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.