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

Autor: Yazici D; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland., Cagan E; Department of Immunology, Bursa Uludag University School of Medicine, Bursa, Turkey.; Department of Pediatric Infectious Diseases, Bursa Yuksek Ihtisas Training and Research Hospital, University of Health Sciences, Bursa, Turkey., Tan G; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland., Li M; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland., Do E; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.; Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, California, USA., Kucukkase OC; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland., Simsek A; Department of Immunology, Bursa Uludag University School of Medicine, Bursa, Turkey., Kizmaz MA; Department of Immunology, Bursa Uludag University School of Medicine, Bursa, Turkey., Bozkurt T; Department of Immunology, Bursa Uludag University School of Medicine, Bursa, Turkey., Aydin T; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland., Heider A; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland., Rückert B; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland., Brüggen MC; Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.; Faculty of Medicine, University of Zurich, Zurich, Switzerland.; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland., Dhir R; SEED Inc. Co., Los Angeles, California, USA., O'Mahony L; Department of Medicine and School of Microbiology, University College Cork, Cork, Ireland.; APC Microbiome Ireland, Cork, Ireland., Akdis M; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland., Nadeau KC; Department of Environmental Health, T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA., Budak F; Department of Immunology, Bursa Uludag University School of Medicine, Bursa, Turkey., Akdis CA; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.; Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland., Ogulur I; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Jazyk: angličtina
Zdroj: Allergy [Allergy] 2023 Oct; Vol. 78 (10), pp. 2644-2658. Date of Electronic Publication: 2023 Jul 08.
DOI: 10.1111/all.15800
Abstrakt: Background: An impaired epithelial barrier integrity in the gastrointestinal tract is important to the pathogenesis of many inflammatory diseases. Accordingly, we assessed the potential of biomarkers of epithelial barrier dysfunction as predictive of severe COVID-19.
Methods: Levels of bacterial DNA and zonulin family peptides (ZFP) as markers of bacterial translocation and intestinal permeability and a total of 180 immune and inflammatory proteins were analyzed from the sera of 328 COVID-19 patients and 49 healthy controls.
Results: Significantly high levels of circulating bacterial DNA were detected in severe COVID-19 cases. In mild COVID-19 cases, serum bacterial DNA levels were significantly lower than in healthy controls suggesting epithelial barrier tightness as a predictor of a mild disease course. COVID-19 patients were characterized by significantly elevated levels of circulating ZFP. We identified 36 proteins as potential early biomarkers of COVID-19, and six of them (AREG, AXIN1, CLEC4C, CXCL10, CXCL11, and TRANCE) correlated strongly with bacterial translocation and can be used to predict and discriminate severe cases from healthy controls and mild cases (area under the curve (AUC): 1 and 0.88, respectively). Proteomic analysis of the serum of 21 patients with moderate disease at admission which progressed to severe disease revealed 10 proteins associated with disease progression and mortality (AUC: 0.88), including CLEC7A, EIF4EBP1, TRANCE, CXCL10, HGF, KRT19, LAMP3, CKAP4, CXADR, and ITGB6.
Conclusion: Our results demonstrate that biomarkers of intact or defective epithelial barriers are associated with disease severity and can provide early information on the prediction at the time of hospital admission.
(© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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