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

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Dietary supplement: L. reuteri DSM 17938 + vitamin D; Dietary supplement: Placebo + vitamin D

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 161
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Örebro Län
    • Örebro, Örebro Län, Sweden, 703 62
      • Örebro University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent
2. Age between 18-60

Exclusion Criteria:

1. Previous diagnosis of COVID-19 (by positive PCR) or previous confirmation of seropositivity to SARS-CoV-2
2. Body Mass Index over 35 or under 16
3. Current diagnosis of cancer or ongoing cancer treatment in the last 12 months
4. Diabetes mellitus
5. Cardiovascular disorder in need of pharmaceutical treatment
6. Chronic kidney disease
7. Chronic lung disease with decreased lung capacity
8. Chronic liver disease with liver cirrhosis
9. Current diagnosis of dementia, severe depression, major psychiatric disorder, or other incapacity for adequate cooperation
10. Chronic neurological/neurodegenerative disease (e.g. Parkinson's disease)
11. Decreased function of the adrenal cortex (e.g. Addison's disease)
12. Autoimmune disease (e.g. rheumatoid arthritis)
13. Chronic pain syndromes (e.g. fibromyalgia)
14. Pregnancy or breast-feeding
15. Immunodeficiency due to disease or ongoing medical treatment
16. Regular intake of anti-inflammatory and/or other immunosuppressive medication within the last 3 months
17. Use of anti-depressants within the last 3 months
18. Antimicrobial treatment within the last 12 weeks before baseline sampling
19. 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
20. Inability to maintain current diet and lifestyle during the study period
21. Alcohol or drug abuse
22. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: L. reuteri DSM 17938; Probiotic compound	Dietary supplement: L. reuteri DSM 17938 + vitamin D; 1 * 10^8 CFU of L. reuteri DSM 17938 + 10 ug vitamin D3, two capsules per day for 6 months
Placebo Comparator: Placebo; Placebo compound	Dietary supplement: Placebo + vitamin D; 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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composition of intestinal microbiota and COVID-19 related symptoms	Correlation of intestinal microbiota composition to duration and severity of COVID-19 related symptoms	3 months + 6 months
Composition of intestinal microbiota and SARS-CoV-2 specific antibody	Correlation of intestinal microbiota composition to SARS-CoV-2 specific antibody levels in serum	3 months + 6 months
Composition of intestinal microbiota and inflammatory profile	Correlation of intestinal microbiota composition to TNF-a, IFN-y, IL-1B, IL-4, IL-6, IL-8, IL-10 levels in serum	3 months + 6 months

Collaborators and Investigators

• Sponsor: Örebro University, Sweden
• Collaborators: BioGaia AB

Publications and helpful links

General Publications

• Lehtoranta L, Pitkaranta A, Korpela R. Probiotics in respiratory virus infections. Eur J Clin Microbiol Infect Dis. 2014 Aug;33(8):1289-302. doi: 10.1007/s10096-014-2086-y. Epub 2014 Mar 18.
• Zimmermann P, Curtis N. The influence of probiotics on vaccine responses - A systematic review. Vaccine. 2018 Jan 4;36(2):207-213. doi: 10.1016/j.vaccine.2017.08.069. Epub 2017 Sep 18.

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2020
• Primary Completion (Actual): September 13, 2021
• Study Completion (Actual): September 13, 2021

Study Registration Dates

• First Submitted: December 10, 2020
• First Submitted That Met QC Criteria: January 30, 2021
• First Posted (Actual): February 2, 2021

Study Record Updates

• Last Update Posted (Actual): October 15, 2021
• Last Update Submitted That Met QC Criteria: October 14, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: Provid

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: IPD will not be shared, results will shared only on group-level

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No