Convalescent plasma for pediatric patients with SARS‐CoV‐2‐associated acute respiratory distress syndrome

There are no proven safe and effective therapies for children who develop life‐threatening complications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Convalescent plasma (CP) has demonstrated potential benefit in adults with SARS‐CoV‐2, but has theoretical risks.We present the first report of CP in children with life‐threatening coronavirus disease 2019 (COVID‐19), providing data on four pediatric patients with acute respiratory distress syndrome. We measured donor antibody levels and recipient antibody response prior to and following CP infusion. Infusion of CP was not associated with antibody‐dependent enhancement (ADE) and did not suppress endogenous antibody response. We found CP was safe and possibly efficacious. Randomized pediatric trials are needed.     

School closure,COVID‐19 and lunch programme: Unprecedented undernutrition crisis in low‐middle income countries

The coronavirus disease 2019 pandemic has affected nearly 70% of children and teenagers around the world due to school closure policies. School closure is implemented widely in order to prevent viral transmission and its impact on the broader community, based on preliminary recommendations and evidence from influenza. However, there is debate with regard to the effectiveness of school closures. Growing evidence suggests that a child's SARS‐CoV‐2 infection is often mild or asymptomatic and that children may not be major SARS‐CoV‐2 transmitters; thus, it is questionable if school closures prevent transmission significantly. This question is important as a majority of children in low‐ and middle‐income countries depend on free school meals; unexpected long‐term school closure may adversely impact nutrition and educational outcomes. Food insecurity is expected to be higher during the pandemic. In this viewpoint, we argue for a more thorough exploration of potential adverse impacts of school closures in low‐ and middle‐income countries and recommend actions to ensure that the health and learning needs of vulnerable populations are met in this time of crisis.     

SARS‐CoV‐2 and human milk: What is the evidence?

The novel coronavirus SARS‐CoV‐2 has emerged as one of the most compelling and concerning public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical and public health communities has rapidly engaged to collectively find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS‐CoV‐2 transmission. Although respiratory droplets are a known mechanism of transmission, other mechanisms are likely. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS‐CoV‐2) via human milk and/or breastfeeding. Results of the literature search reported here (finalized on 17 April 2020) revealed a single study providing some evidence of vertical transmission of human coronavirus 229E; a single study evaluating presence of SARS‐CoV in human milk (it was negative); and no published data on MERS‐CoV and human milk. We identified 13 studies reporting human milk tested for SARS‐CoV‐2; one study (a non‐peer‐reviewed preprint) detected the virus in one milk sample, and another study detected SARS‐CoV‐2 specific IgG in milk. Importantly, none of the studies on coronaviruses and human milk report validation of their collection and analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS‐CoV‐2) during breastfeeding are discussed.     

Child protection in the time of COVID‐19

As the number of cases of coronavirus disease 2019 (COVID‐19) caused by the virus SARS‐CoV‐2 rises exponentially in Australia with consequences for the health system and society at large, we need to remember that during this pandemic that necessary social distancing measures, effective school closures and rising unemployment levels may lead to an increased risk for child abuse and neglect.     

儿童新型冠状病毒感染诊断、治疗和预防专家共识(第四版)北大核心CSCD

自2019年12月以来,新型冠状病毒(SARS-CoV-2)感染在全球肆虐已2年余。我国始终采取科学有效的防控措施并取得一定成功,但随着SARS-CoV-2的不断变异和境外输入病例,导致疫情防控工作更加艰巨、复杂。随着变异株的变化,儿童病例数量也出现了变化,并且出现了一些新的特殊症候和并发症,这为我国儿童SARS-CoV-2感染的防治提出了新的课题。本共识在《儿童新型冠状病毒感染诊断、治疗和预防专家共识(第三版)》的基础上,根据新变异株的特点,对其病原学、病理学、发病机制等进行阐述,总结儿童病例的临床特点和诊疗经验,就儿童病例实验室检查、诊断、治疗和防控等提出建议,为进一步加强对我国儿童SARS-CoV-2感染的防治提供参考。     

PSTPIP1‐associated myeloid‐related proteinemia inflammatory syndrome: A rare cause of childhood neutropenia associated with systemic inflammation and hyperzincemia

Neutropenia in pediatric patients can be due to a variety of disorders. We describe two patients who underwent extensive evaluation over many years for arthralgias and moderate neutropenia of unclear etiology. Genetic testing identified a pathogenic variant in PSTPIP1 (proline‐serine‐threonine phosphatase‐interacting protein 1) in both patients. Markedly elevated inflammatory markers and zinc levels confirmed the rare diagnosis of PSTPIP1‐associated myeloid‐related proteinemia inflammatory (PAMI) syndrome, tailoring treatment. Neutropenia is common in patients with PAMI syndrome. Unique mutations seen in PAMI syndrome may account for the specific phenotypic features of this disorder.     

