Post COVID-19 Syndrome and the Gut-lung Axis

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
Covid19

Intervention / Treatment
-----------------
* Dietary Supplement: Omni-Biotic Pro Vi 5
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Synbiotic<br>Omni-Biotic Pro Vi 5 | Dietary Supplement: Omni-Biotic Pro Vi 5<br>* Pre- and probiotic<br>|
| Placebo Comparator: Placebo<br>similar looking and tasting | Dietary Supplement: Placebo<br>* Placebo<br>|

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 |