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Vol 16, No 3
Vol 16, No 3 June 2020 ISSN 1708-8569
Review articles
Original articles
Brief report
Original articles
Management of children with COVID‑19: experiences from China
  Si‑Yun Xu, Li‑Li Yang, Qi Qi, Xian‑Jun Wang, Yi‑Cheng Xie, Zheng‑Yan Zhao, Qiang Shu
  [Abstract] [Full Text] [PDF]  
Diagnosis and treatment of 2019 novel coronavirus infection in children: a pressing issue
  Kun‑Ling Shen, Yong‑Hong Yang
  [Abstract] [Full Text] [PDF]  
New coronavirus: new challenges for pediatricians
  Zhi‑Min Chen, Jun‑Fen Fu, Qiang Shu
  [Abstract] [Full Text] [PDF]  
Review articles:
Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts* consensus statement
  Kunling Shen, Yonghong Yang, Tianyou Wang, Dongchi Zhao, Yi Jiang, Runming Jin, Yuejie Zheng, Baoping Xu, Zhengde Xie, Likai Lin, Yunxiao Shang, Xiaoxia Lu, Sainan Shu, Yan Bai, Jikui Deng, Min Lu, Leping Ye, Xuefeng Wang, Yongyan Wang, Liwei Gao; China National Clinical Research Center for Respiratory Diseases; National Center for Children*s Health, Beijing, China; Group of Respirology, Chinese Pediatric Society, Chinese Medical Association; Chinese Medical Doctor Association Committee on Respirology Pediatrics; China Medicine Education Association Committee on Pediatrics; Chinese Research Hospital Association
  Since the outbreak of 2019 novel coronavirus infection (2019-nCoV) in Wuhan City, China, by January 30, 2020, a total of 9692 confirmed cases and 15,238 suspected cases have been reported around 31 provinces or cities in China. Among the confirmed cases, 1527 were severe cases, 171 had recovered and been discharged at home, and 213 died. And among these cases, a total of 28 children aged from 1 month to 17 years have been reported in China. For standardizing prevention and management of 2019-nCoV infections in children, we called up an experts* committee to formulate this experts* consensus statement. This statement is based on the Novel Coronavirus Infection Pneumonia Diagnosis and Treatment Standards (the fourth edition) (National Health Committee) and other previous diagnosis and treatment strategies for pediatric virus infections. The present consensus statement summarizes current strategies on diagnosis, treatment, and prevention of 2019-nCoV infection in children.
  [Abstract] [Full Text] [PDF]  
Updated diagnosis, treatment and prevention of COVID‑19 in children: experts* consensus statement (condensed version of the second edition)
  Kun‑Ling Shen, Yong‑Hong Yang, Rong‑Meng Jiang, Tian‑You Wang, Dong‑Chi Zhao, Yi Jiang, Xiao‑Xia Lu, Run‑Ming Jin, Yue‑Jie Zheng, Bao‑Ping Xu, Zheng‑De Xie, Zhi‑sheng Liu, Xing‑wang Li, Li‑Kai Lin, Yun‑Xiao Shang, Sai‑Nan Shu, Yan Bai, Min Lu, Gen Lu, Ji‑Kui Deng, Wan‑Jun Luo, Li‑Juan Xiong, Miao Liu, Yu‑Xia Cui, Le‑Ping Ye, Jia‑Fu Li, Jian‑Bo Shao, Li‑Wei Gao, Yong‑Yan Wang, Xue‑Feng Wang; China National Clinical Research Center for Respiratory Diseases; National Center for Children*s Health, Beijing, China; Group of Respirology, Chinese Pediatric Society, Chinese Medical Association; Chinese Medical Doctor Association Committee on Respirology Pediatrics; China Medicine Education Association Committee on Pediatrics; Chinese Research Hospital Association Committee on Pediatrics; China Nongovernment Medical Institutions Association Committee on Pediatrics; China Association of Traditional Chinese Medicine, Committee on Children*s Health and Medicine Research; China News of Drug Information Association, Committee on Children*s Safety Medication; Global Pediatric Pulmonology Alliance
  In the early February, 2020, we called up an experts* committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatment criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.
