Gut Barrier Disruption in Post-COVID Fatigue Raw sequence reads. Gut Barrier Disruption in Post-COVID Fatigue

Post-COVID Syndrome (PCS) is characterized by persistent fatigue, post-exertional malaise (PEM), as well as orthostatic, autonomic, and neurocognitive dysregulation. It occurs following SARS-CoV-2 infection, regardless of the severity of the disease course. Estimates suggest that approximately 10% of individuals develop PCS after COVID-19. Our study found that pre-existing gastrointestinal (GI) issues significantly increase the risk of developing PCS Fatigue. Patients with PCS Fatigue showed higher levels of inflammatory markers (LBP/sCD14 ratio and IL-6), lower IL-33 levels, and signs of GI barrier dysfunction, including low-grade intestinal inflammation. These findings suggest that viral infection disrupts pathways related to the innate immune response and GI barrier function, as evidenced by intestinal low-grade inflammation and GI barrier leakage. Monitoring GI symptoms and markers before, during, and after SARS-CoV-2 infection is crucial for identifying predictive clinical phenotypes in PCS. Understanding the interaction between viral infections, immune responses, and gut integrity could lead to more effective diagnostic and treatment strategies, ultimately reducing the burden on PCS Fatigue patients. Sequencing was performed at the Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna under the project ID JMF-2411-08.

新冠后综合征（Post-COVID Syndrome，PCS）以持续性疲劳、劳累后不适（post-exertional malaise，PEM）以及直立性、自主神经及神经认知调节异常为核心特征。该病症可发生于严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染后，且与感染病程的严重程度无关。据估算，约10%的感染者在感染新冠病毒后会罹患新冠后综合征。本研究发现，既往存在的胃肠道（gastrointestinal，GI）问题会显著增加罹患新冠后综合征疲劳型（PCS Fatigue）的风险。新冠后综合征疲劳型患者的炎症标志物[脂多糖结合蛋白/可溶性CD14比值（LBP/sCD14 ratio）与白细胞介素6（IL-6）]水平更高，白细胞介素33（IL-33）水平更低，且存在胃肠道屏障功能障碍迹象，包括轻度肠道炎症。上述研究结果表明，病毒感染会干扰固有免疫应答与胃肠道屏障功能相关的通路，这一点可通过轻度肠道炎症与胃肠道屏障渗漏得到证实。在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染前、感染期间及感染后监测胃肠道症状与标志物，对于识别新冠后综合征的预测性临床表型至关重要。阐明病毒感染、免疫应答与肠道完整性之间的相互作用，有望开发出更有效的诊断与治疗策略，最终减轻新冠后综合征疲劳型患者的疾病负担。本研究的测序工作由维也纳医科大学与维也纳大学联合微生物组中心（Joint Microbiome Facility）完成，项目编号为JMF-2411-08。