A hunch and hard work have led a University of Virginia medical research team to a clinical trial to determine if an allergy-related asthma drug can be used to treat COVID-19.
Research by Mary Young and Allie Donlan, part of Dr. William Petri’s medical research team, has led to a human trial of dupilumab, also known as Dupixent, to see if it can keep COVID patients off ventilators.
The drug currently is used for severe allergy-related eczema, asthma and chronic, long-term sinus inflammation.
“I’d hoped our clinical trial would fail simply because we couldn’t enroll enough COVID patients because COVID became so rare that we just can’t find any. Unfortunately, that didn’t happen,” Petri said. “We did enroll our first patient and, fortunately, he went home.”
Petri said he is unsure if the first patient received the dupilumab or a placebo as part of the trial.
“It’s a double-blind trial so I don’t know, but it’s pretty exciting to have a good result either way,” he said.
The trial is tied to a discovery last summer that UVa patients admitted into the COVID ward intensive care unit had large amounts of a particular molecule called Interleukin 13, or IL-13 for short.
IL-13 is a cytokine peptide, a creation of the immune system that’s often found in large quantities in patients suffering allergies, especially those with asthma and bronchitis. The peptide creates inflammation in response to allergies and infections and attracts other immune cells to help fight invaders.
It’s a way that white blood cells communicate with each other. If a cell makes IL-13, it activates other cells to go to where the IL-13 is located. Often it does its job too well, leading to large amounts of mucous buildup in the lungs, among other effects.
“There are several different forms of asthma, one of which is associated with allergies, and that’s the one where you have the cytokine with the unlucky number, IL-13,” Petrie said. “In this form of asthma, your body makes too much IL-13. As a result, it clogs up the lungs because it tells the lungs to make more mucous, makes the airways more reactive and a lot of other bad things.”
Most severe asthma was treated with steroids, the long-term use of which creates a host of physical problems. That led to the creation of dupilumab, a monoclonal antibody that inhibits IL-13 production.
Having researched the impacts of IL-13 on asthma, Petri’s researchers noticed the lung-related issues with COVID seemed similar. They devised a plan to test those admitted for treatment for levels of IL-13.
“It’s the lungs failing that bring people into the hospital for COVID, so we were prepared to look for that,” Petri recalled. “We set it up in March 2020, before the first patient got admitted to UVa, to get permission to save leftover samples of blood drawn from patients when they’re admitted to the hospital. There’s always a little left over in case they need to test for something else and then it’s thrown away.”
Petri said Young came in every day during the pandemic to collect the left-over blood. Donlan, who recently received her doctorate from UVa based on the research, tested the samples for the many interleukins created in the immune system.
The hunch that IL-13 could be a culprit was correct.
“You can measure like 48 different interleukins, and we found that, sure enough, IL-13 was the one associated with patients going onto ventilators,” Petri said. “If you were admitted, and you were in the top half of people with IL-13 levels in your blood, you were more than twice as likely to end up on a ventilator.”
That led to another hunch. If IL-13 blocking agents worked for asthma, they might work for COVID. In a database of millions of patients hospitalized for COVID-19, the researchers found that high levels of IL-13 were associated with worsened outcomes regardless of patient gender, age or health problems.
They also found patients with severe asthma taking dupilumab did not die from COVID.
“The data showed that, if you were on dupilumab and by chance got COVID 19, you had a 100% survival rate,” he said. “We had 80 people with asthma on dupilumab and 100% survived. We had hundreds who had asthma but weren’t on the drug and 95% survived, meaning 5% died.”
Figures may not lie, but it’s best to test them. The researchers created a test in which mice with COVID-19 were treated with the drug. The drug blocked the cytokine, which blocked the creation of mucous in the lungs, lessening COVID’s severity.
Turning it around, IL-13 was introduced into some of the mice, which worsened the symptoms.
Based on the research, the team led by clinical researcher Dr. Jen Sasson, of UVa, received approval from the U.S. Food and Drug Administration for a human clinical trial of dupilumab’s effectiveness on COVID.
The research is funded by local philanthropist Paul Manning, of PBM Capital and Virginia Catalyst, which provides grants for bioscience health research.
“I find this exciting because I never thought I’d be involved in applying to the FDA for an investigative drug approval,” Petri said. “It’s also exciting to see Allie and Jen and Mary making this discovery and then taking it to trial. It’s every professor’s dream to be involved in this and, more importantly, to have their students discover it. It’s been a wonderful experience.”