Post-COVID-19 condition or syndrome, defined as persistent symptoms that continue for more than 12 weeks following the initial infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can affect individuals of all ages. A less severe variant is usually seen in children and adolescents, but persistent cardiopulmonary symptoms, such as chronic fatigue, dyspnea, headache, and cardiac palpitations, are common in these age groups. In this study, the authors from Germany used phase-resolved functional lung (PREFUL) magnetic resonance imaging (MRI) to investigate pulmonary dysfunction in pediatric post-COVID syndrome. The authors postulated that the lung function of children and adolescents with post-COVID syndrome is different from that of healthy children and that PREFUL MRI characteristics are correlated with the clinical manifestations of post-COVID syndrome.
Previous pulmonary imaging studies with dynamic contrast-enhanced MRI or computerized tomography (CT) in adults with post-COVID syndrome identified various perfusion alterations. Because of radiation exposure and the necessity for an intravenous contrast agent, CT is not used as a standard diagnostic tool in children suspected of having post-COVID syndrome. Therefore, the objective measures available for assessing pulmonary alterations in cases of pediatric post-COVID syndrome are limited. Phase-resolved functional lung (PREFUL) MRI is a contrast agent-free and radiation-free imaging modality performed during free breathing, which allows quantification of static and dynamic regional ventilation and perfusion parameters in chronic pulmonary diseases.
It should be noted that some prior studies used alternative MRI methods, such as inhaled hyperpolarized xenon 129 (129Xe) MRI, to investigate gas exchange in adult patients diagnosed with post-COVID syndrome. The results revealed a lower pulmonary red blood cell-to-alveolar tissue barrier ratio in both post-hospitalized and non-hospitalized post-COVID participants, suggesting abnormal oxygen and carbon dioxide gas exchange. The complementarity of these imaging modalities suggests that a multimodal approach may provide further pathophysiologic insights. https://discovermednews.com/long-covid-patients-have-abnormal-gas-exchange-measured-by-129xe-mri-red-blood-cells-to-alveolar-tissue-barrier-ratio/
About the study
This study was conducted in children and adolescents with post-COVID syndrome and age and sex-matched healthy control participants with similar infection history and vaccination status. Inclusion criteria for the consecutively enrolled group with post-COVID syndrome were: age less than 18 years, confirmed SARS-CoV-2 infection, symptoms persisting for at least 12 weeks following SARS-CoV-2 infection, and normal electrocardiographic examination. Inclusion criteria for the healthy control group were normal electrocardiographic and clinical examinations and spirometry findings. Exclusion criteria were acute SARS-CoV-2 infection, pregnancy, smoking history, cardiopulmonary or other critical diseases, the use of lung medication, and contraindications to MRI.
All participants in the current study underwent lung MRI, pulmonary function testing, physical examination, and symptom assessment through anamnesis interviews on the same day. Pulmonary function was determined by measuring the predicted values for forced expiratory volume in 1 second and forced vital capacity according to the recommendations of the American Thoracic Society. Symptom severity and functional disability were assessed by the Bell score.
PREFUL MRI parameters, such as regional ventilation, flow-volume loop correlation metric, quantified perfusion, ventilation and perfusion defect percentages, and ventilation-perfusion ratios, were compared between post-COVID participants and controls.
Results
The study sample included 54 participants (27 participants with post-COVID syndrome and 27 matched control participants). The median age was 15 years (11–17 years) for all participants. In both groups, 13 of 27 participants (48%) were boys. The groups did not differ in height, weight, body surface area, and body mass index.
In 24 participants with post-COVID syndrome, SARS-CoV-2 infection was confirmed with the reverse transcriptase-polymerase chain reaction test, in two participants with professional antigen tests, and in one with a self-administered antigen test. 84% of participants with post-COVID syndrome (23 of 27) and 89% (24 of 27) of control participants were vaccinated.
In participants with post-COVID syndrome, the median time between a confirmed COVID-19 diagnosis and presentation at the post-COVID pediatric outpatient clinic was 30 weeks. None of the participants required hospitalization.
