3. Inter-and intro-operator agreement
Bland-Alterman analysis revealed that LUSS derived by 2 readings from intra- and inter-observers, were highly consistent (Fig.4). Both the intra- and inter-observer reproducibility were excellent, with ICCs of 0.930 and 0.854, respectively. Intra-observer reproducibility of LUSS slightly better than that of inter-observer (Table 4).
Discussion
The SARS-Cov-2 particles enter the airways and lungs, and could reach the bronchioles and alveoli. Therefore, the lesions mostly located in the terminal alveoli and subpleural4. The pathologic findings5 of COVID-19 showed diffuse lesions of the alveoli with mucus exudation, which caused consolidation of the lung. Infants and children are also considered to be susceptible to COVID-19, and mainly infected from family cluster outbreak6. Compared with infected adults, infected children experienced differently, and most appear to have a milder clinical course. Asymptomatic patients are not uncommon in pediatric population, some of whom have radiologic features of pneumonia7. Therefore, it is important for us to recognize the pediatric COVID-19 patients, using imaging modalities. Our colleague has reported1 3 neonates were identified SARS-CoV-2 infection and associated pneumonia in 33 neonates born to mothers with COVID-19. Our study demonstrated the similar scene, and all the COVID-19 neonates showed mild symptoms and pneumonia on chest CT or X-ray.
CT features in pediatric patients with COVID-19 infection showed different points from adults. Most of children stay in the early stage, and less move into the advanced and critical stage. On CT images, ground glass opacities (GGO) appear near the pleura, but pleural effusion is rare. However, compared to adults, the lesions distribution is less extensive and some atypical GGO appear in children8. Cause most of pediatric COVID-19 cases stay in the early stage and located in the peripheral area under the pleura with limited extension towards the pulmonary hilum, ultrasonic modality could also show the distribution of COVID-19 lesions.
Lung ultrasound (LUS) cannot create direct imaging of the pulmonary parenchyma, but can be used for the diagnosis by utilizing artefacts formed by different pathological changes. When air-to-liquid ratio of the lungs is changed by specific lung diseases, especially when the pleura gets involved, LUS images can be changed and help located the lung lesions. All LUS signs and patterns described in the adult are alike in neonates and children, in both normal and pathological conditions9. The advantage of LUS in pediatric population is also related to the small size of the chest, which allows an optimal, visualization of the lungs in most cases, irrespective of the depth of the main target of the examination. A number of studies have described the benefits of LUS in the diagnosis of TTN, RDS, bronchiolitis in neonates. Compared with chest X-ray, LUS is valuable in detecting pediatric pneumonia with good sensitivity and specificity, especially companied with lung consolidation10. However, it can reduce 38.8% CXR usage11 in pediatric population.
Considering children’s higher radio-sensitivity and free radiation of this technique, neonates may benefit from LUS. Launching a LUS in their neonatal intensive care unit (NICU) roughly halved the number of chest radiograms and significantly decreased the mean radiation dose12. In fact, LUS exam during COVID-19 outbreak should be as focused as necessary to obtain diagnostic views12, but should also be comprehensive enough to avoid return to the isolation ward. Each exam should be tailored to the indication and planned in advance.
In current study, LUS presented most of the lung regions involved, and the lesions are bilateral and diffuse. Lesions distribution suggested that bilateral lower lobes and right middle lobe were mostly infected, which were similar with CT findings4,8. Abnormalities in B-lines and A-lines were the most common signs, covering all the infected regions. There may be a few B-lines in the lung fields of normal neonates at the age of 3-7 days. The abnormal increase of B-lines, usually accompanied with disappear of A-lines, represents fluid accumulation at the alveolar level and lobular space, decreased air-to-liquid ratio, and pulmonary function impairment in varying degrees. When confluent B-lines spread throughout the lung field, the sonogram shows a diffuse B-line pattern, called the white lung, which wasn’t observed in our study due to mildly symptomatic pediatric patients13. LUS showed a high sensitivity and specificity to detect lung edema by abnormal B-lines, however it was challenging to identify the etiology of edema, i.e. cardiogenic, nephrogenic or pneumonia14. We propose that it could be combined with other organ clinical and ultrasonic assessment to give a comprehensive judgment of the situation. Subpleural consolidation was another typical sign in neonatal COVID-19. It indicates lung tissue becomes non-aerated and echogenic, resulting in ultrasonic solid tissue change. If residual gas or liquid in the bronchi are visible, air bronchogram or fluid bronchogram can be presented. In our study, we only observed limited subpleural consolidation, which is inconsistent with local subpleural lesions displayed in CT images.
Since LUS detects the artefacts generated by the accumulation of fluid, we could rank the artefacts according to the air-liquid ratio and create scores reflecting lung aeration. LUSS, a three-stage classification system, could comprehensively and semi-quantitatively reflect the lung aeration function and disease severity. LUSS is well correlated with indices of oxygenation in both term and preterm neonates15, guide surfactant therapy. LUSS could assess global and regional lung aeration, and well correlated with CT quantitative analysis indices16 in ARDS. In present study, the global LUSS was obviously higher in COVID-19 group, in consistent with patients’ respiratory symptoms. The regional score also reflected variant lung aeration and severity of infectious lesions, especially in bilateral lower lobes and right middle lobe. LUSS calculation has a high inter-observer agreement regardless of the ultrasonographers’ experience15, which has also been validated in our study.
In present study, we presented the typical ultrasonic features of neonatal COVID-19 pneumonia using bedside ultrasound machine. LUSS, with excellent intra-observer and inter-observer reproducibility, can semi-quantitatively assess global and regional lung aeration and disease severity. In clinic settings, we should keep in mind that combining the imaging findings with clinic, epidemiological and etiological evidence to diagnose COVID-19. The limitation of the study was small sample size due to low morbidity in neonates. However, LUS is a free radiational, convenient, non-invasive, reproducible and reliable imaging modality in neonatal COVID-19 pneumonia diagnosis and monitoring.