key: cord-0923378-t1utq65k
authors: Chen, Amei; Huang, Junxiang; Liao, Yuting; Liu, Zaosong; Chen, Dandan; Yang, Chongzhe; Yang, Ruimeng; Wei, Xinhua
title: Differences in Clinical and Imaging Presentation of Pediatric Patients with COVID-19 in Comparison with Adults
date: 2020-04-06
journal: Radiol Cardiothorac Imaging
DOI: 10.1148/ryct.2020200117
sha: 04a0369b37ce4439c545a8ef3d4b8c772c087ea7
doc_id: 923378
cord_uid: t1utq65k

BACKGROUND: Although Coronavirus Disease 2019 (COVID-19) affects patients from all age groups, clinical and radiological features of COVID- 19 have been mainly described in adults. OBJECTIVE: To characterize and compare the initial clinical and imaging features of COVID-19 in pediatric and adult patients undergoing chest computed tomography (CT). MATERIALS AND METHODS: A total of 61 patients, consisting of 47 adults (18 years old or older) and 14 pediatric patients (younger than 18 years old) with laboratory-confirmed COVID-19 by real-time reverse transcriptase polymerase chain reaction (RT-PCR) between January 25, 2020 and February 15, 2020 were enrolled in this study. All patients underwent chest CT within 3 days after the initial RT-PCR. The clinical presentation, serum markers, and CT findings were assessed and compared between the adult and pediatric patients. RESULTS: Fever was less common in pediatric patients than in adults (6/14, 42.9% vs 39/47, 83%; p = 0.008). Leukopenia or normal, lymphopenia or normal, and increased or normal C-reactive protein were common in both groups with no difference (p > 0.05). Compared with the adults, pediatric patients had a lower rate of positive CT findings and a milder clinical grade (p = 0.004, p = 0.001 respectively). On chest CT, the number of pulmonary lobes involved was reduced in pediatric patients when compared to adults (p = 0.012). Subpleural distribution of lung opacities was a dominant feature in both groups, whereas bronchial distribution was more common in the pediatric group (p = 0.048). Among the CT features in adults, ground-glass opacities (GGO) were the most common finding (24/43, 53.5%), followed by GGO with consolidation (14/43, 27.9%). In pediatric patients, GGOs accounted for 42.9% (3/7), bronchial wall thickening occurred in 28.6% (2/7), and GGOs with consolidations and nodular opacities in 14.3% (1/7). However, these CT features did not differ in two groups, except for bronchial wall thickening, which was more commonly found in pediatric patients (p=0.048). Additionally, the semi-quantitative scores of lung involvement were higher in adults than in pediatric patients (8.89 ± 4.54 vs 1.86 ± 2.41, p < 0.001). CONCLUSIONS: Compared to adults, pediatric patients with COVID-19 showed distinctive clinical and CT. Pediatric patients tend to have milder clinical symptoms, fewer positive CTs, and less extensive involvement on imaging. Bronchial wall thickening was relatively more frequent on CT images from pediatric patients with COVID-19 in comparison with adults.

In December 2019, several cases of an unexplained respiratory disease emerged in Wuhan, China, with clinical presentation resembling viral pneumonia. Deep sequencing analysis of respiratory samples revealed a novel coronavirus (SARS-CoV-2), and the disease it causes was subsequently named Coronavirus Disease 2019, COVID-19 [1] . Cases of COVID-19 cases rapidly increased China and globally [2] [3] [4] . On March 11, 2020 , the World Health Organization (WHO) declared COVID-19 a pandemic [29] .

Similar to other pneumonias caused by coronaviruses, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) [5] [6] [7] , COVID-19 patients also present with fever, cough, dyspnea and pulmonary parenchymal opacities on chest radiographs [8] [9] [10] . Reports of SARS in 2003 showed that all age groups were susceptible, but children appeared to be less affected by the disease, with fewer and less severe cases [11] . The exact number of children worldwide affected by SARS is not known because of incomplete age classification in reported cases. It was estimated that only about 5% of people affected were under the age of 18, with no child deaths reported (WHO SARS surveillance team) [12, 13] .

Recently, epidemiological, clinical, and radiological imaging studies of COVID-19 have emerged, but almost all of them have focused on adult cases, with only a few reporting findings in children [8] [9] [10] 14] . In this study, we conducted a retrospective analysis of the clinical and radiological features of COVID-19, further comparing the differences between pediatric and adult patients.

