key: cord-0875224-ovcz0g8j
authors: Bayramoglu, Zuhal; Canıpek, Eda; Comert, Rana G; Gasimli, Nilufar; Kaba, Ozge; Yanartaş, Mehpare Sarı; Torun, Selda Hançerli; Somer, Ayper; Erturk, Sukru Mehmet
title: Imaging Features of Pediatric COVID-19 on Chest Radiography and Chest CT: A retrospective, single-center study
date: 2020-10-05
journal: Acad Radiol
DOI: 10.1016/j.acra.2020.10.002
sha: afba5d145ff3b31f4806d7703287a8d4f2a4c94a
doc_id: 875224
cord_uid: ovcz0g8j

RATIONALE AND OBJECTIVES: This study aims to reveal the imaging features of COVID-19 in children. MATERIALS AND METHODS: 69 chest radiographs and 37 chest CT examinations of 74 children (36 male; median (interquartile range) age:11 (6.25-15) years, 38 female; median (interquartile range) age: 12 (5.75-16) years) with positive real-time reverse transcription-polymerase chain reaction results between March 10 and May 31, 2020, were evaluated in this retrospective study. Differences in 0-<6, 6-<12, and 12-18 years of age groups were assessed with the Fisher's exact test or Kruskal-Wallis tests. RESULTS: Right-sided (3/69, 4.3%) or bilateral (3/69, 4.3%) ground-glass opacities without significant difference in age groups were depicted as radiographic findings related to COVID-19 in children. Opacities were either single (7/37,18.9%) or bilateral (7/37,18.9%) around the distal third of the bronchovascular bundle on CT. There was no significant difference in the median size of the largest opacities, total numbers of opacities and involved lobes, and the distance of the closest opacity to the pleura among age groups (p>0.05). The rate of ground-glass opacities with or without consolidation (17/37, 45.94%) was higher than consolidation alone (6/37,16.2%). Feeding vessel sign (16/37, 43.2%), halo sign (9/37, 24.3%), pleural thickening (6/37, 16.2%), interlobular interstitial thickening (5/37,13.5%), and lymphadenopathy (3/37, 8.1%) were other imaging findings. CONCLUSION: Unilateral or bilateral distributed ground-glass opacities often associated with feeding vessel sign, halo sign, and pleural thickening on chest CT without significant differences between age groups were findings of COVID-19 in children.

The SARS-CoV-2 is an enveloped and single-stranded RNA virus that is a member of the beta coronavirus family that has a zoonotic origin and causes ''Coronavirus Disease 2019'' which may result in severe acute respiratory distress syndrome. SARS-CoV-2 is transmitted through respiratory droplets of an infected person during coughing and sneezing, aerosols especially in crowded, and poorly ventilated rooms, and less commonly contact with or touching contaminated surfaces. The virus has affected more than 29.4 million people, with more than 933,000 deaths worldwide as of September 15, 2020. The pediatric age group (<18 years) constituted 2,572 (1.7%) of 149,082 diagnosed patients in early April in the United States with the infants (<1 year) accounting for 15% of pediatric COVID-19 cases (1) . Asymptomatic infections are more frequent in children (2) probably due to lower frequencies of exposure to SARS-CoV-2 and less matured angiotensinconverting enzyme-2 receptors (3, 4) . Radiological examinations were less commonly required in children due to the lower overall incidences of infected, symptomatic, and severe cases in the pediatric age group compared to adults. The effects of the developing immune system on disease progression and imaging findings are still puzzling for pediatric COVID- 19 . SARS-CoV-2 may result in multisystem inflammatory syndrome in children associated with fever, severe illness, the involvement of two or more organ systems in presence of increased inflammatory markers which may be caused by the post-infectious immune dysregulation. Transmission from children to older family members would be a critical problem for older family members owing to the reported higher frequency of severe illness.