  [Abstract] [Full Text] [PDF]  
Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus
  Zhi‑Min Chen, Jun‑Fen Fu, Qiang Shu, Ying‑Hu Chen, Chun‑Zhen Hua, Fu‑Bang Li, Ru Lin, Lan‑Fang Tang, Tian‑Lin Wang, Wei Wang, Ying‑Shuo Wang, Wei‑Ze Xu, Zi‑Hao Yang, Sheng Ye, Tian‑Ming Yuan, Chen‑Mei Zhang, Yuan‑Yuan Zhang
  Since December 2019, an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China. As of 8 pm, 31 January 2020, more than 20 pediatric cases have been reported in China. Of these cases, ten patients were identified in Zhejiang Province, with an age of onset ranging from 112 days to 17 years. Following the latest National recommendations for diagnosis and treatment of pneumonia caused by 2019-nCoV (the 4th edition) and current status of clinical practice in Zhejiang Province, recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the National Clinical Research Center for Child Health, the National Children*s Regional Medical Center, Childrens Hospital, Zhejiang University School of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.
  [Abstract] [Full Text] [PDF]  
Management strategies of neonatal jaundice during the coronavirus disease 2019 outbreak
  Xiao‑Lu Ma, Zheng Chen, Jia‑Jun Zhu, Xiao‑Xia Shen, Ming‑Yuan Wu, Li‑Ping Shi, Li‑Zhong Du, Jun‑Fen Fu, Qiang Shu
  The outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV) has become a most challenging health emergency. Owing to rigorous quarantine and control measures taken in China, routine neonatal health surveillance and follow-up have become challenging. Without follow-up surveillance, some rapid and progressive newborn diseases, such as bilirubin encephalopathy, may be ignored. The characteristics of onset age of kernicterus suggest that monitoring of bilirubin level at home provides a useful way to alert hospital visits and to prevent the development of extremely hyperbilirubinemia. Therefore, we developed an online follow-up program for convenient monitoring of bilirubin level of newborns that is based on our practical experiences. The aim is to make our management strategies of neonatal jaundice tailored to the infection prevention and control during the COVID-19 epidemic.
  [Abstract] [Full Text] [PDF]  
Original articles:
Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center*s observational study
  Dan Sun, Hui Li, Xiao‑Xia Lu, Han Xiao, Jie Ren, Fu‑Rong Zhang, Zhi‑Sheng Liu
Background: An outbreak of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was first detected in Wuhan, Hubei, China. People of all ages are susceptible to SARS-CoV-2 infection. No information on severe pediatric patients with COVID-19 has been reported. We aimed to describe the clinical features of severe pediatric patients with COVID-19.
Methods: We included eight severe or critically ill patients with COVID-19 who were treated at the Intensive Care Unit (ICU), Wuhan Children*s Hospital from January 24 to February 24. We collected information including demographic data, symptoms, imaging data, laboratory findings, treatments and clinical outcomes of the patients with severe COVID-19.
Results: The onset age of the eight patients ranged from 2 months to 15 years; six were boys. The most common symptoms were polypnea (8/8), followed by fever (6/8) and cough (6/8). Chest imaging showed multiple patch-like shadows in seven patients and ground-glass opacity in six. Laboratory findings revealed normal or increased whole blood counts (7/8), increased C-reactive protein, procalcitonin and lactate dehydrogenase (6/8), and abnormal liver function (4/8). Other findings included decreased CD16 + CD56 (4/8) and Th/Ts*(1/8), increased CD3 (2/8), CD4 (4/8) and CD8 (1/8), IL-6 (2/8), IL-10 (5/8) and IFN-污 (2/8). Treatment modalities were focused on symptomatic and respiratory support. Two critically ill patients underwent invasive mechanical ventilation. Up to February 24, 2020, three patients remained under treatment in ICU, the other five recovered and were discharged home.
Conclusions: In this series of severe pediatric patients in Wuhan, polypnea was the most common symptom, followed by fever and cough. Common imaging changes included multiple patch-like shadows and ground-glass opacity; and a cytokine storm was found in these patients, which appeared more serious in critically ill patients.
  [Abstract] [Full Text] [PDF]  
SARS‑CoV‑2 infection in infants under 1 year of age in Wuhan City, China
  Dan Sun, Xue Chen, Hui Li, Xiao‑Xia Lu, Han Xiao, Fu‑Rong Zhang, Zhi‑Sheng Liu
Background: The clinical characteristics and outcome of COVID-19 in children are different from those in adults. We aimed to describe the characteristics of infants under 1 year of age (excluding newborns) with COVID-19.
