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      Radiological Findings of COVID-19 in Children: A Systematic Review and Meta-Analysis

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          Abstract

          Background

          The majority of the children with SARS-CoV-2 infection present with respiratory symptoms, hence various chest imaging modalities have been used in the management. Knowledge about the radiological findings of coronavirus disease (COVID-19) in children is limited. Hence, we systematically synthesized the available data that will help in better management of COVID-19 in children.

          Methods

          Four different electronic databases (MEDLINE, EMBASE, Web of Science and CENTRAL) were searched for articles reporting radiological findings in children with COVID-19. Studies reporting thoracic radiological findings of COVID-19 in patients aged <19 years were included. A random-effect meta-analysis (wherever feasible) was performed to provide pooled estimates of various findings.

          Results

          A total of 1984 records were screened of which forty-six studies (923 patients) fulfilled the eligibility criteria and were included in this systematic review. A chest computed tomography (CT) scan was the most frequently used imaging modality. While one-third of the patients had normal scans, a significant proportion (19%) of clinically asymptomatic children had radiological abnormalities too. Unilateral lung involvement (55%) was frequent when compared with bilateral and ground-glass opacities were the most frequent (40%) definitive radiological findings. Other common radiological findings were non-specific patchy shadows (44%), consolidation (23%), halo sign (26%), pulmonary nodules and prominent bronchovascular marking. Interstitial infiltration being the most frequent lung ultrasound finding.

          Conclusion

          CT scan is the most frequently used imaging modality for COVID-19 in children and can detect pneumonia before the appearance of clinical symptoms. Undefined patchy shadows, grand-glass opacities and consolidation are commonly observed imaging findings in COVID-19 pneumonia.

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          Most cited references50

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          Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR

