FASCINATE: Low-field Magnetic Resonance Imaging in Pediatric Post Covid-19

• Sponsor: University of Erlangen-Nürnberg Medical School (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05445531
• Collaborator: (none)
• Enrollment: 111
• Location: 1
• Arms: 3
• Anticipated Duration (Months): 8.7
• Patients Per Site Per Month: 12.7

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19; COVID-19 Respiratory Infection; Long COVID	Diagnostic Test: Low-field magnetic resonance imaging; Diagnostic Test: Nailfold capillaroscopy; Diagnostic Test: Spiroergometry; Diagnostic Test: Realtime deformability cytometry	N/A

Detailed Description

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 111 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Low-field Magnetic Resonance Imaging to Assess Changes in Pulmonary Function Parameters in Confirmed Pediatric SARS-CoV-2 Infection
• Anticipated Study Start Date: Jul 8, 2022
• Anticipated Primary Completion Date: Jan 31, 2023
• Anticipated Study Completion Date: Mar 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control 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; Functional and morphologic imaging of the lungs; Other Names: LF-MRI ; Diagnostic Test: Nailfold capillaroscopy; Imaging of nailfold microvasculature; Diagnostic Test: Spiroergometry; Cardiopulmonary exercise testing; Diagnostic Test: Realtime deformability cytometry; High-throughput measurement of cell deformability and physical properties; Other Names: RT-DC
Active Comparator: Recovered 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; Functional and morphologic imaging of the lungs; Other Names: LF-MRI ; Diagnostic Test: Nailfold capillaroscopy; Imaging of nailfold microvasculature; Diagnostic Test: Spiroergometry; Cardiopulmonary exercise testing; Diagnostic Test: Realtime deformability cytometry; High-throughput measurement of cell deformability and physical properties; Other Names: RT-DC
Experimental: Long Covid Positive SARS-CoV-2 infection confirmed by PCR; Long Covid criteria according to AWMF S1 guideline fulfilled.	Diagnostic Test: Low-field magnetic resonance imaging; Functional and morphologic imaging of the lungs; Other Names: LF-MRI ; Diagnostic Test: Nailfold capillaroscopy; Imaging of nailfold microvasculature; Diagnostic Test: Spiroergometry; Cardiopulmonary exercise testing; Diagnostic Test: Realtime deformability cytometry; High-throughput measurement of cell deformability and physical properties; Other Names: RT-DC

Outcome Measures

Primary Outcome Measures

1. Functional lung assessment (LF-MRI) [Baseline compared to 6 months]

   Change in functional lung parameters

Secondary Outcome Measures

1. Morphologic lung assessment (LF-MRI) [Baseline compared to 6 months]

   Morphologic changes in lung parenchyma

2. Cardiological functional diagnostics (VO2) [Baseline compared to 6 months]

   Oxygen uptake (VO2)

3. Cardiological functional diagnostics (VO2max) [Baseline compared to 6 months]

   Peak oxygen uptake (VO2max)

4. Cardiological functional diagnostics (VT2) [Baseline compared to 6 months]

   Ventilatory anaerobic threshold (VT2)

5. Cardiological functional diagnostics (VCO2) [Baseline compared to 6 months]

   Carbon dioxide output (VCO2)

6. Cardiological functional diagnostics (HR) [Baseline compared to 6 months]

   Heart rate (HR)

7. Cardiological functional diagnostics (HRR) [Baseline compared to 6 months]

   Heart Rate Reserve (HRR)

8. Cardiological functional diagnostics (Breath rate at VAT) [Baseline compared to 6 months]

   Breath rate at VAT

9. Cardiological functional diagnostics (BRR) [Baseline compared to 6 months]

   Breath rate reserve (BRR)

10. Cardiological functional diagnostics (VE) [Baseline compared to 6 months]

    Minute ventilation (VE)

11. Cardiological functional diagnostics (O2Pulse) [Baseline compared to 6 months]

    O2Pulse

12. Cardiological functional diagnostics (HRV) [Baseline compared to 6 months]

    Heart rate variability (HRV)