Methods: We retrospectively retrieved data of 36 infants with SARS-CoV-2 infection in Wuhan Children*s Hospital from January 26 to March 22, 2020. Clinical features, chest imaging findings, laboratory tests results, treatments and clinical outcomes were analyzed.
Results: The mean age of the infected infants was 6.43 months, with a range of 2每12 months. 61.11% of the patients were males and 38.89% females. 86.11% of the infants were infected due to family clustering. Cough (77.78%) and fever (47.22%) were the most common clinical manifestations. Chest CT scan revealed 61.11% bilateral pneumonia and 36.11% unilateral pneumonia. 47.22% of the infants developed complications. Increased leucocytes, neutrophils, lymphocytes, and thrombocytes were observed in 11.11, 8.33, 36.11 and 44.44% of infants, respectively. Decreased leucocytes, neutrophils, thrombocyte and hemoglobin were observed in 8.33, 19.44, 2.78 and 36.11% of infants, respectively. Increased C-reactive protein, procalcitonin, lactate dehydrogenase, alanine aminotransferase, creatine kinase and D-dimer were observed in 19.44, 67.74, 47.22, 19.44, 22.22 and 20.69% of infants, respectively. Only one infant had a high level of creatinine. Co-infections with other respiratory pathogens were observed in 62.86% of infants. CD3 (20.69%), CD4 (68.97%), CD19 (31.03%) and Th/Ts (44.83%) were elevated; CD8 (6.9%) and CD16+CD56 (48.28%) was reduced. IL-4 (7.69%), IL-6 (19.23%), IL-10 (50%), TNF-汐 (11.54%) and IFN-污 (19.23%) were elevated. Up to March 22, 97.22% of infants recovered, while a critical ill infant died. When the infant*s condition deteriorates rapidly, lymphocytopenia was discovered. Meanwhile, C-reactive protein, D-dimer, alanine aminotransferase, creatine kinase, creatinine, IL-6 and IL-10 increased significantly.
Conclusions: In the cohort, we discovered that lymphocytosis, elevated CD4 and IL-10, and co-infections were common in infants with COVID-19, which were different from adults with COVID-19. Most infants with COVID-19 have mild clinical symptoms and good prognosis.
  [Abstract] [Full Text] [PDF]  
Brief report:
Clinical features of pediatric patients with COVID‑19: a report of two family cluster cases
  Li‑Na Ji, Shuang Chao, Yue‑Jiao Wang, Xue‑Jun Li, Xiang‑Dong Mu, Ming‑Gui Lin, Rong‑Meng Jiang
Background: Coronovirus disease 2019 (COVID-19) has spread rapidly across the globe. People of all ages are susceptible to COVID-19. However, literature reports on pediatric patients are limited.
Methods: To improve the recognition of COVID-19 infection in children, we retrospectively reviewed two confirmed pediatric cases from two family clusters. Both clinical features and laboratory examination results of the children and their family members were described.
Results: The two confirmed children only presented with mild respiratory or gastrointestinal symptoms. Both of them had normal chest CT images. After general and symptomatic treatments, both children recovered quickly. Both families had travel histories to Hubei Province.
Conclusions: Pediatric patients with COVID-19 are mostly owing to family cluster or with a close contact history. Infected children have relatively milder clinical symptoms than infected adults. We should attach importance to early recognition, early diagnosis, and early treatment of infected children.
  [Abstract] [Full Text] [PDF]  
Pharmaceutical care recommendations for antiviral treatments in children with coronavirus disease 2019
  Yan Wang, Li‑Qin Zhu
  [Abstract] [Full Text] [PDF]  
Take precautions beforehand: calling for clinical trials of pediatric drugs for treating coronavirus disease 2019
  Shao‑Qing Ni, Qi‑Bo Fu, Xin‑Yi Shou, Qiang Shu
  [Abstract] [Full Text] [PDF]  
Response to children*s physical and mental needs during the COVID‑19 outbreak
  Xiao‑Bo Zhang, Yong‑Hao Gui, Xiu Xu, Da‑Qian Zhu, Yi‑Hui Zhai, Xiao‑Ling Ge, Hong Xu
  [Abstract] [Full Text] [PDF]  
What can we learn from neonates with COVID‑19?
