The Effect of Probiotic Supplementation on SARS-CoV-2 Antibody Response After COVID-19

Study Overview
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Brief Summary
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This study will explore how a well-known probiotic strain L. reuteri DSM 17938 impacts SARS-CoV-2 specific antibody response upon and after infection in healthy adults.

Detailed Description
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After giving their informed consent, the study subjects will complete screening procedures to assess their eligibility for the study (Visit 1). Participants deemed suitable for the study will be randomized into two study arms (placebo, probiotic) before undergoing a baseline visit (Visit 2) before the start of the intervention period. During the 6-month intervention period, the participants will attend study visits at 3 months (Visit 3) into the intervention as well as at the end of intervention (at 6 months, Visit 4). Blood, saliva, and faecal samples will be collected at visits 2-4. In addition to sampling, during the whole intervention period, the participants will fill out a weekly questionnaire in which they are asked to record any possible symptoms of COVID-19. The participants' dietary habits are assessed via a food frequency questionnaire (FFQ) before the start of the intervention period. Also, the participants are asked to maintain their habitual diet and lifestyle as well as not to consume any other probiotic or prebiotic supplements.

Official Title
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Exploratory Study on the Effects of Probiotic Supplementation on SARS-CoV-2 Antibody Response in Healthy Adults

Conditions
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Covid19

Intervention / Treatment
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* Dietary Supplement: L. reuteri DSM 17938 + vitamin D
* Dietary Supplement: Placebo + vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Age between 18-60 Exclusion Criteria: Previous diagnosis of COVID-19 (by positive PCR) or previous confirmation of seropositivity to SARS-CoV-2 Body Mass Index over 35 or under 16 Current diagnosis of cancer or ongoing cancer treatment in the last 12 months Diabetes mellitus Cardiovascular disorder in need of pharmaceutical treatment Chronic kidney disease Chronic lung disease with decreased lung capacity Chronic liver disease with liver cirrhosis Current diagnosis of dementia, severe depression, major psychiatric disorder, or other incapacity for adequate cooperation Chronic neurological/neurodegenerative disease (e.g. Parkinson's disease) Decreased function of the adrenal cortex (e.g. Addison's disease) Autoimmune disease (e.g. rheumatoid arthritis) Chronic pain syndromes (e.g. fibromyalgia) Pregnancy or breast-feeding Immunodeficiency due to disease or ongoing medical treatment Regular intake of anti-inflammatory and/or other immunosuppressive medication within the last 3 months Use of anti-depressants within the last 3 months Antimicrobial treatment within the last 12 weeks before baseline sampling Regular intake of probiotics, as well as nutritional supplements or herb products that might affect intestinal function within the last 4 weeks if the investigator considers that those could affect study outcome Inability to maintain current diet and lifestyle during the study period Alcohol or drug abuse Any clinically significant present or past disease/condition which the investigator considers to possibly interfere with the study outcome or increase the risk for severe form of COVID-19

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: L. reuteri DSM 17938<br>Probiotic compound | Dietary Supplement: L. reuteri DSM 17938 + vitamin D<br>* 1 * 10^8 CFU of L. reuteri DSM 17938 + 10 ug vitamin D3, two capsules per day for 6 months<br>|
| Placebo Comparator: Placebo<br>Placebo compound | Dietary Supplement: Placebo + vitamin D<br>* Placebo tablet + 10 ug vitamin D3, Similar in shape and taste to intervention capsules but without the probiotic components, two capsules per day over six weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SARS-CoV-2 specific antibodies | Change in SARS-CoV-2 specific IgG/IgM antibodies in serum between the study arms | 3 months (interim analysis) or at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maintenance of SARS-CoV-2 seroconversion in seropositive individuals | Change in the maintenance of SARS-CoV-2 specific IgG/IgM antibody levels in serum between the study arms | 3 months + 6 months | 
| Duration of COVID-19 symptoms measured by a weekly symptom questionnaire | Change in duration of COVID-19 related symptoms between the study arms | 3 months + 6 months | 
| Severity of COVID-19 symptoms measured by Ordinal Scale for Clinical Improvement (scale 0-7, a lower score corresponds to a better outcome) | Change in severity of COVID-19 related symptoms between the study arms | 3 months + 6 months | 
| Secretory IgA (sIgA) antibodies | Change in sIgA levels in saliva between the study arms | 3 months + 6 months | 
| Blood group A antigen antibodies | Change in anti-A levels in serum between the study arms | 3 months + 6 months | 
| Blood group B antigen antibodies | Change in anti-B levels in serum between the study arms | 3 months + 6 months | 
| Tn antigen antibodies | Change in anti-Tn levels in serum between the study arms | 3 months + 6 months | 
| Innate immune system activation | Change in high-sensitive C-reactive protein (hs-CRP) levels in plasma between the study groups | 3 months + 6 months | 
| Cytokines | Change in TNF-a, IFN-y, IL-1B, IL-4, IL-6, IL-8, IL-10 levels in serum between the study groups | 3 months + 6 months | 
| Total antibodies | Change in total IgG and IgM levels in serum between the study groups | 3 months + 6 months | 
| T cell activation | Change in the proportion of SARS-CoV-2 specific T cells of all T cells in blood between the study arms | 3 months + 6 months | 
| B cell activation | Change in the proportion of SARS-CoV-2 specific B cells of all B cells in blood between the study arms | 3 months + 6 months | 
| Intestinal inflammation | Change in faecal calprotectin levels between the study arms | 3 months + 6 months | 
| Intestinal barrier function | Change in I-FABP levels in plasma between the study arms | 3 months + 6 months | 
| Indirect marker of intestinal permeability | Change in LBP levels in plasma between the study arms | 3 months + 6 months |