The Roles of Vitamin D and Microbiome in Children With Post-acute COVID-19 Syndromes (PACS) and Long COVID

Sponsor

China Medical University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05633472

Collaborator

(none)

150

Enrollment

Location

Arms

35.4

Anticipated Duration (Months)

4.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A double-blind study to evaluate the role of human microbiome and vitamin D in the development of long COVID and PACS in children.

Condition or Disease	Intervention/Treatment	Phase
Post-acute COVID-19 Syndromes	Other: Vitamin D Other: Placebo	N/A

Detailed Description

Children worldwide are at risk of SARS-CoV-2 infection because of a lack of approved vaccines for children aged 0-4 years. Moreover, SARS-CoV-2 infected children also suffered with long term sequels of virus infection, which involved multiple organs, such as fatigue, post-exercise malaise, skeletal muscular pains, headache, palpitation and insomnia. In fact, there is limited evidence available on the long-term impact of SARS-CoV-2 infection in children. Recent studies have shown critical-ill COVID-19 patients suffered with low vitamin D concentration and microbiome dysbiosis in their respiratory and gastrointestinal system. Vitamin D has been known to counteract several respiratory virus infections as well as beneficial functions in multiple organs. Also, commensal microbiota in lung and intestinal tracts exert protective functions against virus infections and, through its metabolite and axis links, has anti-inflammatory actions and homeostasis in multiple organs. Hence, in this study, the investigators hypothesis that long COVID or post-acute COVID syndrome (PACS) in children is due to the effect of post-virus infection on the immuno-metabolism change (vitamin D deficiency) and perturbation of gut microbiota (microbiome dysbiosis), therefore our study aims are first, make the comparisons of vitamin D levels and respiratory and gut microbiome between symptomatic and non-symptomatic post-COVID children using cross-sectional study. Next, for interventional study, patients will be divided in two groups to receive supplementation of vitamin D or placebo for 6 months to evaluate the effect of vitamin D on the symptoms relieve and improvement of microbiome dysbiosis in post-acute COVID syndrome (PACS) children. The investigators expect through this study, the investigators can learn more on the pathogenesis and the effect of vitamin D and microbiota in long COVID and PACS in children.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

The Roles of Vitamin D and Microbiome in Children With Post-acute COVID-19 Syndromes (PACS) and Long COVID

Actual Study Start Date :

Oct 18, 2022

Anticipated Primary Completion Date :

Sep 30, 2025

Anticipated Study Completion Date :

Sep 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental: Treatment group Vitamin D (2000IU/day) for 6 months	Other: Vitamin D Vitamin D (2000IU/day) for 6 months
Placebo Comparator: Placebo Comparator: Control group placebo	Other: Placebo Placebo

Arm

Intervention/Treatment

Experimental: Experimental: Treatment group

Vitamin D (2000IU/day) for 6 months

Other: Vitamin D

Vitamin D (2000IU/day) for 6 months

Placebo Comparator: Placebo Comparator: Control group

placebo

Other: Placebo

Placebo

Outcome Measures

Primary Outcome Measures

Levels of vitamin D [Month 0]
Vitamin D will be measured in a blood sample by ELISA to determine baseline status.
Levels of vitamin D [Month 6]
Vitamin D will be measured in a blood sample to follow the change from baseline in vitamin D level at month 6.
Single nucleotide polymorphism of vitamin D receptor and vitamin D binding protein [Month 0]
Single nucleotide polymorphism (SNP) genotyping will be performed in a blood sample by using TaqMan SNP genotyping assays.
Microbiome [Month 0]
Nasal and anal swabs will be used to detect respiratory and intestinal microbiome by using 16S rRNA sequencing to determine baseline status.
Microbiome [Month 6]
Nasal and anal swabs will be used to detect respiratory and intestinal microbiome by using 16S rRNA sequencing,and to follow the change from baseline in microbiome at month 6.
Total immunoglobulin E (IgE) [Month 0]
Plasma total IgE concentration will be measured by microparticle immunoassay (IMx analyzer, Abbott Laboratories, Abbott Park, IL) and ELISA to determine baseline status.
Total immunoglobulin E (IgE) [Month 6]
Plasma total IgE concentration will be measured by microparticle immunoassay (IMx analyzer, Abbott Laboratories, Abbott Park, IL) and ELISA to follow the change from baseline in total IgE at month 6.
Allergen-specific immunoglobulin E (IgE) [Month 0]
Plasma allergen-specific IgE will be measured by BioIC ®.

Secondary Outcome Measures

Children's Somatic Symptoms Inventory (CSSI) [Month 0 to Month 6]
CSSI. Range (0-4); lower scores indicate better health
KINDL questionnaire [Month 0 to Month 6]
For assessing Health-Related Quality of Life in children and adolescents aged 3 years and older.

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Children aged 0-18 years
The child sought/needed primary or secondary medical care for COVID-19
Laboratory (RT-PCR, COVID-19 antigen tests or SARS-CoV-2 antibody testing) or physician confirmed SARS-CoV-2 infection based on classic clinical symptoms and/or ground-glass opacification on CT imaging.
28 days - 3 months from the onset of COVID-19 symptoms
Parent's/carer's/guardians consent to participate

Exclusion Criteria:

Recruit patients who have used antibiotics, systemic steroids, and immunosuppressants in the previous month.
Patients with C1 esterase inhibitor deficiency, lymphocytopenia, thrombocytopenia, severe diseases involving heart, liver, or kidney, metabolic disease, or autoimmune disease.