for entering healthy cells — by blocking this, we can stop infection.”
Monoclonal antibodies received emergency use authorization at the end of November based on two small studies that seemed to indicate that they decrease the chance that a COVID patient will need to be hospitalized. The initial study found that only 1.6% of patients treated with bamlanivimab required hospitalization (five out of 309 patients), compared with 6.3% of those who received the placebo (nine out of 143 patients).
The initial studies did not focus on elderly and high-risk patients. They found no difference in the mortality rates between those who were treated with monoclonal antibodies and those who were not, as none of the participants in the study died.
Now that doctors have been treating patients with monoclonal antibody infusions for about two months, some have stronger evidence that these medications not only prevent deaths but decrease hospitalization rates.
Among Razonable’s 2,000 patients at the Mayo Clinic, only 3% of infusion recipients had to be hospitalized, which is nearly five times lower than the Centers for Disease Control’s estimated 13.8% hospitalization rate for elderly COVID patients.
It does work as long as it’s given early
“It does work as long as it’s given early,” says Razonable.
The hospitalization rate among Huang’s elderly patients in Texas is about 4% — again, significantly lower than average for elderly people with COVID.
Patients who did need to be hospitalized spent only four days in the hospital on average — “relatively short compared to a lot of COVID cases,” says Huang.
“When you see that the hospitalization rate [in the field] looks similar to the clinical trial, it seems that there is something to what the clinical trial found,” he said.
Still, many hospitals and doctors continue to be reluctant to offer the new treatment.
Reasons for hesitance
According to a US government website, more than 400,000 doses of monoclonal antibody treatments have been delivered — and provided gratis — since November. But hundreds of thousands of Americans are diagnosed with COVID every day.
Currently, the US National Institute of Health (NIH) still does not recommend that doctors offer the treatment to their patients, stating on its website that “The relatively small number of participants and the low number of hospitalizations or emergency department visits make it difficult to draw definitive conclusions about the clinical benefit of bamlanivimab,” referring to the initial studies based on which the medications received emergency use authorization. “Bamlanivimab should not be considered the standard of care for the treatment of patients of COVID-19.”
The Infectious Diseases Society of America, which advises doctors, also recommends “against the routine use of bamlanivimab in ambulatory patients with COVID-19.”
The NIH guidelines are yet to be revised since thousands of COVID patients have been treated with monoclonal antibodies.
“These are still investigational drugs,” wrote NIH spokeswoman Hillary Hoffman in an email to The Times of Israel. “The COVID-19 Treatment Guidelines Panel notes there are insufficient data to recommend either for or against the use of bamlanivimab or casirivimab plus imdevimab [Regeneron] for the treatment of outpatients with mild to moderate COVID-19.”
These are still investigational drugs… The COVID-19 Treatment Guidelines Panel notes there are insufficient data to recommend either
Some in the public health community have also argued that monoclonal antibodies are simply “not worth the effort” because they are complicated to use. A recent article on NBC News quoted experts who explained the three issues involved: antibodies must be given intravenously, the infusion takes one hour, and the highly contagious patients must be kept apart from other patients.
Dr. Pieter Cohen, an associate professor at Harvard Medical School (who declined to be interviewed for this story) told NBC News that the monoclonal antibody treatments “are not a good use of our healthcare resources right now.”
Even Dr. Jorge Fleisher, the chairman of infectious diseases at Saint-Elizabeth Hospital in Boston who prescribed the monoclonal antibodies to my grandparents, initially said they most likely recovered because of their own immune systems.
Still, Fleisher has supervised the treatment of approximately 1,000 high-risk COVID patients with monoclonal antibodies. “I don’t know of anyone telling me that we had any bad outcomes,” he says, when asked if any of those patients have died.
There have been some side-effects from the infusion. Two people got rashes. One patient had a severe anaphylactic allergic reaction. Among the patients treated by Huang and Razonable, there have been no severe allergic reactions, but some had chills, skin rashes, nausea or felt flushed after the infusion. (Among Razonable’s 2,000 patients, 16 people reportedly felt some side-effects.)
Having witnessed my grandparents’ recovery, my grandmother’s primary care doctor Eugene Vaninov began offering the treatment to his other patients.
“When I found out that your grandma and grandpa started feeling better after just one day, I was amazed. I had two other patients, 89 and 87 years old. They both had COVID,” Vaninov says. “The 89-year-old was lying on the couch with a fever of 39 degrees [102.2 Fahrenheit], he couldn’t even move. After the infusion, he got up and said, ‘I want to dance.’”
Since Vaninov started prescribing bamlanivimab, none of his patients have died, he says, although he previously lost several patients.
“I can’t even have two opinions on this. When there is even a small chance, how can I deny a treatment to a patient when it can save their life?” Vaninov says. “I took the Hippocratic Oath.”