Disrupted epithelial permeability as a predictor of severe COVID-19 development.

According to the epithelial barrier theory, the disruption of epithelial barriers by environmental and toxic agents results in microbial dysbiosis, bacterial translocation to subepithelial areas and local or systemic immune/inflammatory response to environmental agents, allergens and microbes. Chronic conditions like allergic, autoimmune and metabolic diseases have been linked to such events. Hyperinflammation, hyperactivated immune responses (known as the cytokine storm), cellular infiltration and organ damage are hallmarks of severe COVID-19 infections. The compromised epithelial barrier facilitates the translocation of microbiota and their secreted metabolites, thus initiating or exacerbating inflammatory cascades in many inflammatory diseases. A comprehensive study by Yazici et al. provides evidence that compromised epithelial barrier function is predicting severe COVID- 19, in line with the epithelial barrier theory. In this study, the amount of bacterial DNA leakage to circulation was analyzed and the link between disrupted epithelial barriers and an excessive inflammatory response was demonstrated. Major inflammatory proteins, including AREG, AXIN1, CLEC4C, CXCL10, CXCL11 and TRANCE correlated strongly with bacterial translocation and can be used to predict and discriminate severe COVID-19 cases from healthy controls and mild cases. Interestingly all of these analyses were done at the time of hospital admission even before severe symptoms occurred demonstrating that there is a link between certain protein biomarkers and disease progression from moderate to severe COVID-19 and death. These findings emphasize the value of early detection of biomarkers of epithelial barrier leakiness and bacterial translocation as indicators of poor disease outcome. They have implications on other infections, chronic diseases and may change the daily clinical practice and facilitate early therapeutic interventions.