When the COVID-19 pandemic first began, those with chronic lung conditions like asthma were anxious about the disease being particularly severe for them. However, it appears that people with some types of asthma are faring better than expected – and we might finally understand why.
Population-based studies in Australia, the UK and Europe, and the United States, have so far found no evidence that asthma drives severe symptoms of COVID-19.
In fact, it's just the opposite. Generally, people with allergic asthma are less likely to get really sick after catching SARS-CoV-2; this is in contrast to people with other lung conditions like emphysema, who are more likely to get severe symptoms.
So what sets asthma patients apart? Researchers at the University of North Carolina at Chapel Hill think they've finally figured it out.
To research this, the team used cell cultures from the human respiratory tract. To mimic the airways of asthmatic people, they treated some of the samples with a small protein known to be more prevalent in asthma, called interleukin-13 (IL-13). One of the things its presence causes in asthmatics is a ramping up of mucus production beyond healthy levels.
Then, the authors infected the cell cultures with SARS-CoV-2. In the IL-13-treated cells, the coronavirus showed trouble invading the cell to replicate and spread copies of itself. In untreated cells, meanwhile, there were many more infections.
"We knew there had to be a bio-mechanistic reason why people with allergic asthma seemed more protected from severe disease," says biochemist Camille Ehre from UNC.
"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."
When watching the respiratory cells and the virus interact under an electron microscope, Ehre and her colleagues noticed IL-13 treatments significantly diminished the number of infected cells, while increasing the mucus these cells produced.
Even when the mucus was removed, however, the cells still showed a degree of protection against the invading coronavirus.
RNA-sequencing further confirmed that the presence of IL-13 in the cell culture was upregulating genes linked to antiviral properties, while downregulating the expression of cell receptors that coronaviruses are known to attach to, like ACE2.
In untreated respiratory cells, these receptors allow a coronavirus to invade relatively easily. If a cell was really infected, researchers noticed it was more likely to shed away from the airway surface, allowing it to drop deeper into the lungs, thereby spreading the infection.
"In conclusion, intense viral and cell shedding caused by SARS-CoV-2 infection was attenuated by IL-13, which affected viral entry, replication, and spread," the authors conclude.
Unfortunately IL-13 can't be used as a treatment by itself. It is part of the immune response, which means it can trigger inflammation in a patient's airways.
But understanding the finer points of what's going on in the lungs is crucial nevertheless. By comparing cells that mimic asthmatic airways to healthy airway cells, scientists have highlighted some of the underlying mechanisms behind severe COVID-19 cases.
In the future, therapeutic drugs could help target certain sites that appear more involved in severe symptoms.
"We think this research further shows how important it is to treat SARS-CoV-2 infection as early as possible," says Ehre.
"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 was published in PNAS.