          Summary In a series of 51 patients with chest CT and RT-PCR assay performed within 3 days, the sensitivity of CT for COVID-19 infection was 98% compared to RT-PCR sensitivity of 71% (p<.001). Introduction In December 2019, an outbreak of unexplained pneumonia in Wuhan [1] was caused by a new coronavirus infection named COVID-19 (Corona Virus Disease 2019). Noncontrast chest CT may be considered for early diagnosis of viral disease, although viral nucleic acid detection using real-time polymerase chain reaction (RT-PCR) remains the standard of reference. Chung et al. reported that chest CT may be negative for viral pneumonia of COVID-19 [2] at initial presentation (3/21 patients). Recently, Xie reported 5/167 (3%) patients who had negative RT-PCR for COVID-19 at initial presentation despite chest CT findings typical of viral pneumonia [3]. The purpose of this study was to compare the sensitivity of chest CT and viral nucleic acid assay at initial patient presentation. Materials and Methods The retrospective analysis was approved by institutional review board and patient consent was waived. Patients at Taizhou Enze Medical Center (Group) Enze Hospital were evaluated from January 19, 2020 to February 4, 2020. During this period, chest CT and RT-PCR (Shanghai ZJ Bio-Tech Co, Ltd, Shanghai, China) was performed for consecutive patients who presented with a history of 1) travel or residential history in Wuhan or local endemic areas or contact with individuals with individuals with fever or respiratory symptoms from these areas within 14 days and 2) had fever or acute respiratory symptoms of unknown cause. In the case of an initial negative RT-PCR test, repeat testing was performed at intervals of 1 day or more. Of these patients, we included all patients who had both noncontrast chest CT scan (slice thickness, 5mm) and RT-PCR testing within an interval of 3 days or less and who had an eventual confirmed diagnosis of COVID-19 infection by RT-PCR testing (Figure 1). Typical and atypical chest CT findings were recorded according to CT features previously described for COVD-19 (4,5). The detection rate of COVID-19 infection based on the initial chest CT and RT-PCR was compared. Statistical analysis was performed using McNemar Chi-squared test with significance at the p <.05 level. Figure 1: Flowchart for patient inclusion. Results 51 patients (29 men and 22 women) were included with median age of 45 (interquartile range, 39- 55) years. All patients had throat swab (45 patients) or sputum samples (6 patients) followed by one or more RT-PCR assays. The average time from initial disease onset to CT was 3 +/- 3 days; the average time from initial disease onset to RT-PCR testing was 3 +/- 3 days. 36/51 patients had initial positive RT-PCR for COVID-19. 12/51 patients had COVID-19 confirmed by two RT-PCR nucleic acid tests (1 to 2 days), 2 patients by three tests (2-5 days) and 1 patient by four tests (7 days) after initial onset. 50/51 (98%) patients had evidence of abnormal CT compatible with viral pneumonia at baseline while one patient had a normal CT. Of 50 patients with abnormal CT, 36 (72%) had typical CT manifestations (e.g. peripheral, subpleural ground glass opacities, often in the lower lobes (Figure 2) and 14 (28%) had atypical CT manifestations (Figure 3) [2]. In this patient sample, difference in detection rate for initial CT (50/51 [98%, 95% CI 90-100%]) patients was greater than first RT-PCR (36/51 [71%, 95%CI 56-83%]) patients (p<.001). Figure 2a: Examples of typical chest CT findings compatible with COVID-19 pneumonia in patients with epidemiological and clinical presentation suspicious for COVID-19 infection. A, male, 74 years old with fever and cough for 5 days. Axial chest CT shows bilateral subpleural ground glass opacities (GGO). B, female, 55 years old, with fever and cough for 7 days. Axial chest CT shows extensive bilateral ground glass opacities and consolidation; C, male, 43 years old, presenting with fever and cough for 1 week. Axial chest CT shows small bilateral areas of peripheral GGO with minimal consolidation; D, female, 43 years old presenting with fever with cough for 5 days. Axial chest CT shows a right lung region of peripheral consolidation. Figure 2b: Examples of typical chest CT findings compatible with COVID-19 pneumonia in patients with epidemiological and clinical presentation suspicious for COVID-19 infection. A, male, 74 years old with fever and cough for 5 days. Axial chest CT shows bilateral subpleural ground glass opacities (GGO). B, female, 55 years old, with fever and cough for 7 days. Axial chest CT shows extensive bilateral ground glass opacities and consolidation; C, male, 43 years old, presenting with fever and cough for 1 week. Axial chest CT shows small bilateral areas of peripheral GGO with minimal consolidation; D, female, 43 years old presenting with fever with cough for 5 days. Axial chest CT shows a right lung region of peripheral consolidation. Figure 2c: Examples of typical chest CT findings compatible with COVID-19 pneumonia in patients with epidemiological and clinical presentation suspicious for COVID-19 infection. A, male, 74 years old with fever and cough for 5 days. Axial chest CT shows bilateral subpleural ground glass opacities (GGO). B, female, 55 years old, with fever and cough for 7 days. Axial chest CT shows extensive bilateral ground glass opacities and consolidation; C, male, 43 years old, presenting with fever and cough for 1 week. Axial chest CT shows small bilateral areas of peripheral GGO with minimal consolidation; D, female, 43 years old presenting with fever with cough for 5 days. Axial chest CT shows a right lung region of peripheral consolidation. Figure 2d: Examples of typical chest CT findings compatible with COVID-19 pneumonia in patients with epidemiological and clinical presentation suspicious for COVID-19 infection. A, male, 74 years old with fever and cough for 5 days. Axial chest CT shows bilateral subpleural ground glass opacities (GGO). B, female, 55 years old, with fever and cough for 7 days. Axial chest CT shows extensive bilateral ground glass opacities and consolidation; C, male, 43 years old, presenting with fever and cough for 1 week. Axial chest CT shows small bilateral areas of peripheral GGO with minimal consolidation; D, female, 43 years old presenting with fever with cough for 5 days. Axial chest CT shows a right lung region of peripheral consolidation. Figure 3a: Examples of chest CT findings less commonly reported in COVID-19 infection (atypical) in patients with epidemiological and clinical presentation suspicious for COVID-19 infection. A, male, 36 years old with cough for 3 days. Axial chest CT shows a small focal and central ground glass opacity (GGO) in the right upper lobe; B, female, 40 years old. Axial chest CT shows small peripheral linear opacities bilaterally. C, male, 38 years old. Axial chest CT shows a GGO in the central left lower lobe; D, male, 31 years old with fever for 1 day. Axial chest CT shows a linear opacity in the left lower lateral mid lung. Figure 3b: Examples of chest CT findings less commonly reported in COVID-19 infection (atypical) in patients with epidemiological and clinical presentation suspicious for COVID-19 infection. A, male, 36 years old with cough for 3 days. Axial chest CT shows a small focal and central ground glass opacity (GGO) in the right upper lobe; B, female, 40 years old. Axial chest CT shows small peripheral linear opacities bilaterally. C, male, 38 years old. Axial chest CT shows a GGO in the central left lower lobe; D, male, 31 years old with fever for 1 day. Axial chest CT shows a linear opacity in the left lower lateral mid lung. Figure 3c: Examples of chest CT findings less commonly reported in COVID-19 infection (atypical) in patients with epidemiological and clinical presentation suspicious for COVID-19 infection. A, male, 36 years old with cough for 3 days. Axial chest CT shows a small focal and central ground glass opacity (GGO) in the right upper lobe; B, female, 40 years old. Axial chest CT shows small peripheral linear opacities bilaterally. C, male, 38 years old. Axial chest CT shows a GGO in the central left lower lobe; D, male, 31 years old with fever for 1 day. Axial chest CT shows a linear opacity in the left lower lateral mid lung. Figure 3d: Examples of chest CT findings less commonly reported in COVID-19 infection (atypical) in patients with epidemiological and clinical presentation suspicious for COVID-19 infection. A, male, 36 years old with cough for 3 days. Axial chest CT shows a small focal and central ground glass opacity (GGO) in the right upper lobe; B, female, 40 years old. Axial chest CT shows small peripheral linear opacities bilaterally. C, male, 38 years old. Axial chest CT shows a GGO in the central left lower lobe; D, male, 31 years old with fever for 1 day. Axial chest CT shows a linear opacity in the left lower lateral mid lung. Discussion In our series, the sensitivity of chest CT was greater than that of RT-PCR (98% vs 71%, respectively, p<.001). The reasons for the low efficiency of viral nucleic acid detection may include: 1) immature development of nucleic acid detection technology; 2) variation in detection rate from different manufacturers; 3) low patient viral load; or 4) improper clinical sampling. The reasons for the relatively lower RT-PCR detection rate in our sample compared to a prior report are unknown (3). Our results support the use of chest CT for screening for COVD-19 for patients with clinical and epidemiologic features compatible with COVID-19 infection particularly when RT-PCR testing is negative.
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            SARS-CoV-2 Infection in Children