Acute chest syndrome in the setting of SARS‐COV‐2 infections—A case series at an urban medical center in the Bronx

New York City has emerged as one of the epicenters of the SARS‐COV‐2 pandemic, with the Bronx being disproportionately affected. This novel coronavirus has caused significant respiratory manifestations raising the concern for development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD). We report a series of pediatric SCD SARS‐COV‐2‐positive patients admitted with ACS. SARS‐COV‐2‐positive SCD patients, who did not develop ACS, were the comparison group. Hydroxyurea use (P‐value = .02) and lower absolute monocyte counts (P‐value = .04) were noted in patients who did not develop ACS. These preliminary findings need to be further evaluated in larger cohorts.     

SARS: future research and vaccine

Severe acute respiratory syndrome (SARS) is a new infectious disease of the 21st century that has pandemic potential. A novel coronavirus (CoV) was identified as its aetiological agent and its genome was sequenced within months of the World Health Organisation issuing a global threat on SARS. The high morbidity and mortality of this potentially pandemic infection demands a rapid research response to develop effective antiviral treatment and vaccine. This will depend on understanding the pathogenesis and immune response to SARS CoV. Further understanding of the ecology of SARS CoV in human and animals will help prevent future cross species transmission. Likewise for the super-spreading events, clarification of the underlying reasons will be important to prevent a large scale outbreak of SARS. Lastly it is of utmost importance that international research collaboration should be strengthened to deal with SARS and any other emerging infectious disease that can seriously threaten our future.     

Kawasaki disease fact check: Myths,misconceptions and mysteries

Kawasaki disease (KD) is an important cause of childhood vasculitis and a common cause of acquired heart disease in children world‐wide. The emergence of Paediatric Multisystem Inflammatory Syndrome‐Temporally Associated with SARS‐CoV‐2, a KD‐like hyperinflammatory syndrome and the recent death of Dr Tomisaku Kawasaki make this a timely review. Although KD was described by Dr Kawasaki over 50 years ago, there is still no specific diagnostic test and the aetiology remains elusive. This article summarises the latest evidence, highlights important myths and misconceptions and discusses some of the mysteries that surround this disease.     

The COVID‐19 pandemic: A rapid global response for children with cancer from SIOP,COG, SIOP‐E,SIOP‐PODC,IPSO, PROS,CCI, and St Jude Global

The COVID‐19 pandemic is one of the most serious global challenges to delivering affordable and equitable treatment to children with cancer we have witnessed in the last few decades. This Special Report aims to summarize general principles for continuing multidisciplinary care during the SARS‐CoV‐2 (COVID‐19) pandemic. With contributions from the leadership of the International Society for Pediatric Oncology (SIOP), Children's Oncology Group (COG), St Jude Global program, and Childhood Cancer International, we have sought to provide a framework for healthcare teams caring for children with cancer during the pandemic. We anticipate the burden will fall particularly heavily on children, their families, and cancer services in low‐ and middle‐income countries. Therefore, we have brought together the relevant clinical leads from SIOP Europe, COG, and SIOP‐PODC (Pediatric Oncology in Developing Countries) to focus on the six most curable cancers that are part of the WHO Global Initiative in Childhood Cancer. We provide some practical advice for adapting diagnostic and treatment protocols for children with cancer during the pandemic, the measures taken to contain it (e.g., extreme social distancing), and how to prepare for the anticipated recovery period.     

