Gastrointestinal Barrier Disruption in Post-COVID Syndrome Fatigue Patients, 2025, Rohrhofer et al.

[SNT Gatchaman]

Gastrointestinal Barrier Disruption in Post-COVID Syndrome Fatigue Patients
Johanna Rohrhofer; Viktoria Wolflehner; Johannes Schweighardt; Larissa Koidl; Michael Stingl; Sonja Zehetmayer; Joana Séneca; Petra Pjevac; Eva Untersmayr

BACKGROUND
Post-COVID Syndrome (PCS) is the term for a condition with persistent symptoms in a proportion of COVID-19 patients after asymptomatic, mild, or severe disease courses. Numbers vary, but the current estimate is that after COVID-19 approximately 10% develop PCS. The aim of our study was to evaluate the impact of SARS-CoV-2 infection on the gastrointestinal (GI) tract and associations with the development of PCS with fatigue, post-exertional malaise (PEM), orthostatic dysregulation, autonomous dysregulation, and/or neurocognitive dysregulation.

METHODS
By combining medical record data from a prospective observational study with symptom analysis before, during, and after SARS-CoV-2 infection, we aimed to identify potential risk factors and predictive markers for PCS. Additionally, we analyzed blood, saliva, and stool samples from this well-characterized PCS patient cohort to biologically validate our findings.

RESULTS
We identified significant associations between pre-existing GI complaints and the development of PCS Fatigue. PCS patients showed higher LBP/sCD14 ratios, lower IL-33 levels, and higher IL-6 levels compared to control groups. Our results highlight the critical role of the GI tract in PCS development of post-viral Fatigue.

CONCLUSION
We propose that the viral infection disrupts pathways related to the innate immune response and GI barrier function, 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 patients.

Link | PDF (Allergy) [Open Access]

 

[SNT Gatchaman]

All participants were recruited between April 2021 and August 2022 […] The study cohort consists of 30 PCS Fatigue patients, as well as 30 sex- and age-matched SARS- CoV-2 convalescent participants (SARS-CoV-2, convalescent), 16 SARS-CoV-2 naïve ME/CFS patients (ME/CFS) and 30 SARS-CoV-2 naïve healthy participants (Healthy) as controls.

ME/CFS was diagnosed based on the Institute of Medicine (IOM) criteria. All included ME/CFS patients suffered from an Epstein–Barr Virus (EBV)-related onset of the disease. For study participation, PCS patients had to suffer from Fatigue, PEM, and additionally from clinical signs of autonomous dysregulation, orthostatic dysregulation, and/or neurocognitive dysregulation. SARS- CoV-2 infected study participants had an asymptomatic or mild disease course, with four exceptions in the PCS group and two exceptions in the convalescent SARSCoV-2 control group.

 

[Hutan]

Funding: The project was partially supported by the WE & ME Foundation and the “Medizinisch-Wissenschaftlicher Fonds des Buergermeisters der Bundeshauptstadt Wien” (Medical-Scientific Fund of the Major of Vienna; project number: 22094).

It's nicely written up and each group, although small, is well matched.

Table 2 of pre-existing complaints is interesting.

Before the sampling, participants were asked to give a detailed medical record on their disease course and individual symptoms before, during, and after the SARS-CoV-2 infection, or their general health status for the SARS-CoV-2 naïve control participants

So, the 'before' is just before Covid-19 or 'general health status', so it's not pre-ME/CFS for the ME/CFS group, it's after ME/CFS onset. That makes some figures in Table 2 less useful for comparisons.

PCS Fatigue and ME/CFS patients reported a generally higher susceptibility to infections as indicated by frequently swollen lymph nodes, a sore throat, and frequent respiratory infections. Pre-existing food intolerances were observed more often in PCS Fatigue and ME/CFS patients. Only PCS Fatigue patients had significantly more pre-existing GI complaints.

POTS was reported by no PCS Fatigue group members, and only 37.5% (6) of the ME/CFS group.
50% of PCS-Fatigue people reported pre-existing GI symptoms before Covid-19; but only around 20% (3) of the ME/CFS group reported having GI symptoms - that was about the same percentage as the non-PCS Covid-19 group.

 

[Dolphin]

https://www.eurekalert.org/news-releases/1084706

News Release 21-May-2025
Post-COVID syndrome: connection between gut health and fatigue

Central role of the gastrointestinal tract in the development of long-term consequences after COVID-19

Peer-Reviewed Publication
Medical University of Vienna

In a recent study, a research team from the Medical University of Vienna has gained new insights into post-COVID syndrome (PCS) and the relevance of a healthy gastrointestinal tract. The study, which was recently published in the journal Allergy, shows that PCS patients have altered inflammatory markers and a disturbed intestinal barrier, which could contribute to the development of post-viral fatigue.

The researchers, led by Eva Untersmayr-Elsenhuber from MedUni Vienna's Center for Pathophysiology, Infectiology and Immunology, analyzed data from a prospective observational study. The course of SARS-CoV-2 infections and gastrointestinal symptoms before, during and after the infection were examined. In addition, blood, saliva and stool samples from PCS patients were analyzed.

The results show that patients with pre-existing gastrointestinal complaints have an increased risk of developing PCS fatigue. At the same time, prominent changes were found in certain biomarkers. For example, PCS patients showed an increased LBP/sCD14 ratio and lower IL-33 levels, which indicates altered immune activation and a reduced intestinal barrier. In addition, there were increased IL-6 levels, which are considered a marker for systemic inflammatory reactions.

"Our results suggest that SARS-CoV-2 infection can have long-term effects on the immune system and intestinal health that contribute to the development of PCS," explains Eva Untersmayr-Elsenhuber. She is co-director of the National Reference Center for Postviral Syndromes at MedUni Vienna.

Developing targeted treatment strategies
The study underlines the central role of the gastrointestinal tract in the development of long-term consequences after COVID-19. Monitoring gastrointestinal symptoms and biomarkers could help to identify at-risk patients at an early stage and develop targeted treatment strategies. This could be particularly important for the treatment of post-viral fatigue.

"What is particularly exciting is that our study participants were mostly young and healthy before the infection. Even the Covid disease was mostly mild or even asymptomatic. One difference was the more frequently reported gastrointestinal complaints in the group that developed post-viral fatigue," explains Johanna Rohrhofer from the Center for Pathophysiology Infectiology and Immunology, lead author of the study.
The research team plans to validate the findings in further studies. "The identification of predictive markers for PCS could enable personalized prevention and treatment in the future," says Eva Untersmayr-Elsenhuber.

Journal
Allergy

DOI
10.1111/all.16593

Article Title
Gastrointestinal Barrier Disruption in Post-COVID Syndrome Fatigue Patients

Article Publication Date
15-May-2025

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