PARIS, April 2 (Benin News) –
Researchers from the University of North Carolina at Chapel Hill (USA) have revealed the biological reasons for the progression of COVID-19 and why a certain population of asthma patients is less likely to develop severe disease.
The vast majority of people infected with the omicron variant of SARS-CoV-2 have mild cold-like symptoms, moderate flu-like symptoms, or no symptoms, but the virus is so transmissible that it spreads still travels deep into lung tissue to cause severe illness and even death.
This research, published in the scientific journal “Proceedings of the National Academy of Sciences”, illustrates the importance of a well-known cytokine, interleukin-13 (IL-13), in protecting cells against COVID-19 , which helps explain the mystery of why people with allergic asthma cope better than the general population despite chronic lung disease.
The same is not true for people with other conditions, such as chronic obstructive pulmonary disease (COPD) or emphysema, who are at very high risk for severe COVID-19.
“We knew there had to be a biomechanical reason why people with allergic asthma seemed to be better protected against serious disease. Our research team discovered a number of important cellular changes, particularly due to IL-13, leading us to conclude that IL-13 plays a unique role in the defense against SARS- CoV-2 in certain patient populations,” says lead author Camille Ehre.
Although cytokines such as IL-13 cannot be used therapeutically because they trigger inflammation, it is important to understand the natural molecular pathways that cells use to protect themselves against invading pathogens. as these studies have the potential to reveal new therapeutic targets.
Many health factors increase the risk of severe COVID-19, including chronic lung diseases such as COPD, but as the pandemic progressed, epidemiologists found that people with allergic asthma were less likely to be seriously affected.
“These are patients with asthma caused by allergens, such as mould, pollen and dander. To find out why they are less sensitive, we studied specific cellular mechanisms in primary cultures of human airway epithelial cells,” says Ehre.
The researchers used genetic analysis of cultures of human respiratory tract cells infected with SARS-CoV-2 to find that expression of the human protein ACE2 governed the types of cells infected and the amount of virus present in that cell population. (also called viral load).
The scientists then used electron microscopy to identify an intense exodus of the virus from infected hair cells, which are cells responsible for moving mucus to the surface of the airways.
They also revealed severe cytopathogenesis, that is, changes inside human cells due to viral infection. And these changes result in the detachment of hair cells (filled with virions) from the surface of the airways.
“It is this shedding that provides a large viral reservoir for the spread and transmission of SARS-CoV-2. It also appears to increase the likelihood of infected cells moving deeper into the lung tissue,” says Ehre.
Further experiments with infected airway cells revealed that an important mucosal protein called MUC5AC was reduced inside the cells, likely because the proteins were being secreted in an attempt to trap invading viruses. But the viral load continued to rise as the cells responsible for producing MUC5AC were overwhelmed by rampant viral infection.
Researchers knew from epidemiological studies that patients with allergic asthma (known for its overproduction of MUC5AC) were less likely to suffer from severe COVID-19. Ehre and his colleagues also knew that the cytokine IL-13 increased MUC5AC secretion in the lungs when asthma patients were challenged with an allergen.
The scientists decided to mimic asthmatic airways by treating human airway cells with IL-13. They then measured viral titers, viral mRNA, shedding rate of infected cells, and total number of infected cells.
Each of them has been reduced significantly. They found that this remained true even when the mucus was removed from the cultures, suggesting that other factors are involved in the protective effects of IL-13 against SARS-CoV-2.
RNA sequencing analyzes revealed that IL-13 regulated genes controlling glycoprotein synthesis, ion transport and antiviral processes, all of which are important for airway immune defense. They also showed that IL-13 reduced expression of the viral receptor, ACE2, as well as the amount of virus inside cells and viral cell-to-cell transmission.
Taken together, these results indicate that IL-13 significantly affects the entry of the virus into cells, its replication in cells and its spread, thus limiting the ability of the virus to force its way into the respiratory tract. to cause serious illness.
“We believe this research further demonstrates how important it is to treat SARS-CoV-2 infection as early as possible. And it shows how important the specific mechanisms involving ACE2 and IL-13 are as we do everything we can to protect patients from developing serious infections,” concludes Ehre.