Evaluation of a Synbiotic Formula in Patient With COVID-19

Study Overview
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Brief Summary
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A series of microbiota were correlated inversely with the disease severity and virus load. Gut microbiota could play a role in modulating host immune response and potentially influence disease severity and outcomes.

Detailed Description
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Coronavirus can target multiple organs due to the hyperactive immune response with cytokine storms. Several studies have detected SARS-CoV-2 in stool samples and indicated that the virus could spread via faeces. Importantly, COVID-19 uses the same receptor as SARS and this doorway can also be found in the intestine. The cell entry receptor, known as angiotensin converting enzyme 2 (ACE2) receptor mediate entry of SARS-CoV-2 and is highly expressed in small bowel enterocytes. ACE2 is important in controlling intestinal inflammation and its disruption may lead to diarrhoea. In our previous study, stool samples from 15 patients with COVID-19 were analysed. Depleted symbionts and gut dysbiosis were noted even after patients were detected negative of SARS-CoV-2. A series of microbiota were correlated inversely with the disease severity and virus load. Gut microbiota could play a role in modulating host immune response and potentially influence disease severity and outcomes. In July 2020, there are more than 15 billion confirmed cases globally with 620 thousand deaths. Currently, there are more than 2000 confirmed cases of COVID-19 in Hong Kong. It is important to rebalance the gut microbiota in COVID-19 patients and to improve the symptoms and the quality of life of these patients.

Official Title
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Evaluation of a Synbiotic Formula in Patient With COVID-19

Conditions
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Coronavirus

Intervention / Treatment
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* Other: Health supplements


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 or above; and A confirmed diagnosis of SARS-Cov.2 infection using the PCR according to the standard of according to Centre for Health Protection, Department of Health, HK and released from isolation at recruitment. Written informed consent obtained Exclusion Criteria: Known allergy or intolerance to the intervention product or its components Any known medical condition that would prevent taking oral probiotics or increase risks associated with probiotics including but not limited to inability to swallow/aspiration risk and no other methods of delivery (e.g., no G/J tube) Known increased infection risk due to immunosuppression such as: Prior organ or hematopoietic stem cell transplant Neutropenia (ANC <500 cells/ul) HIV and CD4 <200 cells/ul Known increased infection risk due to endovascular due to: Rheumatic heart disease Congenital heart defect, Mechanical heart valves Endocarditis Endovascular grafts Permanent endovascular devices such as permanent (not short-term) hemodialysis catheters, pacemakers, or defibrillators Documented pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Health supplements<br>One arm only | Other: Health supplements<br>* tailor-made Synbiotics, 4g per day for 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in gut microbiome | Changes in the gut microbiome (bacteria, virome and fungome) measured by metagenomics at week 5 compared to baseline | week 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in fecal bacteria metabolites | Changes in fecal bacteria metabolites by PCR at different time points | weeks 2, 4, 5, 8 and months 3, 6, 9 and 12 | 
| Change in plasma cytokines including IL-6, IL-IB, TNF-a and CXCL-10 | Change in plasma cytokines level at week 5 compared with baseline | week 5 | 
| Trend in symptom score | Trend of symptom score at different time points, ranges from 26-104. The higher the score, the worse the symptoms. | weeks 2, 4, 5, 8 and months 3, 6, 9 and 12 | 
| Change in Quality of life measured by EQ-5D-5L | Change in score on Quality of life using EQ-5D-5L at different time points. EQ-5D-5L is a self-assessed, health related, quality of life questionnaire. The scale measures quality of life on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The index can be calculated by deducting the appropriate weights from 1, the value for full health (i.e. state 11111). Each category ranges from 1 to 5. The small the number, the better the health. The EQ-VAS is a vertical visual analogue scale that ranges 0-100 (higher score indicates better imaginable health). | weeks 2, 4, 5, 8 and months 3, 6, 9 and 12 | 
| Change in Quality of life measured by SF-12 | Change in score on Quality of life using SF-12 at different time points. SF-12 is a self-reported outcome measure assessing the impact of health on an individual's everyday life. There are formulas for transformation of scale scores so that they will range from 0-100. High score in functioning items indicates better functioning while high score in pain items indicates freedom from pain. | weeks 2, 4, 5, 8 and months 3, 6, 9 and 12 | 
| Duration of gastrointestinal symptoms | Duration of gastrointestinal symptoms such as anorexia, nausea, vomiting, abdominal pain, bloating within 4 weeks. | 4 weeks | 
| Adverse event assessment | Number of adverse event | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microbiota