  Tian‑Tian Xiao, Kai Yan, Lai‑Shuan Wang, Wen‑Hao Zhou
  [Abstract] [Full Text] [PDF]  
Original articles:
Molecular characteristics and antimicrobial susceptibility
  Chen Sun, Qing Wang, Wen‑Ting Li, De‑Nian Wen, Chang‑Hui Chen, Xin Yang, Wei Shi, Qing‑Hong Meng, Kai‑Hu Yao, Su‑Yun Qian
Background: The molecular characteristics and antimicrobial susceptibility of Staphylococcus aureus (S. aureus) in general pediatric wards and county-level hospitals were rarely reported in China.
Methods: Staphylococcus aureus was isolated from children hospitalized with respiratory tract infection (RTI) in Zhongjiang and Youyang counties in 2015. All isolates were typed by multilocus sequence, staphylococcal protein A, accessory gene regulator (agr), and staphylococcal cassette chromosome mec [SCCmec, for methicillin-resistant S. aureus (MRSA) only]. Polymerase chain reaction was used to screen 21 super-antigen (SAg) genes and panton每valentine leukocidin (pvl). Antimicrobial susceptibility testing was performed by E test.
Results: A total of 2136 children were enrolled. Overall, 125 (5.9%) children carried S. aureus, among which MRSA accounted for 42.4%. ST59-SCCmec type IV-t437-agr group I (58.5%) was the most prevalent genotype in MRSA, and ST188-t189-agr group I (22.2%) was the top genotype in methicillin-sensitive S. aureus (MSSA). The pvl carriage rate in MRSA and MSSA was 15.1% and 9.7%, respectively (P = 0.4112). About 96.8% of S. aureus isolates were positive for at least one SAg gene. The most common SAg gene profile in the dominant ST59 clone was sebsekseq (42.8%). All S. aureus isolates were resistant to penicillin and erythromycin (minimum inhibitory concentration 90 was > 32 and 256 mg/L to penicillin and erythromycin, respectively), but usually susceptible to other tested non-汕-lactam antimicrobials.
Conclusions: Staphylococcus aureus and MRSA were detected with a high frequency in children with RTI in county-level hospitals of China. ST59-SCCmec type IV-t437-agr group I was the dominant MRSA clone. The S. aureus isolates exhibited high resistance to penicillin and erythromycin.
  [Abstract] [Full Text] [PDF]  
Human bocavirus in children hospitalized for acute respiratory tract infection in Rome
  Laura Petrarca, Raffaella Nenna, Antonella Frassanito, Alessandra Pierangeli, Greta Di Mattia, Carolina Scagnolari, Fabio Midulla
Background: The role of human bocavirus (HBoV) as a respiratory pathogen has not been fulfilled yet. We aimed to describe clinical and serological characteristics of children with HBoV hospitalized for acute respiratory tract infection and to evaluate whether differences occur between HBoV alone and in co-infection.
Methods: We retrospectively reviewed data from 60 children (median age of 6.2 months, range 0.6-70.9) hospitalized for acute respiratory symptoms, with HBoV detected from a respiratory sample, using a reverse transcriptase-PCR for 14 respiratory viruses (including respiratory syncytial virus (RSV), influenza virus A and B, human coronavirus OC43, 229E, NL-63 and HUK1, adenovirus, rhinovirus, parainfluenza virus1-3, and human metapneumovirus).
Results: HBoV was detected alone in 29 (48.3%) patients, while in co-infection with other viruses in 31 patients (51.7%), with a peak between December and January. Among the 60 patients, 34 were bronchiolitis, 19 wheezing, 3 pneumonia, 2 upper respiratory tract infection, and 2 whooping cough. Seven children (11.6%) required admission to the paediatric intensive care unit (PICU) for respiratory failure. No differences was observed in age, family history for atopy and/or asthma, clinical presentations, chest X-ray, or laboratory findings in children with HBoV alone vs. multiple viral detection. RSV was the most frequently co-detected virus (61.3%). When compared with HBoV detection alone, the co-detection of RSV and HBoV was associated with male sex (P = 0.013), younger age (P = 0.01), and lower blood neutrophil count (P = 0.032).
Conclusions: HBoV can be detected alone and in co-infection respiratory samples of children with an acute respiratory tract infection. A cause每effect relationship between HBoV and respiratory infection is not clear, so further studies are needed to clarify this point.
  [Abstract] [Full Text] [PDF]  
Perinatal risk factors for pulmonary hemorrhage in extremely low‑birth‑weight infants
  Ting‑Ting Wang, Ming Zhou, Xue‑Feng Hu, Jiang‑Qin Liu
Background: Pulmonary hemorrhage (PH) is a life-threatening respiratory complication of extremely low-birth-weight infants (ELBWIs). However, the risk factors for PH are controversial. Therefore, the purpose of this study was to analyze the perinatal risk factors and short-term outcomes of PH in ELBWIs.
