Low-field Magnetic Resonance Imaging of Pediatric COVID-19

Study Overview
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Brief Summary
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SARS-CoV-2 (Severe acute respiratory syndrome coronavirus type 2) is a new coronavirus and identified causative agent of COVID-19 disease. They predominantly cause mild colds but can sometimes cause severe pneumonia. The long-term consequences are still largely unexplained and misunderstood, especially in children and adolescents. The aim of this study is to assess the frequency of pulmonary skeletal changes in pediatric and adolescent patients using low-field magnetic resonance imaging (LF-MRI) in the setting of proven past SARS-CoV-2 infection.

Detailed Description
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SARS-CoV-2 (Severe acute respiratory syndrome coronavirus type 2) is a new coronavirus and identified causative agent of COVID-19 disease. They predominantly cause mild colds, but can sometimes cause severe pneumonia. While the molecular basis for the changes in lung tissue or multi-organ involvement has been described, the age-specific long-term consequences, especially in children and adolescents, are still largely unexplained and not understood. Early publications from the primarily affected Chinese provinces described rather mild, partly asymptomatic courses in children. This is consistent with the observation that the risk of severe COVID-19 disease increases steeply from the age of 70 years, and is also determined by the severity of obesity and other risk factors. Developmental expression of tissue factors may be one reason for the relative protection of younger patients from severe courses of the disease. However, it is now becoming increasingly clear that some individuals with milder initial symptoms of COVID-19 may suffer from variable and persistent symptoms for many months after initial infection - this includes children. A modern low-field MRI is located in Erlangen, Germany. This technique has already been used to demonstrate persistent damage to lung tissue in adult patients after COVID-19. The device with a field strength of 0.55 Tesla (T) currently has the world's largest bore (and is thus particularly suitable for patients with claustrophobia, among other things), a very quiet operating noise, and lower energy absorption in the tissue due to the weaker magnetic field than MRI scanners with 1.5T or 3T. This allows MRI imaging in a very wide pediatric population without the need for sedation. The purpose of this study is to assess the frequency of lung parenchymal changes using low-field magnetic resonance imaging (LF-MRI) in pediatric and adolescent patients with past SARS-CoV-2 infection detected by PCR.

Official Title
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Low-fielD magnEtiC Resonance Imaging of pulmonarY Parenchyma Changes Associated wiTh Confirmed SARS-CoV-2 Infection in Children and Adolescents

Conditions
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Sars-CoV-2 Infection, Covid19, Lung Fibrosis

Intervention / Treatment
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* Diagnostic Test: Low-field magnetic resonance imaging
* Diagnostic Test: Blood sample


Participation Criteria
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Eligibility Criteria
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Covid-19 group Inclusion Criteria: (Past) Positive SARS-CoV-2 Infection (PCR proven) Age 5 to <18 years Exclusion Criteria: Acute SARS-CoV-2 Infection and Isolation Quarantine Pregnancy Critical Illness No consent to LF_MRI General contraindications for LF-MRI, such as electrical implants, pace makers, perfusion pumps) Healthy controls Inclusion Criteria: - Age 5 to <18 years Exclusion Criteria: (Past) Positive SARS-CoV-2 Infection (PCR or antigen test proven) Suspect for lung disease Acute respiratory infection/symptomatic Acute SARS-CoV-2 Infection and Isolation Quarantine Pregnancy Critical Illness No consent to LF_MRI General contraindications for LF-MRI, such as electrical implants, pace makers, perfusion pumps)

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 18 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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Covid-19 subjects<br>Childrens and adolescent with PCR-proven previous SARS-CoV-2 infection | Diagnostic Test: Low-field magnetic resonance imaging<br>* Imaging of lung parenchyma and function by LF-MRI<br>Diagnostic Test: Blood sample<br>* Blood sample for diagnostic testing<br>|
| Active Comparator: Healthy controls<br>Healthy controls negative for previous SARS-CoV-2 infection | Diagnostic Test: Low-field magnetic resonance imaging<br>* Imaging of lung parenchyma and function by LF-MRI<br>Diagnostic Test: Blood sample<br>* Blood sample for diagnostic testing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Low-field magnetic resonance imaging | Lung parenchymal changes (Ground-glass opacification/opacity (GGO)) | Single time point (1 day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood sample: Serum | Antibodies against SarS-CoV-2 (spike proteine) | Single time point (1 day) | 
| Blood sample: Serum | Antibodies against SarS-CoV-2 (nuceleocapsid) | Single time point (1 day) | 
| Blood sample: Leucocytes | Physical properties of single cells: Deformation | Single time point (1 day) | 
| Blood sample: Leucocytes | Physical properties of single cells: Cells size [µm³] | Single time point (1 day) | 
| Blood sample: Leucocytes | Physical properties of single cells: Youngs modulus [kPa³] | Single time point (1 day) | 
| Blood sample: Erythrocytes | Physical properties of single cells: Deformation | Single time point (1 day) | 
| Blood sample: Erythrocytes | Physical properties of single cells: Cells size [µm³] | Single time point (1 day) | 
| Blood sample: Erythrocytes | Physical properties of single cells: Youngs modulus [kPa³] | Single time point (1 day) | 
| Blood sample: Monocytes | Physical properties of single cells: Deformation | Single time point (1 day) | 
| Blood sample: Monocytes | Physical properties of single cells: Cells size [µm³] | Single time point (1 day) | 
| Blood sample: Monocytes | Physical properties of single cells: Youngs modulus [kPa³] | Single time point (1 day) | 
| Low-field magnetic resonance imaging | Lung functional changes (Ventilation defects) | Single time point (1 day) | 
| Low-field magnetic resonance imaging | Lung functional changes (Perfusion defects) | Single time point (1 day) | 
| Low-field magnetic resonance imaging | Lung functional changes (Combined defects) | Single time point (1 day) | 
| Blood sample: IL-6 | Serum level of IL-6 | Single time point (1 day) | 
| Blood sample: C-reactive protein | Serum level of C-reactive protein | Single time point (1 day) | 
| Blood sample: D-dimers | Serum level of D-dimers | Single time point (1 day) |