University of North Carolina at Chapel Hill researchers have discovered scientific explanations for how disease progresses and why a specific group of asthma sufferers is less prone to severe COVID.
Scientists demonstrate how cells containing SARS-CoV-2 migrate deeply into the lungs, where severe COVID can establish itself, after detaching from the upper airway. Additionally, they learned how asthmatic reactions to allergens fight the virus and prevent the spread of severe COVID.
The majority of those infected with the omicron variant of SARS-CoV-2 have mild to moderate flu-like symptoms, or even no symptoms at all, but the virus is so contagious that it can still spread deeply into lung tissue and result in thousands of cases of severe illness and death in the United States in 2022 alone.
This study, which was published in Proceedings of the National Academy of Sciences, clarifies the significance of a well-known cytokine known as interleukin-13 (IL-13) in defending cells against SARS-CoV-2 and sheds light on the mystery of why people with allergic asthma fare better than the general population despite having a chronic lung condition. The same cannot be said for people who have other illnesses, such as emphysema or chronic obstructive pulmonary disease (COPD), which increase their risk of developing severe COVID.
It is crucial to comprehend the normal molecular pathways that cells utilise to defend themselves against pathogen invasion, even though cytokines like IL-13 cannot be used as therapeutics since they produce inflammation. These research could lead to the discovery of novel therapeutic targets. Chronic lung conditions like COPD are among the many health conditions that raise a person’s risk of developing severe COVID, but as the pandemic progressed, epidemiologists discovered that those with allergic asthma were less likely to develop severe disease.
Cameron Morrison, a medical student working in the Ehre lab, and Caitlin Edwards, an MPH student working as a research assistant in the lab of Ralph Baric, PhD, the Kenan Distinguished Professor of Epidemiology at the UNC Gillings School of Global Public Health and professor in the UNC Department of Microbiology and Immunology at the UNC School of Medicine, led the experiments.
The expression of the human protein ACE2 dictated which cell types were infected and the amount of virus present in this cell population, the researchers observed using genetic analysis of human airway cell cultures infected with SARS-CoV-2. The researchers next discovered a significant viral emigration from infected ciliated cells, which are cells responsible for pushing mucus along the surface of the airway. Extreme cytopathogenesis, or alterations to human cells brought on by viral infection, was also discovered by EM. Finally, these modifications result in the loss of ciliated cells that are virulently loaded from the surface of the airway.
A crucial mucus protein known as MUC5AC was found to be depleted inside of infected airway cells, according to further research. This is probably because the proteins were released in an effort to attempt and catch encroaching viruses. However, the virus load persisted because the cells responsible for generating MUC5AC were overburdened by a pervasive viral infection. Since allergic asthma patients are known to overproduce MUC5AC, epidemiological studies revealed that they were less likely to get severe COVID. Ehre and colleagues also understood that when asthma patients were exposed to an allergen, the cytokine IL-13 enhanced MUC5AC release in the lungs.
The researchers chose to use human airway cells treated with IL-13 to simulate asthmatic airways. The amount of infected cells overall, viral titers, viral mRNA, and the rate of infected cell shedding were all measured after that. Each one had a big decline. They discovered that this persisted even after the cultures’ mucus was removed, indicating that IL-13’s protective effects against SARS-CoV-2 may have been mediated by additional mechanisms.
To mimic asthmatic airways, the researchers decided to use human airway cells that had been treated with IL-13. Following that, the total number of infected cells, viral titers, viral mRNA, and the rate of infected cell shedding were all determined.
The decline was significant for each one. They found that this lasted even after the cultures’ mucus was taken out, suggesting that IL-13’s anti-SARS-CoV-2 actions may have been mediated by different pathways.