13. Cardiological functional diagnostics (Borg Scale) [Baseline compared to 6 months]

    Exercise capacity nach Borg Scale

14. Cardiological functional diagnostics (BGA) [Baseline compared to 6 months]

    Capillary blood gas and lactate (BGA)

15. Nailfold capillaroscopy (capillaries) [Baseline compared to 6 months]

    Number of capillaries in first row

16. Nailfold capillaroscopy (first row) [Baseline compared to 6 months]

    Number of capillaries in first row

17. Nailfold capillaroscopy (morphology) [Baseline compared to 6 months]

    Morphology of capillaries

18. Blood sample (antibodies) [Baseline compared to 6 months]

    SARS-CoV2-antibodies

19. Blood sample (auto antibodies) [Baseline compared to 6 months]

    Autoantibodies against G-protein receptors

20. Blood sample (RT-DC) [Baseline compared to 6 months]

    Realtime deformability cytometry

21. Blood sample (Blood count) [Baseline compared to 6 months]

    Blood count

22. Blood sample (IL-6) [Baseline compared to 6 months]

    Interleukin-6 (IL-6)

23. Blood sample (CrP) [Baseline compared to 6 months]

    C-reactive proteine (CrP)

24. Blood sample (Calpro) [Baseline compared to 6 months]

    Calprotectin (Calpro)

25. Blood sample (Coagulation) [Baseline compared to 6 months]

    Coagulation factors (Coagulation)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Erlangen	Erlangen	Bavaria	Germany	91054

Sponsors and Collaborators

• University of Erlangen-Nürnberg Medical School

Investigators

• Principal Investigator: Ferdinand Knieling, MD, University Hospital Erlangen

Study Documents (Full-Text)

None provided.

