Nutrition, Immunity, and Covid-19 in Obese People

Study Overview
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Brief Summary
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The increased risk of transmission of COVID-19 infection causes the incidence of death in health workers to escalate. It requires further research on risk factors and intervention in health worker professionals, especially on immunity factors and nutritional status. Quality of diet and nutrition is very important to support the immune system when infected. Several probiotic strains have been shown to decrease the duration and incidence of diarrhea and respiratory infections, suggesting the Gut-Lung Axis pathway. Some probiotics also improve the balance of diversity in the composition of the gut microbiota and affect body weight in obese people. Probiotics have also been shown to improve vitamin D absorption. A combination of vitamin D and probiotics may be an alternative to reduce gut dysbiosis that will directly or indirectly reduce the risk and severity of viral infections including SARS-CoV-2.

Detailed Description
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Obesity is increasing in Indonesia and is the cause of various diseases, especially in the presence of Vitamin D deficiency, a state of dysbiosis, causing an increase in the possibility of infection. Professional health workers have a high risk of COVID-19 due to high daily exposure. Based on a review conducted by Daniel et al, it was found that 7.3% of health workers at Reutters University tested positive for COVID-19. Based on data from the Indonesian Doctors Association (IDI) on July 12, 2020, it was known that 61 doctors had died. In addition, based on data from the Indonesian National Nurses Association (PPNI), 39 nurses have died during the COVID-19 pandemic. Therefore efforts to prevent the occurrence of COVID-19 infection by providing a combination of vitamin D and probiotics to modulate dysbiosis that will further reduce the risk of viral infection, especially COVID-19, needs to be investigated for its potential benefits. Primary and secondary objectives Primary Objective: To investigate the effect of a combination of probiotics and vitamin D supplementation in modulating intestinal dysbiosis, and vitamin D status, in people with overweight and obesity, especially among frontline health workers. To assess the mean changes in zonulin levels (as a parameter of gut integrity to indicate the intestinal microbiota dysbiosis) To assess the mean changes in serum vitamin D levels Secondary Objectives: To assess the relationship between nutritional status, inflammation and immunity with the risk of COVID-19 infection in health workers. To understand the difference in the mean episodes of Covid-19 infection between treatment and placebo groups after giving probiotics and vitamin D in people with overweight and obesity, especially among frontline health workers. Study Design: This study has 2 phases Phase 1: a Cross-sectional study with 160 people Phase 2: a double-blind, randomized, placebo-controlled trial with two arms of intervention involving a total of 80 people.

Official Title
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Effect of Probiotic and Vitamin D Supplementation in Modulating Gut Dysbiosis, Nutrition, Inflammation and Immune Status and Reduce Risk of COVID-19 in Obese People: Gut-Lung Axis Randomized Trial

Conditions
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Vitamin D Deficiency, Covid19, Overweight and Obesity, Immune Deficiency

Intervention / Treatment
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* Dietary Supplement: Probiotics, Vitamin D
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General doctors, specialist doctors, nurses and midwives who are in charge of handling COVID-19 patients or working in COVID-19 referral hospitals for at least the last 3 months 20-65 years old Willing to sign informed consent Willing to follow the research to completion BMI > 23 kg/m2 Exclusion Criteria: Pregnant woman Have a confirmed history of COVID-19 based on previous PCR examinations Suffering from acute illness known from history and physical examination or chronic disease (eg diabetes, SLE, cardiovascular disease) known from history Currently not on a diet program for weight loss or consuming probiotics regularly in the last 3 months as known from the anamnesis

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>Probiotics and Vitamin D | Dietary Supplement: Probiotics, Vitamin D<br>* Combination of two supplement that given separately<br>|
| Placebo Comparator: Control Group<br>Placebo and placebo | Other: Placebo<br>* Placebo with inactive ingredient<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Zonulin level | To investigate the changes of Zonulin level during intervention | Baseline and endline (3 month) | 
| Vitamin D level | To investigate the changes of Vitamin D level during intervention | Baseline and endline (3 month) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nutritional status | Measurement of nutritional status using Body Mass Index (BMI) and waist circumference | Baseline and endline (3 month) | 
| Gut microbiota (optional) | Measurement of gut microbiota in fecal using Next Generation Sequencing | Baseline and endline (3 month) | 
| Inflammation marker | Measurement of inflammation markers IL-6, IL-10 TNF-α using ELISA | Screening | 
| Cathelicidin level | Measurement of cathelicidin using ELISA | Screening | 
| SARS COV-2 | Measurement of quantitative antibody | Screening | 
| CD4/CD8 ratio | Measurement of CD4/CD8 ratio using flowcytometry | Screening | 
| Covid-19 infection | Measurement of the reduction in risk of COVID-19 infection is seen from the difference in the average episodes between groups that were examined by PCR and/or Rapid antibody tests. | Baseline and endline (3 month) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Probiotics, Vitamin D, Immune status, Covid-19, Nutrition