The impact of asthma in patients who develop COVID-19 has been a head-scratcher since the start of the pandemic. People with asthma and their physicians have worried that if they caught the coronavirus, the asthma could make them susceptible to severe illness.
Then some research showed that most asthmatics are at no higher risk for severe COVID-19 than the general population – and a good-sized population study even suggested they have a lower risk of hospitalization.
Now, a new study unveils biological factors that could explain why. Researchers have found that a signaling molecule that worsens allergic asthma actually helps to block the virus that causes COVID-19 from infecting respiratory cells in the lab.
Researchers showed that this cytokine, interleukin-13 (IL-13), also prevents a type of infected respiratory cell from shedding from the airways and spreading virus deeper into the lungs. IL-13 cytokines are known for setting off inflammation, and are present in higher levels in patients with allergic asthma, which is triggered by allergens such as mold, pollen and pet dander.
“We showed that IL-13, an inflammatory marker involved in allergic asthma, reduced both the number of viruses inside a cell and the number of cells that are detaching,” says senior study author Camille Ehre, PhD, an assistant professor at the University of North Carolina School of Medicine in Chapel Hill.
Lab Vs. Real World
But two leading asthma and immunology experts are not convinced. Lab findings often don’t translate to the real world, they say.
“A petri dish is vastly different from the human body,” says Dr. Mitchell Grayson, who studies viruses and is chief of allergy and immunology at Nationwide Children’s Hospital in Columbus, Ohio.
If IL-13 indeed offered powerful protection against the coronavirus, you would expect to see fewer infections among people with allergic asthma, and fewer getting sick – neither of which is true, says Dr. James Baker, director of the Mary H. Weiser Food Allergy Center at University of Michigan.
“We haven’t seen people with allergic asthma get fewer COVID-19 infections or have better outcomes,” says Baker, who authors a blog about the pandemic. Most studies show their risk of severe infections, he adds, is about the same as the general population.
Don’t Worry About Dupilumab
Furthermore, the case for IL-13 doesn’t hold up when you consider that biologic medications, such as dupilumab (Dupixent), inhibit IL-13. “There is nothing that suggests that people taking dupilumab have either increased risk of being infected, or higher viral [loads], or that they are doing worse if they are infected,” Grayson says.
In fact, a study by researchers at the Mount Sinai School of Medicine found patients taking dupilumab for eczema were more likely to have milder COVID-19 symptoms. And a follow-up study by those researchers found patients on dupilumab had lower antibody levels following COVID-19 infection, indicating they had a milder course of illness.
Both allergists say that if you’re talking dupilumab, you should absolutely continue taking it, without worries that it will raise your COVID-19 risks.
The Case for IL-13’s Effect
In the study, Ehre, who’s also a researcher at UNC’s Marsico Lung Institute, and her colleagues examined epithelial cell cultures from the respiratory tract that were infected with SARS-CoV-2, the virus that causes COVID-19.
Using a powerful electron microscope, they observed that the virus preferred infecting ciliated cells, a type of cell found in the airways. When damaged by the infection, ciliated cells form virus-filled sacs, which then shed. After detaching, the infected cells “are then free to travel deep into the lungs while loaded with viruses,” Ehre says.
“Within hours of infection, the damage can be so great that cells jam-packed with viruses detach from the cell surfaces and become ticking time bombs to infect either another person or another region of the lungs,” she told Allergic Living. “Such dramatic cellular events can explain the high transmissibility and high virulence of the novel coronavirus.” The team’s study was published in the Proceedings of the National Academy of Sciences (PNAS).
After applying IL-13 to the infected cell cultures, Ehre’s team found reduced expression of the ACE2 protein, which has been previously shown to be a “gateway” receptor that allows SARS-CoV-2 virus to enter the lungs.
In the lab tests, they also found that IL-13 reduced infection in ciliated cells, and there was less shedding. In addition, the researchers observed that IL-13 increased production of an important mucus protein that traps and disables viruses.
These findings apply only to allergic asthma, not other lung diseases or non-allergic asthma, Ehre says. Triggers of non-allergic asthma include respiratory infections, cigarette smoke, smog, exercise or stress.
Other Factors At Play
Grayson and Baker caution that how a virus behaves in the human body can be influenced by many, many factors.
While IL-13 may reduce the shedding of infected respiratory cells in a lab culture, to see the same effects in human beings, you might need much higher levels of IL-13 than anyone actually has, Grayson says.
Other factors that can influence how sick people get from COVID-19 include their age, body mass index (BMI), and whether they have other conditions, such as diabetes, which has been linked to higher risk of severe COVID-19 illness.
In addition, people with allergic asthma often take inhaled corticosteroids, which Baker notes are also used as a COVID-19 treatment. In those patients, he says the steroids might be what’s preventing hospitalization, not their IL-13.
Bottom line for people with allergic asthma? Don’t get complacent, the experts say.
People with allergic asthma need to complete their COVID-19 vaccinations if they haven’t already, Baker says. Also, take your medications as prescribed to make sure your asthma is controlled and that lung function is as good as it can be.
“We’re closing in on one million people in the U.S. dying of COVID,” Baker says. “We cannot just assume that some type of inflammatory cytokine will prevent the infection.”
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