An Evaluation of a Synbiotic Formula for Patients With COVID-19 Infection

Not Applicable

• Conditions: Microbiota; Covid19
• Interventions: Other: Health supplements

• Registration Number: NCT04581018
• Lead Sponsor: Siew Chien NG

Brief Summary

In December 2019, a cluster of pneumonia cases of unidentified cause emerged in Wuhan,was identified as the culprit of this disease currently being identified as "Coronavirus Disease 2019" (COVID-19) by World Health Organization.

Coronavirus was found to not only target the patient's lungs but also multiple organs. Around 2-33% of Coronavirus Disease-19 patients developed gastrointestinal symptoms. Studies have shown that Severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2) was found in patient's feces, suggesting that the virus can spread through feces. 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.

The investigators are uncertain about the impact of synbiotic on patients with COVID-19. However, a therapeutic strategy aiming at investigating the gut Imicrobiota of patients with COVID-9 who take synbiotic or not, leading to lesser progression to severe disease, less hospital stay and improved quality of life.

Detailed Description

In December 2019, a cluster of pneumonia cases of unidentified cause emerged in Wuhan, Hubei province, China. In early January, a novel betacoronavirus forming another clade within the subgenus sarbecovirus, now named SARS-CoV-2, was identified as the culprit of this disease currently being identified as "Coronavirus Disease 2019" (COVID-19) by WHO.

Coronavirus was found to not only target the patient's lungs, but also multiple organs. Around 2-33% of COVID-19 patients developed gastrointestinal symptoms. Studies have shown that SAR-CoV-2 was found in patient's feces, suggesting that the virus can spread through feces. 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 million confirmed cases globally with 620 thousand deaths. Currently, there are more than 2000 confirmed cases of COVID-19 in Hong Kong. The investigators are uncertain about the impact of synbiotic on patients with COVID-19. However, a therapeutic strategy aiming at investigating the gut Imicrobiota of patients with COVID-9 who take synbiotic or not, leading to lesser progression to severe disease, less hospital stay and improved quality of life.

Study Timeline

• Study First Submitted: 2020-08-11
• Study Start: 2020-08-13
• Study First Submitted QC: 2020-10-06
• Study First Posted: 2020-10-09
• Primary Completion: 2021-12-31
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-01
• Last Update Posted: 2022-11-03
• Study Completion: 2023-07-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Aged 18 or above; and
2. 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 at recruitment and that require admission to the hospitalization area; and
3. Written informed consent is obtained

Exclusion Criteria

1. Subjects admitted to Intensive Care Unit or on ventilator

2. Known allergy or intolerance to the intervention product or its components

3. 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)

4. 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

5. Known history or active endocarditis

6. Recent on CAPD or hemodialysis-

7. Documented pregnancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Health supplements + standard care	Health supplements	28 days of health supplements (Synbiotic) daily plus standard care

Primary Outcome Measures

Name	Time	Method
Combined symptom score	4 weeks	Combined symptom score improvement of the first 4 weeks. Symptoms score assessment ranges from 20-80. The higher the score, the worse the symptoms.

Secondary Outcome Measures

Name	Time	Method
Clinical improvement	4 weeks	Compare the number and severity of symptoms existing by checking the list in symptoms assessment such as cough, shortness of breath, fever and gastrointestinal symptoms like anorexia, nausea, vomiting, abdominal pain, bloating before and during the study
Time to develop antibody against SARS-CoV-2	16 days	Compare the time to develop antibody against SARS-CoV-2 in both group
Quality of life measured by EQ-5D-5L	4 weeks	Improvement of quality of life measured by EQ-5D-5L. 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).
Quality of life measured by SF-12	4 weeks	Improvement of quality of life measured by SF-12. 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.
Duration of hospital stay	up to 3 months	Measure the duration of hospital stay in both group
Time to negative PCR	through study completion, an average of 1 year	Compare the time to negative PCR in both group
Trend of symptom score	4 weeks	Trend of symptom score, ranges from 26-104. The higher the score, the worse the symptoms.
Gastrointestinal symptoms	4 weeks	Duration of gastrointestinal symptoms such as anorexia, nausea, vomiting, abdominal pain, bloating within 4 week.
Changes in fecal bacteria metabolites	weeks 2, 4, 5 and 8 months 3, 6, 9 and 12	Changes in fecal bacteria metabolites measured by PCR at different time points
Change in plasma cytokines level	week 2 and week 5	Change in plasma cytokines level at week 2 and week 5 compared with baseline
Changes in the gut microbiome	weeks 1, 2, 3, 4, 5, 8 and months 3, 6, 9 and 12	Changes in the gut microbiome (bacteria, virome and fungome) measured by metagenomics at different time points (weeks 1, 2, 3, 4, 5 and months 3, 6, 9 and 12) compared to baseline
Number of admission to Intensive Care Unit	4 weeks	Number of admission to Intensive Care Unit
Number of subjects with home discharge	4 weeks	Number of subjects with home discharge
Number of mortality	4 weeks	Number of mortality
Number of days absent from work	3 months	Number of days absent from work since admission
Change of quality of life questionnaire	week 8, months 3, 6, 9 and 12	Change in score on Quality of life using EQ-5D-5L and SF-12. 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). While the 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.
Number of adverse event	3 months	Number of adverse event

Trial Locations

Locations (1)

The Chinese University of Hong Kong; 🇭🇰 Sha Tin, Hong Kong