Additionally, the number of the affected children who are asymptomatic especially in the initial phases of the COVID-19 increases in the setting of family clusters (4, 5) .

Diagnostic tests for COVID-19 include the real-time reverse transcription-polymerase chain reaction (RT-PCR) testing from nasopharyngeal or throat swabs, IgM and IgG antibodies against SARS-CoV-2, and the radiological examinations, including chest radiography and chest computed tomography (CT). Chest CT examinations revealed high sensitivity (97%), relatively lower specificity (65%), and were found abnormal in the majority of adult patients (75%) who were initially tested negative by real-time RT-PCR (6) .

However, the Centers for Disease Control does not recommend radiological examinations as a specific method of COVID-19 diagnosis, and confirmation of COVID-19 by viral testing is crucial even if the radiological findings are suggestive of COVID-19 (7) . Radiological manifestations of COVID-19 vary between age groups (8) . A recent study (9) reviewed the studies investigating imaging characteristics of COVID-19 in children with a small sample size (10) (11) (12) (13) (14) . In this article, we aimed to document the chest radiography and chest CT imaging findings of children with COVID-19 from a single academic center and to compare our results with the existing literature.

The present retrospective study was conducted at a single academic center (Istanbul University, Istanbul Medical Faculty, Radiology Department) and included consecutive children each were diagnosed with COVID-19 by positive real-time RT-PCR tests between March 10 to May 31, 2020. Children with negative real-time RT-PCR results were excluded.

The local ethics committee approved the study (File number: 86531). Informed consent was waived because of the retrospective nature of the study. None of the patients had a chronic cardiac, pulmonary, or hepatic disease that may lead to lymphadenopathy, pleural effusion, or pulmonary interlobular interstitial thickening which may mimic COVID-19 related findings.

Real-time RT-PCR tests were evaluated in two laboratories under the supervision of the Ministry of Health and Istanbul Medical Faculty. A total of seventy-four children with a diagnosis of COVID-19 were included (Table 1) . Chest radiographs of 69 children and chest CT examinations of 37 children) diagnosed with COVID-19 were reviewed. Patients were divided into three age groups: A) 0-<6 years (median 3, interquartile range (IQR) 2-4) years, B) 6-<12 years (median 9, IQR 8-10.25), and C) 12-18 years (median 16, IQR [14] [15] [16] [17] . Chest radiographs were not available in 5 patients, owing to the being performed in external medical centers and referred to our tertiary care center.

Thirty-three children (median age (IQR): 10 (6-15) years; male:13, female:19) had both chest CT and chest radiography examinations with a median interval of 0 days (IQR: 0-1 days) between examinations. Abnormal CT and radiographic imaging findings and the time interval between chest radiographs and chest CT examinations of pediatric patients with known real-time RT-PCR positivity were investigated retrospectively and consecutively by two radiologists (ZB, a pediatric radiologist with more than nine years of radiology experience; EC, a radiologist having more than three years of radiology experience) who were blinded to the symptoms owing to the lack of the available systematic clinical information in the database.

All examinations were obtained using a fixed X-ray device (Toshiba Rotanode E7869XX, Tochigi, Japan) reserved for the COVID-19 outbreak in the pandemic unit. Single view posteroanterior chest radiography examinations were performed in an erect posture with breath-hold in cooperative patients. Respiratory or motion artifacts preventing the evaluation were not observed on the radiographs of the patients who could not breathe hold. Therefore, all examinations were included for investigation. The exposure dose was adjusted based on the patient's age and weight, varying between 55kVp, 5 mAs, and 100 kVp, 100 mAs.

All radiographs were retrospectively searched from the database and evaluated consecutively for COVID-19 related imaging findings including peribronchial thickening (PBT), ground-glass opacities (GGOs) and consolidations (Fig. 1) , distribution of opacities (central or peripheral; unilateral or bilateral), number of the opacities, and associated abnormalities such as pleural effusion, and mediastinal or hilar lymphadenopathy according to the recommendations by the Fleischner Society (15) . The reasons for the lack of the detectability of COVID-19 on the chest radiographs were documented by comparing the abnormal chest CT findings of the patients with normal chest radiographs based on the location, distribution, size, and density of the opacities.

