Post COVID-19 Syndrome and the Gut-lung Axis

Post COVID-19 Syndrome: A Pilot Study to Explore the Gut-lung Axis

The outbreak of the novel coronavirus (SARS-CoV-2)-infected disease (COVID-19) began in December 2019, spread throughout China in early 2020 and developed as a pandemic thereafter.

Based on current knowledge, Covid-19 infection causes mild to moderate respiratory and gastrointestinal symptoms in the majority of patients. In a smaller percentage severe disease courses are observed, often with the need of hospitalization and intensive care treatment. Apparently, symptoms can persist for relatively long time after viral clearance, suggesting the existence of a "Post-Covid" syndrome. A study from the UK identified fatigue, breathlessness and psychosocial stress as common symptoms after discharge from the hospital. Covid-19 infection is frequently characterized by a hyperinflammatory phenotype and a cytokine storm. The Covid-19 cytokine storm is characterised by rapid proliferation and hyperactivation of T cells, macrophages, mast cells, neutrophil granulocytes and natural killer cells, and the overproduction of inflammatory cytokines and chemical mediators released by immune or nonimmune cells. Early data also suggest that even if symptoms are just 'mild to moderate' during the acute infection, fibrotic lung damage develops in some patients. This may lead to long-term pulmonary complications for a subset of patients. The mechanisms for post-Covid pulmonary fibrosis are still unclear: inflammation triggering fibrosis, epithelial and endothelial injury with inadequate fibroproliferation and vascular damage are considered to be possible mechanisms.

A potential therapeutic target in ameliorating post-Covid symptoms could be the gut microbiome. Gut microbiome alterations have been described in Covid-19. The gut-lung axis as a link between dysbiosis, barrier dysfunction, translocation of bacterial products and hyperinflammation has been proposed as a potential therapeutic target. Probiotics have been proposed to be a possible modulator of the deranged gut-lung axis in Covid-disease and post-Covid syndrome. Currently 11 studies are registered in clinicaltrials.gov for treatment of acute Covid disease and prevention of the disease (including one study from Graz), but no study related to post-Covid syndrome could be found.

Therefore, it is currently unclear, which clinical, immune system or microbiome related biomarker would be the best to study the effect of a microbiome-based intervention in post-Covid syndrome.

Study Overview

• Status: Active, not recruiting
• Conditions: Covid19
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Omni-Biotic Pro Vi 5

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
    • Medical University Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18 years or older
• Covid-19 infection with severe disease defined within the last 12 months (defined as one or more of the following: hospitalization, need for oxygen supply, need for intensive care treatment, need for specific treatment of Covid disease, antibiotic treatment)
• Subjective presence of residual symptoms of Covid disease OR no residual symptoms of Covid disease (Controls)
• Informed consent

Exclusion Criteria:

• Continuous probiotic treatment in the last 4 weeks before inclusion
• Pre-existing lung diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Synbiotic; Omni-Biotic Pro Vi 5	Dietary supplement: Omni-Biotic Pro Vi 5; Pre- and probiotic
Placebo Comparator: Placebo; similar looking and tasting	Dietary supplement: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiome composition	16 sRNA sequencing	6 months
Intestinal barrier	Change in zonulin levels over time and with/without the intervention	6 months
sCD14	Change in sCD14 levels over time and with/without the intervention	6 months
endotoxin	Change in endotoxin levels serum over time and with/without the intervention	6 months
TNFalpha	Change in TNFalpha levels serum over time and with/without the intervention	6 months
Interleukin 1b	Change in Interleukin 1b serum levels over time and with/without the intervention	6 months
Interleukin 6	Change in interleukin 6 serum levels over time and with/without the intervention	6 months
Interleukin 6 receptor	Change in Interleukin 6 receptor serum levels over time and with/without the intervention	6 months
interleukin 8	Change in interleukin 8 serum levels over time and with/without the intervention	6 months
interleukin 10	Change in interleukin 10 serum levels over time and with/without the intervention	6 months
interleukin 17	Change in interleukin 17 serum levels over time and with/without the intervention	6 months
interleukin 23	Change in interleukin 23 serum levels over time and with/without the intervention	6 months
neutrophil function burst function	Change in neutrophil burst function over time and with/without the intervention	6 months
neutrophil function phagocytosis	Change in neutrophil phagocytosis function over time and with/without the intervention	6 months
neutrophil NET formation	Change in neutrophil NET formation over time and with/without the intervention	6 months
neutrophil surface receptor expression	Change in neutrophil surface receptor expression over time and with/without the intervention	6 months
monocyte burst	Change in monocyte burst over time and with/without the intervention	6 months
monocyte phagocytosis	Change in monocyte phagocytosis over time and with/without the intervention	6 months
monocyte function surface receptor expression	Change in monocyte surface receptor expression over time and with/without the intervention	6 months
T cell immunophenotyping	Change in T cell subtypes over time and with/without the intervention	6 months
B cells immunophenotyping	Change in B cell subtypes over time and with/without the intervention	6 months
Spirometry	Change in spirometry measurements over time and with/without the intervention	6 months
Lung volume	Change in lung volume over time and with/without the intervention	6 months
Gas diffusion	Change in pulmonary gas diffusion over time and with/without the intervention	6 months

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Collaborators: CBmed Ges.m.b.H.

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2021
• Primary Completion (Actual): July 11, 2022
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 15, 2021
• First Submitted That Met QC Criteria: March 23, 2021
• First Posted (Actual): March 24, 2021

Study Record Updates

• Last Update Posted (Estimated): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19
• Other Study ID Numbers: PostCov

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will be shared upon reasonable request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No