More Information

Publications

• Brodin P. Immune determinants of COVID-19 disease presentation and severity. Nat Med. 2021 Jan;27(1):28-33. doi: 10.1038/s41591-020-01202-8. Epub 2021 Jan 13.
• Duan YN, Zhu YQ, Tang LL, Qin J. CT features of novel coronavirus pneumonia (COVID-19) in children. Eur Radiol. 2020 Aug;30(8):4427-4433. doi: 10.1007/s00330-020-06860-3. Epub 2020 Apr 14. Review.
• Heiss R, Grodzki DM, Horger W, Uder M, Nagel AM, Bickelhaupt S. High-performance low field MRI enables visualization of persistent pulmonary damage after COVID-19. Magn Reson Imaging. 2021 Feb;76:49-51. doi: 10.1016/j.mri.2020.11.004. Epub 2020 Nov 18.
• Huang J, Hume AJ, Abo KM, Werder RB, Villacorta-Martin C, Alysandratos KD, Beermann ML, Simone-Roach C, Lindstrom-Vautrin J, Olejnik J, Suder EL, Bullitt E, Hinds A, Sharma A, Bosmann M, Wang R, Hawkins F, Burks EJ, Saeed M, Wilson AA, Mühlberger E, Kotton DN. SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response. Cell Stem Cell. 2020 Dec 3;27(6):962-973.e7. doi: 10.1016/j.stem.2020.09.013. Epub 2020 Sep 18.
• Karki R, Sharma BR, Tuladhar S, Williams EP, Zalduondo L, Samir P, Zheng M, Sundaram B, Banoth B, Malireddi RKS, Schreiner P, Neale G, Vogel P, Webby R, Jonsson CB, Kanneganti TD. Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes. Cell. 2021 Jan 7;184(1):149-168.e17. doi: 10.1016/j.cell.2020.11.025. Epub 2020 Nov 19.
• Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, Zhang W, Wang Y, Bao S, Li Y, Wu C, Liu H, Liu D, Shao J, Peng X, Yang Y, Liu Z, Xiang Y, Zhang F, Silva RM, Pinkerton KE, Shen K, Xiao H, Xu S, Wong GWK; Chinese Pediatric Novel Coronavirus Study Team. SARS-CoV-2 Infection in Children. N Engl J Med. 2020 Apr 23;382(17):1663-1665. doi: 10.1056/NEJMc2005073. Epub 2020 Mar 18.
• Sajuthi SP, DeFord P, Li Y, Jackson ND, Montgomery MT, Everman JL, Rios CL, Pruesse E, Nolin JD, Plender EG, Wechsler ME, Mak ACY, Eng C, Salazar S, Medina V, Wohlford EM, Huntsman S, Nickerson DA, Germer S, Zody MC, Abecasis G, Kang HM, Rice KM, Kumar R, Oh S, Rodriguez-Santana J, Burchard EG, Seibold MA. Type 2 and interferon inflammation regulate SARS-CoV-2 entry factor expression in the airway epithelium. Nat Commun. 2020 Oct 12;11(1):5139. doi: 10.1038/s41467-020-18781-2.
• Schuler BA, Habermann AC, Plosa EJ, Taylor CJ, Jetter C, Negretti NM, Kapp ME, Benjamin JT, Gulleman P, Nichols DS, Braunstein LZ, Hackett A, Koval M, Guttentag SH, Blackwell TS, Webber SA, Banovich NE; Vanderbilt COVID-19 Consortium Cohort; Human Cell Atlas Biological Network, Kropski JA, Sucre JM. Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 in lung epithelium. J Clin Invest. 2021 Jan 4;131(1). pii: 140766. doi: 10.1172/JCI140766.
• Shelmerdine SC, Lovrenski J, Caro-Domínguez P, Toso S; Collaborators of the European Society of Paediatric Radiology Cardiothoracic Imaging Taskforce. Coronavirus disease 2019 (COVID-19) in children: a systematic review of imaging findings. Pediatr Radiol. 2020 Aug;50(9):1217-1230. doi: 10.1007/s00247-020-04726-w. Epub 2020 Jun 18.
• Steinberger S, Lin B, Bernheim A, Chung M, Gao Y, Xie Z, Zhao T, Xia J, Mei X, Little BP. CT Features of Coronavirus Disease (COVID-19) in 30 Pediatric Patients. AJR Am J Roentgenol. 2020 Dec;215(6):1303-1311. doi: 10.2214/AJR.20.23145. Epub 2020 May 22.
• Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, Cao Y, Yousif AS, Bals J, Hauser BM, Feldman J, Muus C, Wadsworth MH 2nd, Kazer SW, Hughes TK, Doran B, Gatter GJ, Vukovic M, Taliaferro F, Mead BE, Guo Z, Wang JP, Gras D, Plaisant M, Ansari M, Angelidis I, Adler H, Sucre JMS, Taylor CJ, Lin B, Waghray A, Mitsialis V, Dwyer DF, Buchheit KM, Boyce JA, Barrett NA, Laidlaw TM, Carroll SL, Colonna L, Tkachev V, Peterson CW, Yu A, Zheng HB, Gideon HP, Winchell CG, Lin PL, Bingle CD, Snapper SB, Kropski JA, Theis FJ, Schiller HB, Zaragosi LE, Barbry P, Leslie A, Kiem HP, Flynn JL, Fortune SM, Berger B, Finberg RW, Kean LS, Garber M, Schmidt AG, Lingwood D, Shalek AK, Ordovas-Montanes J; HCA Lung Biological Network. Electronic address: [e-mail]; HCA Lung Biological Network. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell. 2020 May 28;181(5):1016-1035.e19. doi: 10.1016/j.cell.2020.04.035. Epub 2020 Apr 27.

• Responsible Party: University of Erlangen-Nürnberg Medical School
• ClinicalTrials.gov Identifier: NCT05445531
• Other Study ID Numbers: 22-77-Bm
• First Posted: Jul 6, 2022
• Last Update Posted: Jul 6, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Erlangen-Nürnberg Medical School: COVID-19; Long COVID; post COVID
• Additional relevant MeSH terms: Infections; COVID-19; Respiratory Tract Infections

Study Results

No Results Posted as of Jul 6, 2022