Children with suspicious COVID-19 related symptoms and signs regarding cough, fever, diarrhea, hypotension, dyspnea, loss of taste and smell, and myalgia underwent chest CT examinations using a 64 detector CT scanner (Aquillon 64, Toshiba Medical Systems, Tochigi, Japan) without intravenous contrast. (Weight based tube voltage: 100-120 KV, reconstruction interval: 5, pitch: 0.65; slice thickness: 5 mm). Intravenous contrast agents are used to evaluate for complicated pneumonia with necrosis, vascular complications, and mediastinal enlargement in children in our department. None of the children with a suspect of COVID-19 were initially undergoing contrast-enhanced chest CT. Cooperative patients were asked to hold their breath. All chest CT images were reviewed according to the recommendations by the Fleischner Society (15) . Findings compatible with chronic sequelae such as air trapping due to bronchial atresia, calcific nodules, or calcific lymph nodes were described as irrelevant imaging findings for COVID-19. Findings other than those in children with COVID-19 were classified according to age groups.

COVID-19 related imaging findings included pulmonary opacities (either as GGO or consolidation), pulmonary nodules (except for calcific or non-infectious interstitial nodules), pleural and interlobular septal thickening, lymph nodes (short-axis diameter greater than 10 mm), and pleural effusion on chest CT were noted in each patient. Distribution of the opacities in the lung lobes and around the proximal, middle, or distal third of the bronchovascular bundles was noted. The total number of the involved lobes and opacities were calculated. Distribution was categorized as single, multiple (in a lung or a lobe), and bilateral. The largest dimension of the largest opacity and the distance of the closest opacity to the pleura were measured. The involvement pattern (nodular or peribronchial), margins (well-defined or ill-defined), density category of the opacities, presence of associated imaging findings (feeding vessel sign, halo sign, air bronchogram, tree-in-bud sign, atoll sign, and assessed using Fisher's exact test to compare 0-<6 years vs 6-<12 years, 6-<12 years vs 12-18 years, and 0-<6 years vs 12-18 years of age groups. Non-parametric quantitative data were expressed as median (IQR) and compared with the Kruskal-Wallis test among age groups. Spearman's correlation analysis was performed to assess the association of quantitative data. A p-value of less than 0.05 is considered statistically significant.

The descriptive statistics related to gender, age groups, and test results of the patients are given in Table 1 . No statistically significant differences were found regarding the ages of the patients based on gender (p=0.79), chest radiography (p=0.1), and chest CT findings (p=0.77).

Chest radiography examination results are given in Table 2 . Abnormal findings on chest radiography were depicted in 18.8% (13/69) of the patients, 6 in 0-<6 years, 1 in 6-<12 years, and 6 in the 12-18 years of age groups. No significant differences were found regarding unilateral or bilateral involvement, numbers of opacities, and central or peripheral distribution by age groups (p=1). PBT was seen in 7 patients in the 0-<12 years of age group and GGOs were seen in 2 patients in the 0-6 year age group and in 3 patients in the 12-18

year age group (p=0.02). Pleural effusion was encountered in only one patient (1/69, 1.4 %), in the 12-18 year age group.

The interval from the symptom onset to chest CT examinations was 2±1.4 days (median (IQR): 2 (1-3) days). Most of the patients (30/37, 81%) with CT examination were in the first four days of the symptoms corresponding to early stage, and 19 % (7/37) were in the progressive stage.