18 different clinical symptoms were identified in the post-COVID pediatric patients, with an average of 5.3 symptoms per participant (5.9 for males and 4.7 for females). All participants reported fatigue, followed by reduced physical capacity (96%), shortness of breath (64%), difficulties with concentration (56%), dyspnea (44%), insomnia (37%), muscle pain (33%), dizziness (33%), headaches (39%), chest pain (26%), abdominal pain (26%), and joint pain (22%).
In all participants with post-COVID syndrome, the triad of symptoms that included fatigue, reduced physical capacity, and shortness of breath emerged as the most prevalent (59%). Among female participants, fatigue, decreased physical capacity, and sleep disorders or concentration difficulties were the most common symptoms (reported by 53%).
A subgroup of 21 post-COVID participants (14 males and 7 females) had cardiopulmonary symptoms, such as reduced physical capacity, and at least one lung symptom, such as shortness of breath, dyspnea, or bronchial hypersensitivity.
Pulmonary function testing showed normal results in all participants.
PREFUL MRI Parameters
PREFUL MRI demonstrated that regional ventilation and perfusion were lower in children and adolescents with post-COVID syndrome than in healthy control participants. There was no evidence of differences between groups for all other ventilation parameters.
The post-COVID subgroup with cardiopulmonary symptoms exhibited lower dynamic ventilation (i.e., flow-volume loop correlation metric) and increased ventilation and perfusion defects compared with control participants.
Researchers also analyzed the potential correlation between PREFUL MRI parameters, pulmonary function testing, fatigue severity, and cardiopulmonary measures. There was no correlation between ventilation or perfusion PREFUL parameters and pulmonary function tests in children and adolescents with post-COVID syndrome. However, there were correlations between a greater lung perfusion and a greater severity of chronic fatigue and between a higher ventilation-perfusion mismatch (exclusive perfusion defect) and increased heart rate.
Images show coronal sections of phase-resolved functional lung MRI defect maps in (A) a 17-year-old male participant with post-COVID-19 condition and cardiopulmonary symptoms with a ventilation defect percentage of 17%, a perfusion defect percentage of 16%, a ventilation/perfusion (V/Q) match healthy percentage of 64%, and a V/Q mismatch defect of 3%. (B) a healthy control participant, with a ventilation defect percentage of 9%, a perfusion defect percentage of 5%, a V/Q match healthy percentage of 86%, and no V/Q mismatch defect.
Conclusion
The authors emphasized that, to their knowledge, this study represents the first comprehensive assessment of functional lung parameters using an advanced MRI technique in an extensive, well-characterized sample of children and adolescents with post-COVID syndrome. Although global lung function tests showed no significant differences between the groups, PREFUL MRI parameters revealed subtle pulmonary changes in children and adolescents with post-COVID syndrome, such as reduced regional ventilation and perfusion. According to the authors, increased dynamic ventilation defects may indicate underlying structural abnormalities, such as potential remnants of atelectasis or early fibrotic changes.
Additionally, higher perfusion defects observed in the post-COVID subgroup with cardiopulmonary symptoms may involve incomplete recovery due to microthrombotic remnants, immune cell accumulation, endotheliitis, and platelet adhesion within a thrombogenic microenvironment. Alternatively, subtle right cardiac abnormalities may contribute to these pulmonary circulation changes.
As conventional pulmonary function tests may underestimate the extent of respiratory involvement in pediatric patients with post-COVID syndrome, these findings improve the understanding of post-COVID pathophysiology and provide a basis for future research. The authors concluded that further research should prioritize multicenter longitudinal studies with larger cohorts to evaluate these findings and lung abnormalities at different stages after COVID-19 infection.
This article was published in Radiology.
Journal Reference
Pöhler GH, Voskrebenzev A, Heinze M-L et al. Phase-resolved Functional Lung MRI Reveals Distinct Lung Perfusion Phenotype in Children and Adolescents with Post–COVID-19 Condition. Radiology 2025; 314(2): e241596. (Open Access) https://doi.org/10.1148/radiol.241596
