CHAPEL HILL, N.C. — Could pollen and seasonal allergens actually be protecting some people from COVID-19? Researchers in North Carolina found that people with allergic asthma are less likely to have a severe infection.
For people with allergic asthma, the same triggers which cause many people to sneeze when their allergies strike causes others to suffer an asthmatic attack. The study discovered the protective role interleukin-12 (IL-13) plays in the bodies of these individuals.
“We knew there had to be a bio-mechanistic reason why people with allergic asthma seemed more protected from severe disease,” says Camille Ehre, PhD, assistant professor of pediatrics at the UNC School of Medicine in a university release. “Our research team discovered a number of significant cellular changes, particularly due to IL-13, leading us to conclude that IL-13 plays a unique role in defense against SARS-CoV-2 infection in certain patient populations.”
Keeping COVID from spreading in the lungs?
Normally, researchers can’t use cytokines such as IL-13 in clinical treatments because they trigger inflammation. However, the researchers in the study still found it important to study their mechanism of action and how they protect cells from foreign invaders. Doing so has the potential to reveal new therapeutic targets beyond cytokine use.
The research team used genetic analysis of human airway cell cultures infected with SARS-CoV-2 (the virus causing COVID-19) to study the gene expression of human protein ACE2 on specific cell types and the amount of virus found in the cell population.
Scientists used electron microscopy to look at the amount of virus from infected ciliated cells, which move mucus along the airway surface. They also found massive changes inside human cells from viral infection. The changes accumulated in infected ciliated cells, causing the airway surface to gradually shed away.
“This shedding is what provides a large viral reservoir for spread and transmission of SARS-CoV-2,” Dr. Ehre says. “It also seems to increase the potential for infected cells to relocate to deeper lung tissue.”
A key protein may block the virus
Further experiments on infected airway cells uncovered a large reduction of the mucus protein MUC5AC. The team suggests the depletion may have come from excess protein secretion as cells tried to trap invading viruses. However, in a rampant viral infection, the cellular efforts were futile as the virus’s presence continued to grow.
The importance of MUC5AC drew interest from researchers who knew from previous studies that patients with allergic asthma overproduce MUC5AC and are less susceptible to severe COVID. Additionally, they also knew that when patients with asthma are exposed to an allergen, the cytokine IL-13 increases MUC5AC secretion in the lungs.
Mimicking the airways of people with asthma, they infected human airway cells and then treated them with IL-13. Their findings showed a significant decrease in the amount of virus in the lungs, the rate of infected cell shedding, and the number of infected cells. The reduction remained even when mucus was removed from the cell cultures, indicating IL-13 has multiple methods to defend against SARS-CoV-2.
RNA sequencing analysis showed the IL-13 upregulated genes involved in antiviral processes and airway immune defense. IL-13 also decreases ACE2 expression, which serves as the viral receptor.
“We think this research further shows how important it is to treat SARS-CoV-2 infection as early as possible,” Dr. Ehre concludes. “And it shows just how important specific mechanisms involving ACE2 and IL-13 are, as we try our best to protect patients from developing severe infections.”
The study is published in the Proceedings of the National Academy of Sciences.