The asthma paradox. Because Covid-19 is primarily a respiratory disease, people with chronic respiratory conditions such as asthma were thought to be at greater risk of contracting the coronavirus. In contrast, epidemiological studies have shown that asthmatics were not overrepresented among patients with severe Covid, except for a minority with severe asthma (about 5% of asthmatics). A study published March 30, 2022 in PNAS sheds light on this paradox by showing how the weaknesses of allergic asthmatics have become their strengths during the pandemic.
Asthmatics are protected by several barriers
“We knew there had to be a biomechanical reason that could explain why some asthmatics seemed to be protected from severe Covid,” says Camille Ehre, a researcher at the University of North Carolina at Chapel Hill (USA) and author of the study in reported. All that remained was to find him. In particular, this protection seemed to be specific to people with allergic asthma. This is triggered in the presence of allergens such as pollen or mold, which activate the production of cytokines and mucin in the patient’s lungs. In particular, the mucin MUC5AC, which is secreted by some lung cells during respiratory infections and which is produced in excess in asthmatics. This mucin production is regulated by interleukin 13 (IL-13), an anti-inflammatory cytokine that is overexpressed in asthmatics.
The first mucin barrier blocking the virus
The researchers mimicked asthma with lung cells treated with this interleukin 13 and then infected them with the SARS-CoV-2 coronavirus. So they showed that Covid protection plays out on multiple levels. First, the overproduction of mucin created a physical barrier that somewhat protected these cells from infection. In untreated cells, mucin secretion also increased after infection, but these cells were quickly suppressed, and the amount of mucin was insufficient to cope with virus multiplication.
The second barrier, removing the entrance doors to the cells
But this barrier was not the only one. Because even cells in which the production of the MUC5AC mucin was blocked showed a lower viral load due to the interleukin treatment. The second barrier was the reduced availability of lung cells to coronavirus, because this cytokine reduced the production of the ACE-2 receptor, the entry point of the virus into our cells. Finally, treated lung cells produced fewer SARS-CoV-2 virions after infection, thereby protecting surrounding cells. “It is this release of the virus into the lungs that gives the coronavirus its greater ability to transmit and seems to increase its potential to infect deeper lung tissues,” explains Camille Héré.
Additional hurdles to find out
Other mechanisms could also be involved in this protection, as the authors noticed that the expression of other genes was upregulated by treatment with interleukin IL-13. Together, these cellular changes led to a significant reduction in virus entry into lung cells, replication, and spread to other cells. “This study shows the importance of some specific mechanisms associated with IL-13 expression and how this can be used to protect patients and prevent them from developing severe forms of Covid,” the researcher concludes. These results also show how important it is to treat a coronavirus infection as early as possible, before the lung cells become infected.