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

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

Study Overview

• Status: Recruiting
• Conditions: Post-acute COVID-19 Syndromes
• Intervention / Treatment: Other: Placebo; Other: Vitamin D

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 Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jiu-Yao Wang, MD; Phone Number: 4131 886422052121; Email: aim.cmuh@gmail.com

Study Locations

• Taiwan
  • Taichung, Taiwan, 404
    • Recruiting
    • China Medical University Hospital
    • Contact: Jiu-Yao Wang, MD; Phone Number: 4131 886422052121; Email: aim.cmuh@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Children aged 0-18 years
2. The child sought/needed primary or secondary medical care for COVID-19
3. 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.
4. 28 days - 3 months from the onset of COVID-19 symptoms
5. Parent's/carer's/guardians consent to participate

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: China Medical University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2022
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: November 30, 2022
• First Submitted That Met QC Criteria: November 30, 2022
• First Posted (Actual): December 1, 2022

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Long COVID; vitamin D; human microbiome; Post-acute COVID-19 Syndromes (PACS)
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Disease; Chronic Disease; Post-Infectious Disorders; COVID-19; Syndrome; Post-Acute COVID-19 Syndrome; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: CMUH111-REC2-122

Drug and device information, study documents

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