Low-field Magnetic Resonance Imaging in Pediatric Post 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. These viruses predominantly cause mild colds, but can sometimes cause severe pneumonia and pulmonary skeletal changes. By low-field gastric magnetic resonance imaging (NF-MRI), only a small number of structural, scarring changes were seen in a preliminary study of pediatric and adolescent patients with past SARS-CoV-2 infection. In contrast, however, extensive changes in ventilation and blood flow function of the lungs were seen. The long-term consequences and spontaneous progression of these changes on imaging are completely unclear. The aim of this study is to assess the course of these functional lung changes in pediatric and adolescent patients and to validate them with other standard clinical procedures.

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 and pulmonary skeletal disease. While the molecular basis for the changes in lung tissue or multi-organ involvement have been described, the age-specific long-term consequences, especially in children and adolescents, remain largely unexplained and misunderstood today. 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 as well as 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 aperture (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 broad pediatric population without the need for sedation. To date, no structural changes were revealed by means of this MRI technique - however, large defects in the area of ventilation and blood flow function of the lung are apparent in specific functional sequences. The aim of this study is to assess the course of these functional lung changes in pediatric and adolescent patients and to validate them with other standard clinical procedures.

Official Title
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Low-field Magnetic Resonance Imaging to Assess Changes in Pulmonary Function Parameters in Confirmed Pediatric SARS-CoV-2 Infection

Conditions
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COVID-19, COVID-19 Respiratory Infection, Long COVID

Intervention / Treatment
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* Diagnostic Test: Low-field magnetic resonance imaging
* Diagnostic Test: Nailfold capillaroscopy
* Diagnostic Test: Spiroergometry
* Diagnostic Test: Realtime deformability cytometry


Participation Criteria
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Eligibility Criteria
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Control arm: Inclusion Criteria: Proof of SARS-CoV-2 infection and at least 2/3 times complete vaccination before infection (at least 14 days) (complete vaccination status according to German recommendations) Long Covid criteria not met according to AWMF S1 guideline Exclusion Criteria: Acute SARS-CoV-2 infection and need for isolation Necessary quarantine Pregnancy, lactation Indication of acute infection Known pleural or pericardial effusion Critical condition (need for respiratory support, ventilation, oxygen administration, shock, symptomatic heart failure) Marked thoracic deformities Previous lung surgery Injuries that do not allow for physical stress testing Refusal of MRI imaging General contraindications to MRI examinations (e.g., electrical implants such as pacemakers or perfusion pumps, etc.) History, clinical, or other suspicion of pulmonary disease Current respiratory infection/symptomatology Pain leading to respiratory limitation Inhaled therapy (e.g., steroids or beta-mimetics) Immunosuppression Any condition that may lead to respiratory limitation (e.g., pain disorder) Obesity (>97% of age percentile) Recovered arm: Inclusion Criteria: Positive SARS-CoV-2 infection confirmed by PCR Long Covid criteria not met according to AWMF S1 guideline Exclusion Criteria: Acute SARS-CoV-2 infection and need for isolation Necessary quarantine Pregnancy, lactation Indication of acute infection Known pleural or pericardial effusion Critical condition (need for respiratory support, ventilation, oxygen administration, shock, symptomatic heart failure) Marked thoracic deformities Previous lung surgery Injuries that do not allow for physical stress testing Refusal of MRI imaging General contraindications to MRI examinations (e.g., electrical implants such as pacemakers or perfusion pumps, etc.) Long Covid arm: Inclusion Criteria: Positive SARS-CoV-2 infection confirmed by PCR Long Covid criteria according to AWMF S1 guideline fulfilled Exclusion Criteria: Acute SARS-CoV-2 infection and need for isolation Necessary quarantine Pregnancy, lactation Indication of acute infection Known pleural or pericardial effusion Critical condition (need for respiratory support, ventilation, oxygen administration, shock, symptomatic heart failure) Marked thoracic deformities Previous lung surgery Injuries that do not allow for physical stress testing Refusal of MRI imaging General contraindications to MRI examinations (e.g., electrical implants such as pacemakers or perfusion pumps, etc.)

