A Randomised-controlled Trial of an Oral Microbiome Immunity Formula in Recovered COVID-19 Patients

Study Overview
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Brief Summary
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This study aims to evaluate the effectiveness of an oral microbiome immunity formula in modulating gut microbiota, enhancing immunity and reducing long-term complications and co-morbidities in patients who have recovered from COVID-19.

Detailed Description
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SARS-CoV-2, the cause of COVID-19, emerged as a new zoonotic pathogen of humans at the end of 2019 and rapidly developed into a global pandemic. It may develop severe or critical disease with respiratory failure requiring oxygen support and intensive care. Natural infection by virus triggers an effective system immunity so that the host can resist or highly reduce the chance of re-infection. In many cases, this protection can maintain a long period of time. However, the long-term immunities (over a year) and complications from the patients are not yet very clear. We found that COVID-19 survivors who have cleared the virus continued to have persistent altered gut microbiota and up to 80 percent had residue COVID-19 related symptoms including fatigue, difficulty in breathing, impaired memory and hair loss up to 6 months after discharge (LONG COVID-19). Earlier studies from our CU Medicine have shown a link between altered gut microbiome and COVID-19 severity, and more patients who received a novel microbiome immunity formula (SIM01) achieved complete symptom resolution and developed neutralising antibody than those who did not (unpublished data). Research from the Faculty also reported that almost 40% of people in Hong Kong had significant gut dysbiosis especially in elderly and patients with diabetes, obesity or chronic diseases. This study is a single-centre, triple-blind, randomized, placebo-controlled clinical trial that aims to evaluate the effectiveness of an oral microbiome immunity formula (SIM01) invented by the Chinese University of Hong Kong (CUHK) in modulating gut microbiota, enhancing immunity and reducing long-term complications and co-morbidities (e.g. sepsis, cardiopulmonary complications, metabolic syndrome, neuropsychiatric disorders) in patients who have recovered from COVID-19.

Official Title
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A Randomised-controlled Trial of an Oral Microbiome Immunity Formula in Reducing Development of Long-term Co-morbidities in Recovered COVID-19 Patients

Conditions
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COVID-19, Probiotic

Intervention / Treatment
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* Dietary Supplement: Microbiome immunity formula
* Dietary Supplement: Active placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals aged 18 and above; Subjects who are mentally capable to participate in the study and provide informed consent; Subjects who can communicate in Chinese or English; Subjects who are ambulatory and do not have difficulties travelling to the clinics for follow-up; Subjects who do not have plans to leave Hong Kong in the subsequent two years after recruitment; and Subjects who agree to give informed consent voluntarily. Exclusion Criteria: Subjects who are unable to receive oral fluids; Subjects who have received surgery involving the intestine within past 30 days; Subjects who are pregnant or breastfeeding; and Subjects who are immunocompromised, e.g. on cancer treatment, bone marrow/organ transplant, immune deficiency, poorly controlled HIV/AIDS.

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active arm<br>Subjects will take microbiome immunity formula (SIM01) daily for 6 months | Dietary Supplement: Microbiome immunity formula<br>* Microbiome immunity formula contains probiotics blend (3Bifidobacteria, 20 billion CFU daily)<br>|
| Placebo Comparator: Placebo arm<br>Subjects will take active vitamin daily for 6 months | Dietary Supplement: Active placebo<br>* Active placebo contains active vitamin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alleviation of symptoms or complications | Proportion of subjects with alleviation of symptoms or complication of post-COVID conditions within 6 months. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Any comorbidities | A composite outcome of any comorbidities, including clinical manifestations of long-COVID, hospitalizations due to sepsis, cardiopulmonary complications, metabolic syndrome and neuropsychiatric disorders | 24 months | 
| Increase in metabolic syndrome (MetS) score | a validated index computed from an analysis based on waist circumference, fasting triglycerides, fasting glucose, and systolic blood pressure, calculated in score (1-5), higher levels indicated higher probability of presence of metabolic syndrome | 24 months | 
| Increase in other system-specific comorbidities | Increase in other system-specific comorbidities involving cardiovascular, gastrointestinal, liver, renal, genitourinary, haematological, and neurological systems | 24 months | 
| Healthcare service utilization | The frequency of healthcare service (including clinics and Accident and Emergency) that the subject has attended | 24 months | 
| Self-reported long-COVID-19 symptoms | Subjects will fill in a survey whether they have long-COVID-19 symptoms (e.g. cough, fatigue, etc) and grade the symptoms. The higher the score, the worse the outcome. | 24 months | 
| Changes in Quality of life | Changes in Quality of life using visual analogue scale, score ranging 0-100. The higher the score, the better the outcome. | 48 months | 
| Changes in faecal microbial and bacterial metabolites | Shotgun metagenomics and metabolomics sequencing of faecal samples at baseline and each visit will be used to generate serial gut microbial taxonomic and bacterial functional profiles. | 48 months | 
| Blood immunity profiles | Inflammatory cytokines in plasma samples will be identified and quantified using human inflammation panel 1 (13-plex) of LEGENDplex | 24 months |