Clinical trial NCT04813718: Post COVID-19 Syndrome and the Gut-lung Axis
Official title: Post COVID-19 Syndrome: A Pilot Study to Explore the Gut-lung Axis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Covid19
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
Collaborators: name: CBmed Ges.m.b.H.
First posted: 2021-03-24
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


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

Primary outcomes:
measure: Microbiome composition
timeFrame: 6 months
measure: Intestinal barrier
timeFrame: 6 months
measure: sCD14
timeFrame: 6 months
measure: endotoxin
timeFrame: 6 months
measure: TNFalpha
timeFrame: 6 months
measure: Interleukin 1b
timeFrame: 6 months
measure: Interleukin 6
timeFrame: 6 months
measure: Interleukin 6 receptor
timeFrame: 6 months
measure: interleukin 8
timeFrame: 6 months
measure: interleukin 10
timeFrame: 6 months
measure: interleukin 17
timeFrame: 6 months
measure: interleukin 23
timeFrame: 6 months
measure: neutrophil function burst function
timeFrame: 6 months
measure: neutrophil function phagocytosis
timeFrame: 6 months
measure: neutrophil NET formation
timeFrame: 6 months
measure: neutrophil surface receptor expression
timeFrame: 6 months
measure: monocyte burst
timeFrame: 6 months
measure: monocyte phagocytosis
timeFrame: 6 months
measure: monocyte function surface receptor expression
timeFrame: 6 months
measure: T cell immunophenotyping
timeFrame: 6 months
measure: B cells immunophenotyping
timeFrame: 6 months
measure: Spirometry
timeFrame: 6 months
measure: Lung volume
timeFrame: 6 months
measure: Gas diffusion
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University Graz
Study officials:
References: