Impairment of Esophageal Barrier Integrity: New Insights into Esophageal Symptoms in Post-COVID-19

Abstract

Background: The COVID-19 pandemic, caused by SARS-CoV-2, has unveiled a range of symptoms beyond the respiratory system, including significant gastrointestinal manifestations. Aims: This study explores the prevalence and intensity of gastroesophageal symptoms in post-COVID-19 patients and the integrity of the esophageal epithelial barrier. Methods: We conducted a prospective longitudinal cohort study with 55 patients hospitalized due to COVID-19 at a University Hospital. Patients were evaluated during hospitalization and between 3 and 6 months post-discharge, using validated questionnaires for gastrointestinal and gastroesophageal reflux symptoms. Additionally, 25 of these patients underwent upper digestive endoscopy, with esophageal mucosal biopsies analyzed for transepithelial electrical resistance (TER), permeability, and expression of inflammatory cytokines and cell junction proteins. Data expressed as mean EPM, inference by two-way ANOVA. Results: Results were considered statistically significant at p < 0.05. There were significant increases in heartburn and acid reflux symptoms in post-COVID-19 patients, as measured by the GSRS questionnaire. Biopsies from post-COVID patients revealed increased esophageal permeability when compared to non-COVID patients in acidic media (pH 2: non-COVID-19: 717.8 ± 168.2 vs. post-COVID-19: 1377.6 ± 316.4), suggesting compromised mucosal barrier. Furthermore, IL-8 levels and expression of Claudin-2 were elevated in these patients. Conclusions: The data suggested that COVID-19 infection may cause lasting damage to the esophageal epithelial barrier, increasing its permeability and provoking an exacerbated inflammatory response. These changes may explain the prevalence of post-infection gastroesophageal symptoms. Our findings underscored the importance of continuous monitoring and the development of therapeutic strategies to mitigate gastroesophageal effects in patients recovering from COVID-19.