Our Institutional Review Board approved the study and waived the requirement for informed written consent. In this study, we reviewed a convenience sample of 62 consecutive patients with COVID-19 diagnosed between January 25, 2020 and February 15, 2020 at four tertiary medical units from Guangzhou, China. Inclusion criteria for this study were as follows: (a) patients with COVID-19 confirmed by real-time polymerase chain reaction (RT-PCR) on nasopharyngeal swabs; (b) patients with a chest computed tomography (CT) scan obtained within 3 days from the initial swab test. Suboptimal CT image quality, as judged by the CT readers, was the single exclusion criterion. One patient was excluded due to excessive motion artifacts on CT. Thus, a total of 61 patients were included and were divided into two groups: patients under 18 years of age were included in the pediatric group, while patients with 18 years of age or older were included in the adult group. According to COVID-19 guidelines (Trial Version 6) released by the National Health Commission of the People's Republic of China [15] , the patients were subdivided into four clinical severity groups: mild, common, severe and fatal types.

The median time from symptom onset to CT scan was 5 days, ranging from 1 to 14 days. Chest CT examinations were obtained using multi-slice helical CT scanners (Philips Brilliance 64-slice CT, Philips, Amsterdam, Netherlands; Aquilion ONE, Toshiba Medical Systems, Otawara, Japan; GE Healthcare, Milwaukee, WI, USA; SIEMENS SOMATOM Definition CT scanner, Siemens Healthineers; Erlangen, Germany) without intravenous contrast material. The scanning range was set from the level of thoracic inlet to the lowest costophrenic angle. The imaging parameters were as follows. Adults: tube voltage, 120KV; effective mAs, 180-400mAs; collimation, 0.625 mm or 0.5mm; pitch, 0.8 or 1; reconstruction algorithm, filtered back projection; reconstruction slice thickness, 1 mm; interslice gap, -0.2 mm. The estimated effective radiation dose in adults ranged from 2.8 mSv to 3.5 mSv. Children: tube voltage, 100-120 KV; mA, automatic exposure control; collimation, 2.0 mm; pitch, 1; reconstruction algorithm: iterative-based reconstruction; reconstruction slice thickness, 0.5 mm;

interslice gap: 0 mm. The estimated effective radiation dose in pediatric patients ranged from 0.8 mSv to 1.2 mSv. During the clinical examination, 10% chloral hydrate (5-10mg /kg) was given to children under 3 years of age or those unable to cooperate (orally administered 30 minutes before the scan) to ensure the calm breathing during the scan.

The CT scans were independently reviewed by two radiologists (DDC and AMC, with 5 and 18 years of thoracic radiology experience, respectively), who were blinded to the clinical information. Any discrepancies in the interpretation were resolved by consensus reading. The distribution of lung opacities was recorded as peripheral (predominantly involving the outer 1/3 of the lungs), central (predominantly involving the inner 2/3 of the lungs), central and peripheral (no clear predominance), or peribronchial (predominantly along the bronchovascular bundles). CT images were assessed for the presence of pure ground-glass opacity (GGO), GGO with consolidation, pure consolidation, nodules, bronchial wall thickening, reticular or linear opacities, lymphadenopathy, and pleural effusions [16] . A semi-quantitative lung severity score was used to assess the extension of pulmonary involvement. Each of the 5 lung lobes was visually scored from 0 to 5 as: 0 -no involvement, 1 -1%-25% involvement, 2 -26%-50% involvement, 3 -51%-75% involvement, 4 -76%-100% involvement. The total CT score was the sum of the individual lobar scores and ranged from 0 (no involvement) to 20 (maximum involvement) [10] .

The statistical analyses were performed in R (version 3.5.1, http://www.Rproject.org) and Python (version 3.5.6, http://www.python.org). Continuous variables were presented as mean ± standard deviation and categorical data were presented as the percentage of the total, unless otherwise specified. The chi-square test or Fisher's exact test were used for testing differences in categorical data between groups.

The Kruskal-Wallis H-test was used for testing differences in ordinal variables. A two-tailed p-value < 0.05 indicated statistical significance.