            To the Editor: As of March 10, 2020, the 2019 novel coronavirus (SARS-CoV-2) has been responsible for more than 110,000 infections and 4000 deaths worldwide, but data regarding the epidemiologic characteristics and clinical features of infected children are limited. 1-3 A recent review of 72,314 cases by the Chinese Center for Disease Control and Prevention showed that less than 1% of the cases were in children younger than 10 years of age. 2 In order to determine the spectrum of disease in children, we evaluated children infected with SARS-CoV-2 and treated at the Wuhan Children’s Hospital, the only center assigned by the central government for treating infected children under 16 years of age in Wuhan. Both symptomatic and asymptomatic children with known contact with persons having confirmed or suspected SARS-CoV-2 infection were evaluated. Nasopharyngeal or throat swabs were obtained for detection of SARS-CoV-2 RNA by established methods. 4 The clinical outcomes were monitored up to March 8, 2020. Of the 1391 children assessed and tested from January 28 through February 26, 2020, a total of 171 (12.3%) were confirmed to have SARS-CoV-2 infection. Demographic data and clinical features are summarized in Table 1. (Details of the laboratory and radiologic findings are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.) The median age of the infected children was 6.7 years. Fever was present in 41.5% of the children at any time during the illness. Other common signs and symptoms included cough and pharyngeal erythema. A total of 27 patients (15.8%) did not have any symptoms of infection or radiologic features of pneumonia. A total of 12 patients had radiologic features of pneumonia but did not have any symptoms of infection. During the course of hospitalization, 3 patients required intensive care support and invasive mechanical ventilation; all had coexisting conditions (hydronephrosis, leukemia [for which the patient was receiving maintenance chemotherapy], and intussusception). Lymphopenia (lymphocyte count, <1.2×109 per liter) was present in 6 patients (3.5%). The most common radiologic finding was bilateral ground-glass opacity (32.7%). As of March 8, 2020, there was one death. A 10-month-old child with intussusception had multiorgan failure and died 4 weeks after admission. A total of 21 patients were in stable condition in the general wards, and 149 have been discharged from the hospital. This report describes a spectrum of illness from SARS-CoV-2 infection in children. In contrast with infected adults, most infected children appear to have a milder clinical course. Asymptomatic infections were not uncommon. 2 Determination of the transmission potential of these asymptomatic patients is important for guiding the development of measures to control the ongoing pandemic.
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              Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding

              We report epidemiological and clinical investigations on ten pediatric SARS-CoV-2 infection cases confirmed by real-time reverse transcription PCR assay of SARS-CoV-2 RNA. Symptoms in these cases were nonspecific and no children required respiratory support or intensive care. Chest X-rays lacked definite signs of pneumonia, a defining feature of the infection in adult cases. Notably, eight children persistently tested positive on rectal swabs even after nasopharyngeal testing was negative, raising the possibility of fecal–oral transmission.
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                Author and article information

                Journal
                J Trop Pediatr
                J. Trop. Pediatr
                tropej
                Journal of Tropical Pediatrics
                Oxford University Press
                0142-6338
                1465-3664
                21 July 2020
                : fmaa045
                Affiliations
                [f1 ] Department of Pediatrics, Post Graduate Institute of Medical Education and Research , Chandigarh 160012, India
                [f2 ] Department of Pediatrics, All India Institute of Medical Sciences , New Delhi 110029, India
                [f3 ] Department of Radiodiagnosis and Imaging, Government Medical College and Hospital , Chandigarh 160032, India
                Author notes
                Correspondence: Jaivinder Yadav, Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India. E-mail < jai1984yadav@ 123456gmail.com >.

                Jogender Kumar and Jitendra Meena contributed equally to this work as first author.

                Author information
                http://orcid.org/0000-0002-0464-9689
                Article
                fmaa045
                10.1093/tropej/fmaa045
                7454935
                32692815
                c5bd4d28-59a9-46c1-912b-1af55c1282f0
                © The Author(s) [2020]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

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                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                History
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                Pages: 8
                Categories
                Original Paper
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                Pediatrics
                computed tomography,lung ultrasound,ground-glass opacity,pneumonia,imaging,covid-19
                Pediatrics
                computed tomography, lung ultrasound, ground-glass opacity, pneumonia, imaging, covid-19

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