Methods: This was a retrospective cohort study of live born infants who had birth weights that were less than 1000 g, lived for at least 12 hours, and did not have major congenital anomalies. A logistic regression model was established to analyze the risk factors associated with PH.
Results: There were 168 ELBWIs born during this period. A total of 160 infants were included, and 30 infants were diagnosed with PH. Risk factors including gestational age, small for gestational age, intubation in the delivery room, surfactant in the delivery room, repeated use of surfactant, higher FiO2 during the first day, invasive ventilation during the first day and early onset sepsis (EOS) were associated with the occurrence of PH by univariate analysis. In the logistic regression model, EOS was found to be an independent risk factor for PH. The mortality and intraventricular hemorrhage rate of the group of ELBWIs with PH were significantly higher than those of the group of ELBWIs without PH. The rates of periventricular leukomalacia, moderate-to-severe bronchopulmonary dysplasia and severe retinopathy of prematurity, and the duration of the hospital stay were not significantly different between the PH and no-PH groups.
Conclusions: Although PH did not extend hospital stay or increase the risk of bronchopulmonary dysplasia, it increased the mortality and intraventricular hemorrhage rate in ELBWIs. EOS was the independent risk factor for PH in ELBWIs.
  [Abstract] [Full Text] [PDF]  
Etiology of newborn hearing impairment in Guangdong province: 10‑year experience with screening, diagnosis, and follow‑up
  Bi‑Xing Fang, Jin‑Tian Cen, Tao Yuan, Gen‑Di Yin, Jing Gu, Shu‑Qi Zhang, Zhi‑Cheng Li, Yin‑Fei Liang, Xiang‑Li Zeng
Background: Hearing impairment is one of the most common birth defects in children. Universal newborn hearing screenings have been performed for 19 years in Guangdong province, China. A screening/diagnosis/intervention system has gradually been put in place. Over the past 10 years, a relatively complete data management system had been established. In the present study, an etiological analysis of newborn cases that failed the initial and follow-up screenings was performed.
Methods: The nature and degree of hearing impairment in newborns were confirmed by a set of procedures performed at the time of initial hearing screening, rescreening and final hearing diagnosis. Then, multiple examinations were performed to explore the associated etiology.
Results: Over a period of 10 years, 720 children were diagnosed with newborn hearing loss. Among these children, 445 (61.81%) children had a clearly identified cause, which included genetic factor(s) (30.56%), secretory otitis media (13.30%), maternal rubella virus infection during pregnancy (5.83%), inner ear malformations (4.86%), maternal human cytomegalovirus infection during pregnancy (2.92%), malformation of the middle ear ossicular chain (2.50%) and auditory neuropathy (1.81%). In addition, 275 cases of sensorineural hearing loss of unknown etiology accounted for 38.19% of the children surveyed.
Conclusions: Long-term follow-up is needed to detect delayed hearing impairment and auditory development in children. The need for long-term follow-up should be taken into account when designing an intervention strategy. Furthermore, the use of the deafness gene chip should further elucidate the etiology of neonatal hearing impairment.
  [Abstract] [Full Text] [PDF]  
Therapeutic response in children with ADHD: role of observers and settings
  Venkat Bhat, Sarojini M. Sengupta, Natalie Grizenko, Ridha Joober
Background: This study aims at characterizing the extent of correlation of treatment response (TR) obtained in various observation settings (home, school, clinic) by different observers (parents, teachers, clinicians).
Methods: Children with attention deficit hyperactivity disorder (ADHD) underwent a 2-week double-blind, randomized, cross-over clinical trial with methylphenidate and placebo, and various measures were obtained during the 2 weeks. Interrelationships of TR were examined using Pearson*s correlation coefficients.
Results: The study included 526 children (420 male, 106 female) with ADHD. TR between different observers shows a variable correlation between parents and teachers. No correlation is seen between parents/teacher evaluation of TR and laboratory-based measures (Continuous Performance Task; Restricted Academic Situation Scale).
Conclusion: The results firmly support the need to synthesize information from many sources in evaluating TR in ADHD.
  [Abstract] [Full Text] [PDF]  
World Journal of Pediatric Surgery
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