Patients and clinical findings
The final study population included 140 children, after excluding 8 subjects with poor-quality images that were non-diagnostic. Participants included 69 boys and 71 girls, with a median age of 6.3 years, and an interquartile range of 1.6–12.1 years. All participants had COVID-19 infection confirmed by RT-PCR (n=126, 90%) or immunoglobulin (IgM) test (n=14, 10%). One hundred thirty-one children had radiography (108 had only radiographs), and 32 children had CT (9 had only CT). Table 1 summarizes the demographic, clinical and radiologic findings. For analytical purposes, the participants were divided into three groups: the preschool age group included children 0–6 years old (47.1%), the primary school age group included children 6–13 years old (30.0%), and the teenage group included adolescents 13–18 years old (22.9%).
Cases were submitted from Peru (n=47, 33.6%), Mexico (n=26, 18.6%), Brazil (n=16, 11.4%), Argentina (n=15, 10.7%), Colombia (n=12, 8.6%), Ecuador (n=11, 7.9%), Honduras (n=8, 5.7%), Chile (n=3, 2.1%) and El Salvador (n=2, 1.4%).
The majority of children were experiencing symptoms at the time of imaging (n=115, 82.1%), with fever the most common (n=81; 57.9%), followed by dyspnea (n=39, 27.9%) and cough (n=27, 19.3%). Indications for imaging included the assessment of SARS-CoV-2 infection in 58 children (41.4%), diagnosis of lower respiratory tract infection in 37 children (26.4%), evaluation of previous established comorbidities or acute disease in 31 children (22.1%) and detection of possible complications in 10 children (7.1%). In four children the imaging indication was not specified.
Approximately two-thirds of the children (n=92; 65.7%) had underlying conditions at the time of diagnosis of SARS-CoV-2 infection. Sixteen children had congenital heart disease (11.4%), 13 had cancer (9.3%) and 10 had an immunodeficiency disorder (7.1%). Other underlying conditions of various etiologies were documented in the remaining 53 children (Table 2).
Of all the children in this series, 62.1% (n=87) had a good clinical course and were discharged after improvement, and 29.3% (n=41) were admitted to the ICU or underwent mechanical ventilation. Twelve participants (8.6%) died despite resuscitation measures. We were unable to obtain clinical follow-up data for four children.
All of the 131 radiographs analyzed had positive findings. Radiographs were acquired on average 2.1±2.2 days after the onset of symptoms. The most frequent finding was peribronchial thickening in 93.1% (n=122) (Fig. 3), followed by ground-glass opacity in 78.6% (n=103) and vascular engorgement in 62.6% (n=82).
Ground-glass opacities were described as predominantly bilateral (n=65; 63.1%), peripheral (n=45; 43.7%) and in the lower lobes (n=48; 51.1%) (Figs. 4 and 5). Vascular engorgement was bilateral in most cases (n=59; 72.0%) and was generalized in both upper and lower lobes in 44 (53.6%) cases (Figs. 1, 5, 6, 7 and 8). Consolidation was found in 32.8% of radiographs (n=43), usually peripheral (n=11; 36.0%), unilateral (n=21; 48.8%) and affecting the lower lobes (n=27; 62.8%) (Fig. 9). Other findings are noted in Table 1.
The frequency of ground-glass opacity was significantly higher in the preschool age group (n=56; 88.9%) and lower in the teenage group (n=20; 66.7%, P=0.017). Vascular engorgement was observed significantly more frequently in primary school age children than in the preschool age and teenage groups (79% vs. 54% and 60%, P=0.036). Consolidation was significantly more frequent in teenagers and less frequent in preschoolers (53.3% vs. 23.8%, P<0.019) (Table 3).
Compared with asymptomatic children, consolidation was found more frequently in symptomatic children (37.4% vs. 12.5%, P=0.019). Findings like peribronchial thickening (100%), ground-glass opacity (83.3%) and vascular engorgement (79.2%) were more frequent in asymptomatic children; however, no statistical significance was found (Table 3).
In participants with a good clinical course who were not admitted to the ICU, peribronchial thickening was the most frequent imaging finding (97.6%), followed by ground-glass opacity (71.1%), vascular engorgement (69.9%) and consolidation (24.1%) (Table 3). Radiographs of children with a more severe clinical course (ICU admission, mechanical ventilation or death), showed ground-glass opacity in 91.7% and peribronchial thickening in 85.4%, followed by vascular engorgement in 50.0% and consolidation in 47.9% (Table 3). Therefore, radiographic findings correlated to clinical course: peribronchial thickening and vascular engorgement were the more frequent findings in children with favorable outcomes than in those who required ICU admission or died (P=0.008 and P=0.023, respectively). Consolidation and ground-glass opacity were more frequently found in children who required ICU admission or died than in those who had a milder clinical course (P=0.005 and P=0.006, respectively). See Online Supplementary Material 3.
Consolidation was found in 28.3% of radiographs taken fewer than 7 days from clinical onset compared to 61.1% in radiographs taken more than 7 days from clinical onset (P=0.006). No statistically significant association was found between the time from the onset of symptoms and other radiologic signs (Table 3 and Online Supplementary Material 3).
After excluding underlying cardiovascular disease and other conditions related to pulmonary vascular overflow (n=17), vascular engorgement was the predominant pattern in 25 children (21.9%) (Figs. 1 and 7). The pattern was most frequent in boys (60%), in the primary school group (44%) and in symptomatic children (83.3%). It was present in 16.7% of asymptomatic children. Children who were imaged <7 days after symptom onset showed vascular engorgement on the chest radiograph in 63.7% of cases. For four children with vascular engorgement on initial radiograph, the progression to ground-glass opacity or consolidation was confirmed in follow-up radiograph or CT (Figs. 8 and 9).
Chest computed tomography
Chest CT was performed in 32 children in our cohort, on average 8.8±10.1 days after the onset of symptoms. The most frequent CT findings were ground-glass opacity (n=29; 90.6%) and vascular engorgement (n=27; 84.4%) (Table 1). Ground-glass opacity was characteristically bilateral (79%), diffuse (76%) and with segmental (48%) and subpleural distributions (45%) (Fig. 10). Ill-defined ground-glass nodules were observed infrequently (Fig. 11). Regarding CT findings by age group, ground-glass opacity was present in 100% of preschoolers, 90.9% of the elementary school age group and in 83.3% of the teenagers (Table 3). Vascular engorgement was found characteristically in the lower lobes (100%) and bilaterally (84%).
Central peribronchial thickening was found in 71.9% (n=23) of the CTs. Consolidation was identified in 68.8% (n=22) of CT images, affecting two pulmonary lobes on average. Halo signs, reverse halo signs (Fig. 12) and crazy-paving pattern were present in 37.5%, 34.4% and 31.3% of CTs, respectively (Table 1). Consolidation, halo signs, reverse halo signs and crazy-paving signs were more frequent in teenagers, representing 75.0%, 50.0%, 50.0% and 41.7%, respectively (Table 3). In our case series, 28/32 (87.5%) children had an unenhanced CT, and in the 4 cases with intravenous contrast-enhanced CT, no pulmonary embolism or thrombosis was observed.
All agreement measures (kappa statistic) for the four radiologic signs and eight CT signs ranged between 0.13 and 0.58 (P<0.05) indicating slight to moderate agreement  among all reviewers. The sign with the poorest observed agreement was radiographic vascular engorgement (58.9%), whereas radiographic peribronchial thickening showed the greatest agreement (88.8%) (Table 4).