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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 |
| --- | --- |
| Active Comparator: Control<br>Proof of SARS-CoV-2 infection and at least 2/3 times complete vaccination before infection (at least 14 days) (complete vaccination status according to STIKO, German vaccination committee) | Diagnostic Test: Low-field magnetic resonance imaging<br>* Functional and morphologic imaging of the lungs<br>* Other names: LF-MRI;Diagnostic Test: Nailfold capillaroscopy<br>* Imaging of nailfold microvasculature<br>Diagnostic Test: Spiroergometry<br>* Cardiopulmonary exercise testing<br>Diagnostic Test: Realtime deformability cytometry<br>* High-throughput measurement of cell deformability and physical properties<br>* Other names: RT-DC;|
| Active Comparator: Recovered<br>Positive SARS-CoV-2 infection confirmed by PCR; Long Covid criteria according to AWMF S1 guideline not fulfilled. | Diagnostic Test: Low-field magnetic resonance imaging<br>* Functional and morphologic imaging of the lungs<br>* Other names: LF-MRI;Diagnostic Test: Nailfold capillaroscopy<br>* Imaging of nailfold microvasculature<br>Diagnostic Test: Spiroergometry<br>* Cardiopulmonary exercise testing<br>Diagnostic Test: Realtime deformability cytometry<br>* High-throughput measurement of cell deformability and physical properties<br>* Other names: RT-DC;|
| Experimental: Long Covid<br>Positive SARS-CoV-2 infection confirmed by PCR; Long Covid criteria according to AWMF S1 guideline fulfilled. | Diagnostic Test: Low-field magnetic resonance imaging<br>* Functional and morphologic imaging of the lungs<br>* Other names: LF-MRI;Diagnostic Test: Nailfold capillaroscopy<br>* Imaging of nailfold microvasculature<br>Diagnostic Test: Spiroergometry<br>* Cardiopulmonary exercise testing<br>Diagnostic Test: Realtime deformability cytometry<br>* High-throughput measurement of cell deformability and physical properties<br>* Other names: RT-DC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional lung assessment (LF-MRI) | Change in functional lung parameters | Baseline compared to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morphologic lung assessment (LF-MRI) | Morphologic changes in lung parenchyma | Baseline compared to 6 months | 
| Cardiological functional diagnostics (VO2) | Oxygen uptake (VO2) | Baseline compared to 6 months | 
| Cardiological functional diagnostics (VO2max) | Peak oxygen uptake (VO2max) | Baseline compared to 6 months | 
| Cardiological functional diagnostics (VT2) | Ventilatory anaerobic threshold (VT2) | Baseline compared to 6 months | 
| Cardiological functional diagnostics (VCO2) | Carbon dioxide output (VCO2) | Baseline compared to 6 months | 
| Cardiological functional diagnostics (HR) | Heart rate (HR) | Baseline compared to 6 months | 
| Cardiological functional diagnostics (HRR) | Heart Rate Reserve (HRR) | Baseline compared to 6 months | 
| Cardiological functional diagnostics (Breath rate at VAT) | Breath rate at VAT | Baseline compared to 6 months | 
| Cardiological functional diagnostics (BRR) | Breath rate reserve (BRR) | Baseline compared to 6 months | 
| Cardiological functional diagnostics (VE) | Minute ventilation (VE) | Baseline compared to 6 months | 
| Cardiological functional diagnostics (O2Pulse) | O2Pulse | Baseline compared to 6 months | 
| Cardiological functional diagnostics (HRV) | Heart rate variability (HRV) | Baseline compared to 6 months | 
| Cardiological functional diagnostics (Borg Scale) | Exercise capacity nach Borg Scale | Baseline compared to 6 months | 
| Cardiological functional diagnostics (BGA) | Capillary blood gas and lactate (BGA) | Baseline compared to 6 months | 
| Nailfold capillaroscopy (capillaries) | Number of capillaries in first row | Baseline compared to 6 months | 
| Nailfold capillaroscopy (first row) | Number of capillaries in first row | Baseline compared to 6 months | 
| Nailfold capillaroscopy (morphology) | Morphology of capillaries | Baseline compared to 6 months | 
| Blood sample (antibodies) | SARS-CoV2-antibodies | Baseline compared to 6 months | 
| Blood sample (auto antibodies) | Autoantibodies against G-protein receptors | Baseline compared to 6 months | 
| Blood sample (RT-DC) | Realtime deformability cytometry | Baseline compared to 6 months | 
| Blood sample (Blood count) | Blood count | Baseline compared to 6 months | 
| Blood sample (IL-6) | Interleukin-6 (IL-6) | Baseline compared to 6 months | 
| Blood sample (CrP) | C-reactive proteine (CrP) | Baseline compared to 6 months | 
| Blood sample (Calpro) | Calprotectin (Calpro) | Baseline compared to 6 months | 
| Blood sample (Coagulation) | Coagulation factors (Coagulation) | Baseline compared to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Long COVID, post COVID