SIAF: Disrupted epithelial barriers as a predictor of severe COVID-19 development

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Severe Covid-19 in epithelial barrier disrupted subjects

DAVOS, Switzerland, July 10, 2023 /PRNewswire/ -- According to the epithelial barrier theory, disruption of epithelial barriers by environmental and toxic agents triggers microbial dysbiosis, bacterial translocation to subepithelial areas and local or systemic immune/inflammatory response to environmental agents, allergens and microbes. Such events have been implicated in the development of chronic conditions like allergic, autoimmune, and metabolic diseases, such as diabetes, obesity, rheumatoid arthritis, allergies, asthma, atopic dermatitis. In severe cases of COVID-19, characteristic features include hyperinflammation, hyperactivated immune responses (referred to as the cytokine storm), cellular infiltration, and organ damage.

Biomarkers of intact or defective epithelial barriers are associated with disease severity

The compromised epithelial barriers in the mucosas, particularly in gut mucosa facilitates the translocation of microbiota and their secreted metabolites, thus initiating or exacerbating inflammatory cascades in many inflammatory diseases. The research group of epithelial biology in the Swiss Institute of Allergy and Asthma Research, associated with the University of Zurich, has been working on epithelial barriers for more than 20 years. Today they have published a study in Allergy, Journal of the European Academy of Allergy and Clinical Immunology providing substantial evidence that epithelial barrier function is compromised in particularly severe COVID-19 patients, which is also in line with the epithelial barrier theory. The authors analyzed the amount of bacterial DNA leakage to circulation and showed the link between disrupted epithelial barriers and an excessive inflammatory response. They identified other major inflammatory proteins, 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. 

Free Access Link to the article for further reading: http://doi.org/10.1111/all.15800

Correspondence: Ismail Ogulur, Cezmi A. Akdis
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