The vast majority of people infected with the Omicron variant of SARS-CoV-2 experience mild cold-like symptoms, moderate flu-like symptoms, or no symptoms at all. However, the variant is so transmissible that it spreads deep into lung tissue and can cause severe disease in some.
However, clinicians have found that, unlike those with certain comorbidities that increase the risk of severe COVID (including chronic obstructive pulmonary disease (COPD)), patients with allergic asthma seem less likely to develop complications. These patients are those who suffer precisely from forms of asthma caused by allergens, such as mold, pollen and dander.
MUC5AC and IL-13, 2 key protective proteins at high levels in asthma patients
The Chapel Hill researchers therefore deciphered the biological mechanisms linked to this protection of asthmatic patients against severe COVID and therefore analyzed primary cultures of human airway epithelial cells from these patients.
MUC5AC, a protective mucus protein: experiments conducted on these infected airway cells reveal that a major mucus protein called MUC5AC is depleted inside the cells and with this depletion the viral load keeps increasing as the cells responsible for producing MUC5AC are overwhelmed with the infection.
However, allergic asthmatic patients overproduce MUC5AC.
IL-13 (interleukin-13), a cytokine also plays a key role in protecting cells against SARS-CoV-2. The protein induces a number of important cellular changes: here, RNA sequencing analyzes reveal that IL-13 upregulates genes that control glycoprotein synthesis, ion transport and antiviral processes, all mechanisms important in the immune defense of the respiratory tract. In addition, IL-13 reduces 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-13a significantly affects viral entry into cells, replication within cells, and spread of the virus, and thus limits the ability of the virus to clear a path. way deeper into the airways.
However, IL-13 is more abundant in the airways of asthmatic patients.
When scientists replicate this benefit of asthmatic airways by treating human airway cells with IL-13, they find a decrease in viral load, shedding rate of infected cells, and total number of infected cells. . And this mechanism holds, even after removal of mucus from cultures, suggesting that other factors than mucus (and MUC5AC) are involved in these protective effects of IL-13 against SARS-CoV-2.
While cytokines like IL-13 cannot be used as therapies because they trigger inflammation, understanding this molecular and natural defense pathway used by cells to protect themselves from invading pathogens may may reveal new therapeutic targets, comments lead author Camille Ehre, a professor of pediatrics at UNC School of Medicine.
Taken together, these results show how important it is to treat SARS-CoV-2 infection as early as possible and suggest that the MUC5AC protein could be a possible therapeutic target to combat respiratory complications of COVID-19. .