Adolescents With COVID-19/MIS-C at HCFMUSP
- Conditions
- SARS (Severe Acute Respiratory Syndrome)Corona Virus InfectionSARS-CoV InfectionCovid19
- Interventions
- Behavioral: Home-based exercise training
- Registration Number
- NCT04659486
- Lead Sponsor
- University of Sao Paulo
- Brief Summary
This is a protocol aimed at children and adolescents contaminated with COVID, treated at the Hospital das Clínicas, University of Sao Paulo, Brazil (HCFMUSP), in the recovery phase. The study aims to evaluate the spectrum of pathogenic lesions of the virus not only in the respiratory system, but digestive, immunological, neurological and others. Clinical, evolutionary, laboratory and functional parameters will be used.
- Detailed Description
School-age children and adolescents COVID-19 survivors may have persistent inflammation, a chronic course of COVID-19, with isolated or concomitant aggressions of various organs and systems, making this disease a potential chronic condition, impacting aspects of quality of life related to health (HRQoL), physical and mental health. In addition, pediatric COVID-19 can induce autoimmunity (with the possibility of primary hypothyroidism and type I diabetes mellitus), delayed linear growth and delayed pubertal development, secondary immunodeficiency and present genetic polymorphisms in brain plasticity impacting rehabilitation. School-aged children and adolescents with COVID-19 could present muscle weakness, dysautonomy, asthenia and physical inactivity, so it is essential that safe and effective interventions are developed to maintain adequate levels of physical activity and that they can be implemented on a large scale. However, to date, there are no systematic longitudinal studies that have evaluated all these aspects in a pediatric population that survived COVID-19, particularly with chronic conditions and who were hospitalized in a tertiary service.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 100
- school-age children and adolescents diagnosed with COVID-19
- school-age children and adolescents with MIS-C, who present: myocardial dysfunction, refractory cardiac arrhythmias, coronary artery aneurysms with or without thrombi, electrocardiographic alterations suggestive of myocardial infarction or ischemia and clinical signs of heart failure;
- presence of any limitation or physical disability that prevents the practice of exercise;
- pregnancy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Exercise training Home-based exercise training A 12 weeks parallel-group randomized controlled trial will be performed, in which covid-19 survivors adolescents will complete a telemonitored home-based exercise training program, 3 times per week. The training program will involve strength and aerobic exercises
- Primary Outcome Measures
Name Time Method Quality of Life assessed by the Pediatric Quality of Life Inventory (Peds-QoL) Change from Baseline at 6 months The instrument was translated and validated for the Brazilian population
- Secondary Outcome Measures
Name Time Method Lactate dehydrogenase Baseline, 3 months, 6 months, 12 months Health-related quality of life assessed by the Pediatric Outcomes Data Collection Instrument Baseline, 3 months, 6 months, 12 months It will also be assessed for school-age children (7-10 years old) and adolescents (11-18 years old) and by their primary caregiver
Inflammatory markers (C-reactive protein, fibrinogen, D-dimer and ferritin); Baseline, 3 months, 6 months,12 months Flow-volume loop assessed by spirometry Baseline, 3 months, 6 months Aims to investigate the mechanisms that lead to dyspnea and, consequently, intolerance to physical effort
Serum urea and creatinine Baseline, 3 months, 6 months, 12 months Pro-BNP Baseline, 3 months, 6 months, 12 months Lung abnormalities will be assessed by pulmonary computed tomography Baseline, 3 months, 6 months, 12 months Patchy ground-glass opacities, crazy-paving pattern, and localization and pattern of large, confluent or small nodular lesions will be assessed
Aspartate and alanine aminotransferase Baseline, 3 months, 6 months, 12 months Complete blood count (hemoglobin, leukocyte, lymphocyte and platelet count) Baseline, 3 months, 6 months, 12 months Serum levels of anti-Streptococcus pneumoniae IgG antibodies Baseline, 3 months, 6 months, 12 months Diagnosis of thyroid dysfunction will be assessed by thyroid profile (TSH, free T4 and T3) Baseline, 3 months, 6 months, 12 months Triglycerides Baseline, 3 months, 6 months, 12 months Creatinine phosphokinase (CK) Baseline, 3 months, 6 months, 12 months Immunophenotyping of lymphocytes T cell lineages will be evaluated by flow cytometry Baseline, 3 months, 6 months, 12 months T cell lineages: CD3CD4, CD3CD8, naive cells (CD45RA+), memory cells (CD45RA-), effector cells (CD38+HLADR+)
