DECRYPT: Low-field Magnetic Resonance Imaging of Pediatric COVID-19
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. 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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
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. 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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Covid-19 subjects Childrens and adolescent with PCR-proven previous SARS-CoV-2 infection |
Diagnostic Test: Low-field magnetic resonance imaging
Imaging of lung parenchyma and function by LF-MRI
Diagnostic Test: Blood sample
Blood sample for diagnostic testing
|
Active Comparator: Healthy controls Healthy controls negative for previous SARS-CoV-2 infection |
Diagnostic Test: Low-field magnetic resonance imaging
Imaging of lung parenchyma and function by LF-MRI
Diagnostic Test: Blood sample
Blood sample for diagnostic testing
|
Outcome Measures
Primary Outcome Measures
- Low-field magnetic resonance imaging [Single time point (1 day)]
Lung parenchymal changes (Ground-glass opacification/opacity (GGO))
Secondary Outcome Measures
- Blood sample: Serum [Single time point (1 day)]
Antibodies against SarS-CoV-2 (spike proteine)
- Blood sample: Serum [Single time point (1 day)]
Antibodies against SarS-CoV-2 (nuceleocapsid)
- Blood sample: Leucocytes [Single time point (1 day)]
Physical properties of single cells: Deformation
- Blood sample: Leucocytes [Single time point (1 day)]
Physical properties of single cells: Cells size [µm³]
- Blood sample: Leucocytes [Single time point (1 day)]
Physical properties of single cells: Youngs modulus [kPa³]
- Blood sample: Erythrocytes [Single time point (1 day)]
Physical properties of single cells: Deformation
- Blood sample: Erythrocytes [Single time point (1 day)]
Physical properties of single cells: Cells size [µm³]
- Blood sample: Erythrocytes [Single time point (1 day)]
Physical properties of single cells: Youngs modulus [kPa³]
- Blood sample: Monocytes [Single time point (1 day)]
Physical properties of single cells: Deformation
- Blood sample: Monocytes [Single time point (1 day)]
Physical properties of single cells: Cells size [µm³]
- Blood sample: Monocytes [Single time point (1 day)]
Physical properties of single cells: Youngs modulus [kPa³]
- Low-field magnetic resonance imaging [Single time point (1 day)]
Lung functional changes (Ventilation defects)
- Low-field magnetic resonance imaging [Single time point (1 day)]
Lung functional changes (Perfusion defects)
- Low-field magnetic resonance imaging [Single time point (1 day)]
Lung functional changes (Combined defects)
- Blood sample: IL-6 [Single time point (1 day)]
Serum level of IL-6
- Blood sample: C-reactive protein [Single time point (1 day)]
Serum level of C-reactive protein
- Blood sample: D-dimers [Single time point (1 day)]
Serum level of D-dimers
Eligibility Criteria
Criteria
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)
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Department of Pediatrics and Adolescent Medicine | Erlangen | Bavaria | Germany | 91054 |
Sponsors and Collaborators
- University of Erlangen-Nürnberg Medical School
Investigators
- Principal Investigator: Ferdinand Knieling, MD, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen
Study Documents (Full-Text)
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.
- 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.
- 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.
- 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: lung-network@humancellatlas.org; 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.
- 206_21 B