Pulmonary Dysfunction after Pediatric COVID-19

Abstract

Background Long COVID occurs at a lower frequency in children and adolescents than in adults. Morphologic and free-breathing phase-resolved functional low-field-strength MRI may help identify persistent pulmonary manifestations after SARS-CoV-2 infection. Purpose To characterize both morphologic and functional changes of lung parenchyma at low-field-strength MRI in children and adolescents with post-COVID-19 condition compared with healthy controls. Materials and Methods Between August and December 2021, a cross-sectional clinical trial using low-field-strength MRI was performed in children and adolescents from a single academic medical center. The primary outcome was the frequency of morphologic changes at MRI. Secondary outcomes included MRI-derived functional proton ventilation and perfusion parameters. Clinical symptoms, the duration from positive reverse transcriptase-polymerase chain reaction test result, and serologic parameters were compared with imaging results. Nonparametric tests for pairwise and corrected tests for groupwise comparisons were applied to assess differences in healthy controls, recovered participants, and those with long COVID. Results A total of 54 participants after COVID-19 infection (mean age, 11 years ± 3 [SD]; 30 boys [56%]) and nine healthy controls (mean age, 10 years ± 3; seven boys [78%]) were included: 29 (54%) in the COVID-19 group had recovered from infection and 25 (46%) were classified as having long COVID on the day of enrollment. Morphologic abnormality was identified in one recovered participant. Both ventilated and perfused lung parenchyma (ventilation-perfusion [V/Q] match) was higher in healthy controls (81% ± 6.1) compared with the recovered group (62% ± 19; P = .006) and the group with long COVID (60% ± 20; P = .003). V/Q match was lower in patients with time from COVID-19 infection to study participation of less than 180 days (63% ± 20; P = .03), 180-360 days (63% ± 18; P = .03), and 360 days (41% ± 12; P < .001) as compared with the never-infected healthy controls (81% ± 6.1). Conclusion Low-field-strength MRI showed persistent pulmonary dysfunction in children and adolescents who recovered from COVID-19 and those with long COVID. Clinical trial registration no. NCT04990531 © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Paltiel in this issue.

Conflict of interest statement

Disclosures of conflicts of interest: R.H. Member of the Siemens Healthineers speakers bureau. L.T. No relevant relationships. S.S. No relevant relationships. A.P.R. No relevant relationships. F.E. No relevant relationships. D.M. No relevant relationships. A.B. No relevant relationships. J.V.C. No relevant relationships. A.V. Research grant from Siemens Healthineers. M.R. No relevant relationships. O.R. No relevant relationships. A.M.N. Research support from Siemens Healthineers. S.L. No relevant relationships. S.B. Lecture fees from Siemens Healthineers; research coordinator for the Bavarian Digital Health Initiative by the BayFor (Bavarian Research Alliance); research support to institution from Siemens Healthineers. M.S.M. Honoraria for lectures from Siemens Healthineers and Bayer Healthcare. M.U. Member of the Siemens Healthineers speakers bureau. M.M. No relevant relationships. R.T. No relevant relationships. J.W. Consulting fees from Ipsen, Hexal, and Novo Nordisk; honoraria for lectures from Pfizer, Merck Serono, and Novo Nordisk; advisory board membership fees from Ipsen, Hexal, and Novo Nordisk; treasurer and past president of the German Society for Pediatric Endocrinology and board member of patient advocacy group for people with short stature. A.L.W. Research grant from Bayerischen Wissenschaftsministeriums zur Corona-Forschung. F.K. Research grants from Sanofi Genzyme, Else Kröner-Fresenius-Stiftung, IMI J2 EU Horizon 2020, Deutsche Gesellschaft für Ultraschall in der Medizin, Interdisciplinary Center for Clinical Research, UK Erlangen, Bayerische Forschungsstiftung, and the Bavarian Ministry of Health; lecture fees from Sanofi Genzyme and Siemens Healthineers; travel support from iThera Medical; patent for device and method for analyzing optoacoustic data, optoacoustic system, and computer program.

Figures

Graphical abstract

Figure 1:

Flowchart of the study. RT-PCR = reverse transcriptase–polymerase chain reaction.

Figure 2:

Free-breathing phase-resolved functional lung, or PREFUL, low-field-strength MRI at 0.55 T with calculated parameters at the axial plane after automatic registration to a midexpiration position and lung parenchyma segmentation. From left to right, representative color-coded images from functional lung MRI show ventilation defects (blue), perfusion defects (red), ventilation-perfusion (V/Q) match (green), and V/Q defects (purple) in a healthy control participant (upper row, 7-year-old boy), a participant who recovered from COVID-19 (middle row, 10-year-old boy), and a participant with long COVID (bottom row, 15-year-old boy). QDP = perfusion defect percentage, VDP = ventilation defect percentage.

Figure 3:

Dot plots show the comparison of low-field-strength MRI parameters with respect to the interval from first infection. The y-axis shows the fraction of defect or nondefect lung parenchyma on the automated measured axial plane. (A) Ventilation defects,(B) perfusion defects, (C)ventilation-perfusion (V/Q) defects, and (D) V/Q match in healthy controls and in participants at less than 180 days, 180–360 days, and more than 360 days after SARS-CoV-2 infection. Midlines indicate the means, and dots represent a single data point or measurement for one participant. * = P < .05, ** = P < .01, and *** = P < .001.