Most Children Infected With SARS-CoV-2 Have Persistent Pulmonary Dysfunction Even After Recovery

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A new German study has shockingly discovered that most children infected with the SARS-CoV-2 coronavirus have persistent and long-term pulmonary dysfunction even after so called ‘recovery’.

 The study was conducted by researchers from the Institute of Radiology and the Department of Pediatrics & Adolescent Medicine at the University Hospital Erlangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Germany along with medical scientists from the Institute for Diagnostic and Interventional Radiology, Hannover Medical School-Hannover, Germany.

The study team conducted a cross-sectional, prospective clinical trial between August and December 2021, utilizing low-field MRI on children and adolescents from a single academic medical center.
https://clinicaltrials.gov/ct2/show/NCT04990531

The clinical study involving low-field MRI showed persistent pulmonary dysfunction in both children and adolescents recovered from COVID-19 and with long COVID.
 
The study findings were published in the peer reviewed journal: Radiology (A Journal of the Radiological Society of North America-RSNA)
https://pubs.rsna.org/doi/10.1148/radiol.221250
 

The purpose of the study was to characterize both morphologic and functional changes of lung parenchyma on low-field MRI in children and adolescents with post COVID-19 compared with healthy controls. A total of 54 post COVID children and adolescents (29 recovered, 25 with long COVID) and 9 healthy controls were included.

Only one participant showed any morphologic abnormality (linear atelectasis). Using functional parameters, we found a reduction of V/Q match from 81.2±6.1% in healthy controls to 62.0±18.7% (P=.006) in the recovered group and 59.9±19.8% (P=.003) in the long COVID group. Furthermore, V/Q match was lower in COVID patients with infection less than 180 days (63.5±20.1%, P=.03), 180 to 360 days (63.15±17.5%, P=0.03) and 360 days ago (41.5±11.9%, P<.001) as compared to never-infected healthy controls (81.2±6.1%).

Similar imaging approaches to the one used in our study have already proven to be able to visualize pathologic changes in pulmonary hypertension, cystic fibrosis, and chronic obstructive pulmonary disease.27-29 Specifically for COVID-19, our findings correspond to observations in adults, where vascular17 or structural abnormalities33 persist in previously hospitalized adults.

Another technique using inhaled gas contrasts agents (Hyperpolarized 129Xe MRI) to assess lung function has already been successfully applied in adults with post COVID-19. These studies had normal findings on CT, however they did show a limitation pulmonary capillary gas diffusion.34,35 In a recent study on 34 post COVID adult patients, of whom 22 had never been hospitalized, and six controls, a correlation of 129Xe MRI parameters and CT pulmonary vascular abnormalities was described.36

Interestingly, Trinkman et al. were also able to demonstrate that one half of mostly younger adult study subjects have persistent symptoms and reduced lung function for more than two months after infection.37 These results may partly correspond to the high frequency of abnormal imaging findings in our population, wherein 28% of post COVID-19 participants still reported dyspnea and 30% shortness of breath.

The low-field MRI (0.55T) used in this study has advantages for the morphological imaging of lung parenchyma when compared to 1.5T and 3T systems.20 In contrast to studies that are mostly based on surveys or self-reported outcomes, which suggest less severe COVID-19 infections and sequelae in younger patients, our study demonstrates widespread functional lung alterations are indeed present in children and adolescents.

This expands the understanding of pediatric post-acute COVID-19 disease, particularly given the increased incidence of SARSCoV-2 infection.1 A better estimate on the prevalence on pediatric post COVID lung disease is further complicated by the inconsistent, largely symptom-based definitions of long COVID disease9 – and its limited applicability to children.

The pathophysiology of acute and post-acute pathology of COVID-19 partly originates from direct endothelial damage, local inflammation, and prothrombotic milieu.15,38,39 A proposed mechanism is the ACE2-mediated entry of SARS-CoV-2, which allows the virus to directly invade endothelial cells.15,40

This may explain manifestations such as pulmonary microangiopathy and widespread capillary microthrombi seen in autopsies from patients who died from COVID-1915 and fibrotic-like consolidations found in CT.33 Previously described14 persistent signs of inflammatory processes could not be confirmed in our study.

As children develop a robust, cross-reactive, and sustained immune response after SARS-CoV-2 infection41, the observed pulmonary dysfunction in our study is an unexpected finding.

Our study had several limitations. First, we did not compare our measurements to another reference standard, such as ventilation-perfusion scintigraphy, spirometry, or body plethysmography. However, most of these modalities either use ionization radiation, are invasive, or require active cooperation.

Second, the functional low-field MRI in our study used free-breathing all intervals, which was feasible in 93% of the pediatric post-acute COVID-19 group starting from 5 years of age. Third, our study lacked longitudinal data. Fourth, we had a low number of healthy controls. Finally, a selection bias does exist, as families with children with acute or post-acute symptomatic COVID-19 and higher disease burden might have been more likely to participate in our study.

In summary, we report persistent pulmonary dysfunction as visualized on low-field MRI in both children and adolescents recovered from COVID-19 and with long COVID. The further course and outcome of the observed changes currently remains unclear.

Our results warrant further surveillance of persistent pulmonary damage in pediatrics and adolescents after SARSCoV-2 infection.

Given the already existing diagnostic value of lung MRI42 and the translatability of the technology, these imaging approaches can be rapidly adopted to clinical routine care.

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