Chest CT examination results based on distribution and quantitative CT parameters are given in Table 3 . Abnormalities were depicted in 2 of 3 patients in the 0-<6 years, 6 of 10 patients in 6-<12 years, and 11 of 24 patients in the 12-18 years of age groups. Location at the lower lobes (18/37, 48.65%) and around 1/3 distal to the bronchovascular bundles (17/37, 45.9%) were depicted distributions of COVID-19 related opacities in children. Opacities were sometimes single (7/37, 18.9%) or distributed bilaterally (7/37,18.9%). There were no significant differences between age groups in the median values of the total number of opacities (p=0.73) and involved lobes (p=0.55), size (p=0.86) of the largest opacity, the distance of the closest opacity to the pleura (p=0.53).

Chest CT examination results based on the shape and density of the COVID-19 related imaging findings are given in Table 4 . Opacity pattern was identified either as peribronchial type (12/37, 32.4%) or as nodular (12/ There were statistically significant positive correlations among the total number of opacities with the total number of involved lobes (p=0.001, r=0.91) and the largest opacity size (p=0.038, r=0.52). The distance of the closest opacity to the pleura decreases with increased opacity numbers without statistical significance (p=0.07, r=-0.47).

We investigated the imaging findings of pediatric COVID-19 on chest radiography and chest CT with a detailed classification. Imaging findings were compared among three different age groups. Findings on CT were lower lobe predominant, peripherally distributed, single or bilateral GGOs. The distinctive CT findings were feeding vessel sign, halo sign, and pleural thickening. Scores on the systems developed for adults were mostly corresponding to low suspicion level.

Real-time RT-PCR is the gold standard in the diagnosis of COVID-19 and is recommended in symptomatic patients (19) . However, children in the initial phases of the COVID-19 may be asymptomatic but can cause the spread of COVID-19 to family members.

Due to the lack of apparent abnormalities in routine blood and other laboratory tests in a considerable number of children, low-dose CT examination would be a diagnostic tool only in high-prevalence environments in which there is no appropriate access to viral testing.

Thus, the transmission of SARS-CoV-2 to the family members or vulnerable pediatric patients may be reduced in that manner (20) . Children with positive real-time RT-PCR results may be asymptomatic in up to one third with negative imaging findings, but a considerable number of patients (43/50;86%) were positive on CT investigation (21) . Being aware of COVID-19 related patterns on CT examination would be discriminatory in selected cases to decide whether to admit children into the SARS-CoV-2 free service or a pandemic service.

However, the opacity patterns were found to be subtle and different when compared to adults.

The depicted CT positivity ratio in the current study (19/37, 51.3%) was considerably higher than a recent study reported normal CT studies in 77% of 30 children (11) . However, the depicted CT positivity ratio (51.3%) was still insufficient to distinguish pediatric COVID-19

cases reliably. CT examinations should not be a screening tool for pediatric COVID-19 diagnosis owing to the frequently mild or moderate clinical courses of the pediatric COVID-19 cases, less commonly encountered findings with high suspicion of COVID-19, as well as the negative aspects of the radiation exposure (22) . On the other hand, there has been an identified real-time RT-PCR negative but a radiologically positive group with definite SARS-CoV-2 exposure (21) . Because real-time RT-PCR test results are affected by sampling operations and timing owing to the cycle thresholds in the sources (6) .

In this analysis, the majority of the causes for normal-appearing chest radiographs for COVID-19 while there have been positive findings on the chest CT were due to low-density opacities (7/23, 30%), small-sized opacities (6/23, 26%), or basal-located opacities obscured with the diaphragm and hepatic dome on posteroanterior chest radiography (4/23, 17%).

Chest radiography findings of COVID-19 were GGOs and/or PBT. PBT is unusual for adult COVID-19 findings (23) but typical for viral pneumonia in children. Abnormal findings in children with the severe acute respiratory syndrome have been reported to be multifocal in 1/3 of cases with unilateral and lower zone predominance in the early phase (24) .