Bone age will be assessed using non-dominant hand and wrist radiography Baseline, 12 months Bone mineral content will be assessed by Bone densitometry (DXA) in the region of the lumbar spine Baseline, 3 months, 6 months, 12 months Bone mineral density will be assessed by Bone densitometry (DXA) in the proximal femur Baseline, 3 months, 6 months, 12 months Amilase Baseline, 3 months, 6 months, 12 months Troponin T Baseline, 3 months, 6 months, 12 months Systolic and diastolic function will be assessed by echocardiogram Baseline, 3 months, 6 months, 12 months Conventional transthoracic echocardiogram with color Doppler to assess systolic and diastolic function
Pericardial effusion will be assessed by echocardiogram Baseline, 3 months, 6 months, 12 months Conventional transthoracic echocardiogram with color Doppler to search for pericardial effusion
Coronary arteries will be assessed by echocardiogram Baseline, 3 months, 6 months, 12 months Conventional transthoracic echocardiogram with color Doppler to search for aspects of the coronary arteries
Immunocompetence, including thymic function Baseline, 3 months, 6 months, 12 months Baseline levels of cytokines IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-y, and IL-17A in serum samples will be tested by flow cytometry using the CBA technique (Cytometric bead array, BD Biosciences)
Lipase Baseline, 3 months, 6 months, 12 months Evaluation of the thymus by the determination of TRECs (Thymic recent emigrant cells or T-cell receptor excision circles) Baseline, 3 months, 6 months, 12 months TRECs evaluate the peripheral function of the thymus from cells that have recently been released, using the RT-PCR technique
Changes in frequency of the autoantibodies of the thyroid gland Baseline, 3 months, 6 months, 12 months (anti-thyroperoxidase antibodies, anti-thyroglobulin)
Changes in frequency of the anti-islet antibody of Langerhans will be assessed using indirect fluorescence Baseline, 3 months, 6 months, 12 months Changes in frequency of the anti-insulin antibody will be assessed by radioimmunoassay Baseline, 3 months, 6 months, 12 months Diagnosis of type 1 diabetes mellitus will be assessed by the metabolic profile (fasting glucose, glycated hemoglobin and C peptide) Baseline, 3 months, 6 months,, 12 months Valve dysfunction will be assessed by echocardiogram Baseline, 3 months, 6 months, 12 months Conventional transthoracic echocardiogram with color Doppler to search for valve dysfunction
Ischemia will be assessed by echocardiogram Baseline, 3 months, 6 months, 12 months Echocardiogram with two-dimensional speckle-tracking technique to identify subclinical changes suggestive of ischemia or myocarditis
Leukogram will be assessed by leukocyte and lymphocyte counts Baseline, 3 months, 6 months,, 12 months Immunophenotyping of lymphocytes B cell lineages will be evaluated by flow cytometry Baseline, 3 months, 6 months, 12 months B cell lineages: CD19, naive cells (CD27-), memory cells (CD27+), plasmablasts (CD27+CD38+CD138-), (plasmocytes CD27+CD38+CD138+)
Immunophenotyping of lymphocytes NK cells will be evaluated by flow cytometry Baseline, 3 months, 6 months, 12 months NK cells: (CD3-CD16+CD56+), degranulated: CD107a+
Changes in frequency of the anti-GAD antibody will be assessed using immunoprecipitation Baseline, 3 months, 6 months, 12 months Linear growth will be assessed by using a standardized stadiometer, calculating standard deviation, growth curves, and growth speed Baseline, 3 months, 6 months, 12 months Bone mineral content will be assessed by Bone densitometry (DXA) in the whole body Baseline, 3 months, 6 months, 12 months Body composition (lean mass) will be assessed by Bone densitometry Baseline, 3 months, 6 months, 12 months Development of puberty will be assessed according to the criteria of Tanner and Marshall in adolescents in the prepubertal age group Baseline, 3 months, 6 months, 12 months Anti-pneumococcal vaccine response will be assessed by ELISA Baseline, 3 months, 6 months, 12 months The antipneumococcal antibody titer against 6 polysaccharides (serotypes 1, 5, 6B, 9V, 14, and 18C) will be analyzed by ELISA. The seroconversion criteria is IgG values \> 1.3 mg/mL for each polysaccharide assessed
Bone mineral content will be assessed by Bone densitometry (DXA) in the proximal femur Baseline, 3 months, 6 months, 12 months Bone mineral density will be assessed by Bone densitometry (DXA) in the whole body Baseline, 3 months, 6 months, 12 months Mental health will be assessed by the "Depression, Anxiety and Stress Scale" Baseline, 3 months, 6 months, 12 months The Depression, Anxiety and Stress Scale - 21 Items (DASS-21) is a set of three self-report scales designed to measure the emotional states of depression, anxiety and stress (7 items each subscale). Patients are asked to score every item on a scale from 0 (did not apply to me at all) to 3 (applied to me very much). Sum scores for the total DASS-total scale range between 0 and 120. Scores ≥60 (for DASS-total) and ≥21 (for the depression subscale) are labeled as "high" or "severe".