The clinical and laboratory data of the 61 patients are summarized in Supplemental 

Mild, common, and severe cases accounted for 8.5% (4/47), 83.0%

(39/47) and 8.5% (4/47) of the cases in adult group, respectively, as well as accounted for 50% (7/14), 50% (7/14)and 0% (0/14) of the cases in the pediatric group, respectively. No fatalities were seen in both groups. There was a significant difference between the two groups in the clinical classification (p < 0.001), with no severe cases seen in the pediatric group.

CTs were abnormal in 91.5% (43/47) of adult patients, compared with 50% (7/14) in pediatric patients, resulting in a statistically significantly difference (p = 0.004).

The imaging characteristics of 50 patients with positive CT findings, and the comparisons of CT features between pediatric and adult patients are displayed in 

Fever, fatigue, cough, runny nose, and diarrhea were the most common clinical manifestations in our cohort of adults and pediatric patients with COVID-19. These symptoms are in concordance with previous reports in SARS and MERS, also caused by coronaviruses [6, 17, 18] .

However, we noted that fever was relative less common in pediatric patients (42.9% vs 83%). Of note, about half of the pediatric patients had no systemic symptoms, except for mild upper respiratory symptoms such as cough and runny nose; some pediatric patients were asymptomatic.

Similar findings were reported in a previous study in SARS [19] . This clinical picture is indistinguishable from other viral infections of the upper respiratory tract, thus posing a diagnostic challenge for the pediatric patients with COVID-19. In addition, two adult patients only presented with diarrhea, while it was not seen in pediatric cases.

Most of the patients in both groups presented normal leukocyte/lymphocyte counts and elevated C-reactive protein, unlike in a previous study that reported that 73% prevalence of leukopenia in adults with COVID-19 [20] . We speculate that this discrepancy could be due to differences in patient population and interval between disease onset and hospital presentation. Although the laboratory findings are not specific for viral pneumonia, the lack of leukocytosis may be helpful to distinguish COVID-19 from common bacterial infections. According to the clinical severity classification proposed by the COVID-19 guidelines (Trial Version 6) in China [15] , pediatric patients were more likely to have milder clinical presentation than adults, with a higher proportion of normal CTs (50% versus 8.5%, respectively), and less extensive disease on imaging.

Therefore, healthcare systems should consider judicious utilization of routine chest CT for assessing COVID-19 in the pediatric population, balancing the potential risks posed by ionizing radiation against the most common scenario of milder clinical and radiologic disease. Currently, the Society of Thoracic Radiology and the American College of Radiology do not support the use of chest CT for routine screening of COVID-19 [30 31] .

In accordance with several recent reports on COVID-19 CT findings [10, 21, 22] , in the adult and pediatric groups, pulmonary opacities involved both lungs and multiple lobes, in a predominant peripheral distribution.

Although peribronchial distribution was uncommonly seen in both populations, it was relatively more frequent in the pediatric group. In addition, bronchial wall thickening was also more prevalent in the pediatric group. The explanation for these observations is still unclear, and could be related to differences in distribution of the coronavirus infection along the respiratory epithelium between the two groups or to occurrence of coinfection. Further studies focusing on histologic findings of COVID-19 may shed light on these differences.

infections, such as SARS, MERS [12, 23, 24] . Notably, the pediatric population generally displayed a milder and slightly diverse range of CT manifestations when compared to adults. None of these manifestations are specific for COVID-19; therefore, differentiation from other viral and opportunistic pneumonias are needed based on clinical and laboratorial workup [25] [26] [27] [28] . Exposure history and access to RT-PCR testing is essential for making the diagnosis of COVID-19.

There were several limitations in our study. First, the sample size is small in the pediatric group, which can limit the study power. Second, we could not control for geographic factors, as our subjects were from different medical centers, or for CT scanning parameters. However, we assume that these observations may reflect the most typical scenario (Note：Normal reference range of white blood cell: 4x10 9 /L～10x10 9 /L. Normal reference range of lymphocyte count: 0.8x10 9 /L～4.0x10 9 /L (adult), 1.55x10 9 /L～ 4.8x10 9 /L(child)) 1a.

1b.

1c.

1d.

1e.

1f. 

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Chi-square test or Fisher's exact test were used for testing differences among nominal variables. The Kruskal-Wallis H-test was used for the ordinal variable. A two-tailed p-value < 0.05 indicated statistical significance