Coronavirus-borne diseases as SARS or SARS-CoV-2 may be depicted in a small number of children by radiographs. SARS-CoV-2 causes acute respiratory distress syndrome due to diffuse alveolar hemorrhage, diffuse intravascular coagulation, intussusceptive angiogenesis (25) , and nearly total occlusion of vessels by complement associated thrombosis (26) . Opacities were generally closer than 2 mm to the pleura suggesting that their peripheral distributions are related to the involvement of small-sized pulmonary vessels. The low-density opacities as

GGOs are corresponding to a hyaline membrane, and pulmonary edema in 97% and presence of alveolar hemorrhage in 87% of the cases (27, 28) . The feeding vessels disclose angiocentric inflammation. Pulmonary blood vessels are thinner in children, and changes in size may be subtle due to respiratory artifacts and section thickness. Although vascular enlargement was not common in the pediatric cases, the ''feeding vessels'' passing through the central part of the nodules or peribronchial opacities with a higher density compared to the intact section would be apparent and easy to detect the angiocentric inflammation as an observational parameter and alternative sign for vascular enlargement. Additionally, multiple feeding arteries around peripheral -subpleural opacity may be entitled ''bridging vessels'' and may also strengthen the angiocentric inflammation at the peripheral pulmonary vascular network.

There has been a peripheral and lower lobe predominant distribution pattern with bilateral numerous opacities in our pediatric cohort, similar to previous studies (11, 21) .

There is no available data in the literature in terms of the total number of the opacities and the distance of COVID-19 related opacities to the pleura in the children. We described GGOs or consolidations in 51.3% of our cohort with the GGOs presenting a higher rate without a significant difference between age groups. A predominant GGO pattern (8, 11, 22, 26, 29) followed by a GGO pattern accompanied by consolidations (8, 14, 30, 31) and consolidations alone (32) were depicted in several studies. A higher incidence of consolidations with or without halo sign compared to GGOs with or without consolidations was also reported in a recent study (32) . The density pattern of the opacities would depend on the stage of the disease. The surrounding halo sign is commonly associated with segmental consolidations (14) . PBT is uncommon in the adult population and nonspecific for COVID-19 but is depicted in children with COVID-19 (12) . On the other hand, interlobular septal thickening associated with GGOs (5/37, 13.5%) were less frequently depicted compared to adults. Nodular shaped consolidations and perivascular distributed nodules were not noted in the adult population. We demonstrated a nodular pattern in one of three children (32.4%) compatible with the literature (11, 12, 26, 31) . The halo sign (11) detection ratio was lower than the previous study, which included a smaller sample size. Most of the patients did not score high on the new scoring systems adjusted for adults. Therefore, these scoring systems seem to be not applicable to children. Although given a higher number of participants with positive COVID-19 related imaging findings, this population is still insufficient to reveal a common lexicon for COVID-19 radiological evaluation in the pediatric population due to heterogeneous opacity patterns. Therefore, a modified scoring system adapted for children is needed based on vascular and perivascular changes. This study has some limitations. First, superimposed or concomitant pneumonia due to different infectious agents was not excluded via laboratory tests because of the restricted viral respiratory panel tests in our laboratory owing to the real-time RT-PCR test load due to the COVID-19 pandemic. Second, although this study frequently reflects the early imaging findings of pediatric COVID-19, most of patients were in the early phases of the disease, and opacity characteristics may change over time, especially in the progressive stage.

In conclusion, pediatric COVID-19 related imaging findings may be subtle both on chest radiography and also chest CT examinations. Imaging findings reveal different and heterogeneous opacity patterns compared to adults. The findings of pediatric COVID-19 can be handled in different categories than those defined for adults. In symptomatic cases, pediatric COVID-19 awareness can be created by the described findings until the real-time RT-PCR results are obtained. Given the negative aspects of radiation exposure, higher incidence of indeterminate appearances of COVID-19 related imaging findings in children, chest CT examinations are not essential in the diagnosis of pediatric COVID-19. a. Posteroanterior chest radiograph of a 13-year-old female patient presented with fever for two days. Chest radiography and chest CT images were obtained on the same day. The chest radiography was normal.

b. Chest CT image in the axial plan revealed a single, peripheral located, ground-glass opacity at the posterobasal segment of the right lower lobe. The opacity was obscured with the right liver lobe and diaphragm on chest radiography. 1c. Posteroanterior chest radiograph of a 10-year-old male patient presented with cough and fever for two days. Chest radiography and chest CT images were obtained on the same day.