Blood flow will be assessed using a Doppler Ultrasound Baseline, 3 months, 6 months, 12 months Baseline blood flow measurements will be assessed in the brachial artery
Bone mineral density will be assessed by Bone densitometry (DXA) in the region of the lumbar spine Baseline, 3 months, 6 months, 12 months Body composition (visceral adipose tissue) will be assessed by Bone densitometry Baseline, 3 months, 6 months, 12 months Pediatric gait assessment will be assessed by an Actigraph (3D accelerometer) model G-Walk during the 6-minute walk test Baseline, 3 months, 6 months, 12 months Pediatric gait assessment will be assessed by an Actigraph (3D accelerometer) model G-Walk during the 10 meter gait test Baseline, 3 months, 6 months, 12 months Pediatric gait assessment will be assessed by musculoskeletal ultrasound Baseline, 3 months, 6 months, 12 months Physical activity levels assessed by ActivPAL Baseline, 3 months, 6 months, 12 months ActivPAL will be used for 7 days for at least 10 hours/day
Endothelial function will be assessed using a Doppler Ultrasound Baseline, 3 months, 6 months, 12 months Flow-mediated vasodilation (VMF) will be assessed in the brachial artery
Food consumption levels assessed by food records Baseline, 3 months, 6 months, 12 months 24-hour recalls will be assessed on three non-consecutive days (two weekdays, and one weekend). Online Dietbox will be used.
Bone biochemical and bone remodeling markers (calcium, phosphorus, 25OH alkaline phosphatase vitamin D, PTH, CTX, P1NP) Baseline, 3 months, 6 months, 12 months Genetic Polymorphism Analysis will be assessed by salting out methodology followed by q-PCR (Real-time PCR) using the TaqMan assay using Step One Plus equipment Baseline, 3 months, 6 months, 12 months According to the gene sequence studied, the analysis will be performed using the Sanger sequencing technique with capillary electrophoresis in a 3130 automatic sequencer (Applied Biosystems).
The genetic polymorphisms of the ABO system gene (rs505922), two polymorphisms of the OPRM1 gene (rs1799971 and rs1799972) and a polymorphism of the BDNF gene (rs6265) will be investigated, with possible contributions to the risk of impaired gait.Mental health will be assessed by the "Strengths and Weaknesses of Attention-deficit/hyperactivity disorder (ADHD) symptoms and Normal behaviors" Baseline, 3 months, 6 months, 12 months This is an 18-item parent questionnaire for children and adolescents (18 years and younger). This rating scale includes positive "weaknesses" and negative "strengths" scoring, assessing symptoms of Attention-Deficit/Hyperactivity Disorder. Parents are asked to compare their child's behavior in a variety of settings over the past month to other children on a 7-point: 3-Far below, 2-Below, 1-Slightly below, 0-Average, -1-Slightly average, -2-Above, -3-Far above. Higher scores indicate greater symptomology
Mental health will be assessed by the "Strengths and Difficulties Questionnaire" Baseline, 3 months, 6 months, 12 months The Strengths and Difficulties Questionnaire (SDQ) is a brief behavioural screening questionnaire, and includes 25 items on psychological attribute: emotional symptoms (5 items), conduct problems (5 items) hyperactivity/inattention (5 items), peer relationship problems (5 items), prosocial behaviour (5 items). Higher scores indicate greater difficulties
Body composition (fat mass) will be assessed by Bone densitometry Baseline, 3 months, 6 months, 12 months Pediatric gait assessment will be assessed by an Actigraph (3D accelerometer) model G-Walk used during the "timed up and go" test Baseline, 3 months, 6 months, 12 months
Trial Locations
- Locations (1)
Hospital das Clinicas Faculdade de Medicina USP
🇧🇷Sao Paulo, SP, Brazil