Abstract
It is still controversial whether chronic lung inflammation increases the risk for COVID-19. One of the risk factors for acquiring COVID-19 is the level of expression of SARS-CoV-2 entry receptors, ACE2 and TMPRSS2, in lung tissue. It is, however, not clear how lung tissue inflammation affects expression levels of these receptors. We hence aimed to determine the level of SARS-CoV-2 receptors in lung tissue of asthmatic relative to age, gender, and asthma severity, and to investigate the factors regulating that. Therefore, gene expression data sets of well-known asthmatic cohorts (SARP and U-BIOPRED) were used to evaluate the association of ACE2 and TMPRSS2 with age, gender of the asthmatic patients, and also the type of the underlying lung tissue inflammatory cytokines. Notably, ACE2 and to less extent TMPRSS2 expression were upregulated in the lung tissue of asthmatics compared to healthy controls. Although a differential expression of ACE2, but not TMPRSS2 was observed relative to age within the moderate and severe asthma groups, our data suggest that age may not be a key regulatory factor of its expression. The type of tissue inflammation, however, associated significantly with ACE2 and TMPRSS2 expression levels following adjusting with age, gender and oral corticosteroids use of the patient. Type I cytokine (IFN-γ), IL-8, and IL-19 were associated with increased expression, while Type II cytokines (IL-4 and IL-13) with lower expression of ACE2 in lung tissue (airway epithelium and/or lung biopsies) of moderate and severe asthmatic patients. Of note, IL-19 was associated with ACE2 expression while IL-17 was associated with TMPRSS2 expression in sputum of asthmatic subjects. In vitro treatment of bronchial fibroblasts with IL-17 and IL-19 cytokines confirmed the regulatory effect of these cytokines on SARS-CoV-2 entry receptors. Our results suggest that the type of inflammation may regulate ACE2 and TMPRSS2 expression in the lung tissue of asthmatics and may hence affect susceptibility to SARS-CoV-2 infection.
Highlights
More than two years into this global pandemic crisis, there are still controversies surrounding the association of chronic respiratory diseases such as asthma and risk of infection with SARS-CoV-2 virus, the cause of coronavirus disease (COVID19)
It has been reported that the level of expression of SARS COV-2 receptors may determine the level of susceptibility of the lung tissue to SARS-CoV-2 infection [4]
We determined whether Angiotensin Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) are differentially expressed in the airway epithelium and lung tissue of large cohort of asthmatics
Summary
More than two years into this global pandemic crisis, there are still controversies surrounding the association of chronic respiratory diseases such as asthma and risk of infection with SARS-CoV-2 virus, the cause of coronavirus disease (COVID19). The fact that SARS-CoV-2 enters lung cells via ACE receptor [4] stimulated huge efforts to identify the factors that may directly or indirectly regulate level of expression of this receptor in the airway cells, and the risk for COVID-19 infectivity. In the context of asthma, the focus was mainly on the effect of selective asthma-specific cytokines such as IL-13 on the airway expression level of ACE2 [5, 6]. Our group found that Type II cytokines (IL-13, IL-5, and IL-4) were associated with reduced expression levels of ACE2 and TMPRSS2 in nasal tissues of eosinophilic chronic rhinosinusitis patients [7]. Better characterization of the effect of asthma-specific cytokines on ACE2 expression and on the infectivity and severity of COVID-19 infection is needed
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