The chest radiography revealed peripheral ground-glass opacity (arrow) at the basal segments of the right liver lobe. 1e. Posteroanterior chest radiograph of a 13-year-old male patient presented with cough and fever for two days. Chest radiography and chest CT images were obtained on the same day.

The chest radiography was interpreted as normal.

1f. Axial chest CT image of the 13-year-old male patient without contrast demonstrates bilateral, multifocal, peripherally and perivascular distributed millimetric nodular-shaped ground-glass opacities. The opacities were not detected on chest radiography due to the smaller size and lower density. day of fever and cough shows a single, peripheral ground-glass opacity and bridging vessels (arrows) around the ground-glass opacity at the laterobasal segment of the right lower lobe.

The continuous vessels at the peripheral vascular network around the opacity may suggest angiocentric inflammation. Table 5 . Categories of the chest CT findings based on classification systems and different age groups.

Coronavirus Disease 2019 in Children-United States

Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the

Chinese Center for Disease Control and Prevention

Among Children in China

A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster

Novel coronavirus SARS-CoV-2: familial spread resulting in COVID-19 pneumonia in a pediatric patient

Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases

ACR Recommendations for the use of Chest Radiography and Computed Tomography (CT) for Suspected COVID-19 Infection.American College of Radiology website

High-resolution computed tomography manifestations of COVID-19 infections in patients of different ages

Imaging findings of SARS-CoV-2 infection in pediatrics: A systematic review of coronavirus disease 2019 (COVID-19) in 850 patients

Clinical characteristics and radiological features of children infected with the 2019 novel coronavirus

CT Features of Coronavirus Disease (COVID-19) in 30 Pediatric Patients

Differences in clinical and imaging presentation of pediatric patients with COVID-19 in comparison with adults

High-Resolution Computed Tomography Manifestations of 5

Pediatric Patients With 2019 Novel Coronavirus

Clinical and CT features in pediatric patients with COVID-19 infection: Different points from adults

Fleischner Society: glossary of terms for thoracic imaging

Coronavirus disease 2019 (COVID-19) imaging reporting and data system (COVID-RADS) and common lexicon: a proposal based on the imaging data of 37 studies

CO-RADS -A categorical CT assessment scheme for patients with suspected COVID-19: definition and evaluation

Radiological Society of North America Expert Consensus Statement on Reporting Chest CT Findings Related to COVID-19. Endorsed by the Society of Thoracic Radiology, the J AM RADIOL, and RSNA

COVID-19 Diagnostic and Management Protocol for Pediatric Patients

Asymptomatic SARS-CoV-2 infection in children: a

A single-center, retrospective study of COVID-19 features in children: a descriptive investigation

Value of Chest CT as COVID 19 screening tool in children

Frequency and Distribution of Chest Radiographic Findings in COVID-19 Positive Patients

COVID-19) Pneumonia: What Radiologists Need to Know

Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases

Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet respiratory medicine

Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study. The Lancet Infectious Diseases

Chest computed tomography in children with COVID-19 respiratory infection

Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases

Zhongguo dang daierke za zhi = Chinese journal of contemporary pediatrics 2020

Clinical features and chest CT findings of coronavirus disease 2019 in infants and young children

Zhongguo dang daierke za zhi = Chinese journal of contemporary pediatrics 2020

Radiographic and Clinical Features of Children With Coronavirus Disease (COVID-19) Pneumonia

Age (