5岁以下儿童新型冠状病毒感染的免疫预防最新进展北大核心CSCD

免疫预防是指应用免疫学的方法增强机体特异性免疫力,从而达到预防疾病的策略,按其获得方式可分为主动免疫(主要是接种疫苗)和被动免疫(包括母传抗体)。目前,疫苗接种是预防和控制新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)最为有效的措施。近期,美国、哥斯达黎加和澳大利亚已批准可为6个月以上儿童接种新型冠状病毒疫苗以提供主动免疫保护,并有临床试验证实孕妇接种新型冠状病毒疫苗可为6个月以下婴儿提供被动免疫保护,这预示着有望实现COVID-19免疫预防策略的全年龄人群覆盖。     

Progressive subglottic stenosis in a child with Pallister‐Killian syndrome

Pallister‐Killian syndrome (PKS) is rare genetic disorder caused by tetrasomy 12p mosaicism with supernumerary isochromosome 12p that manifests with intellectual disability, craniofacial dysmorphism, and epilepsy. Although PKS presents as a multisystem morphological defect, respiratory system involvement is rare, except for diaphragmatic hernia. We are the first to report a case of PKS with progressive subglottic stenosis. Subglottic stenosis is a potentially lethal condition due to severe respiratory obstruction and difficult intubation; therefore, further accumulation of cases is required to assess the causal link between PKS and subglottic stenosis.     

Paraneoplastic opsoclonus myoclonus syndrome associated with inflammatory myofibroblastic tumor in a pediatric patient

Opsoclonus myoclonus syndrome (OMS) is a rare neurological syndrome caused by a paraneoplastic autoimmune process that affects children with neuroblastic tumors. Treatment includes corticosteroids, intravenous gamma globulin (IVIG), rituximab, and other immunosuppressive therapies. Here, we describe a patient diagnosed with OMS associated with a localized inflammatory myofibroblastic tumor. The patient has no evidence of tumor recurrence following surgical resection with 8‐month follow‐up. The neurologic symptoms resolved with corticosteroids and IVIG. This case demonstrates that in children, neoplasms other than neuroblastoma may be associated with this paraneoplastic syndrome, and highlights the importance of evaluating patients with OMS for underlying malignancies.     

When separation is not the answer: Breastfeeding mothers and infants affected by COVID‐19

The World Health Organization (WHO) has provided detailed guidance on the care of infants of women who are persons under investigation (PUI) or confirmed to have COVID‐19. The guidance supports immediate post‐partum mother–infant contact and breastfeeding with appropriate respiratory precautions. Although many countries have followed WHO guidance, others have implemented infection prevention and control (IPC) policies that impose varying levels of post‐partum separation and discourage or prohibit breastfeeding or provision of expressed breast milk. These policies aim to protect infants from the potential harm of infection from their mothers, yet they may fail to fully account for the impact of separation. Global COVID‐19 data are suggestive of potentially lower susceptibility and a typically milder course of disease among children, although the potential for severe disease in infancy remains. Separation causes cumulative harms, including disrupting breastfeeding and limiting its protection against infectious disease, which has disproportionate impacts on vulnerable infants. Separation also presumes the replaceability of breastfeeding—a risk that is magnified in emergencies. Moreover, separation does not ensure lower viral exposure during hospitalizations and post‐discharge, and contributes to the burden on overwhelmed health systems. Finally, separation magnifies maternal health consequences of insufficient breastfeeding and compounds trauma in communities who have experienced long‐standing inequities and violence, including family separation. Taken together, separating PUI/confirmed SARS‐CoV‐2‐positive mothers and their infants may lead to excess preventable illnesses and deaths among infants and women around the world. Health services must consider the short‐andlong‐term impacts of separating mothers and infants in their policies.     

Breastfeeding and coronavirus disease‐2019: Ad interim indications of the Italian Society of Neonatology endorsed by the Union of European Neonatal & Perinatal Societies

The recent COVID‐19 pandemic has spread to Italy with heavy consequences on public health and economics. Besides the possible consequences of COVID‐19 infection on a pregnant woman and the fetus, a major concern is related to the potential effect on neonatal outcome, the appropriate management of the mother–newborn dyad, and finally the compatibility of maternal COVID‐19 infection with breastfeeding. The Italian Society on Neonatology (SIN) after reviewing the limited scientific knowledge on the compatibility of breastfeeding in the COVID‐19 mother and the available statements from Health Care Organizations has issued the following indications that have been endorsed by the Union of European Neonatal & Perinatal Societies (UENPS). If a mother previously identified as COVID‐19 positive or under investigation for COVID‐19 is asymptomatic or paucisymptomatic at delivery, rooming‐in is feasible, and direct breastfeeding is advisable, under strict measures of infection control. On the contrary, when a mother with COVID‐19 is too sick to care for the newborn, the neonate will be managed separately and fed fresh expressed breast milk, with no need to pasteurize it, as human milk is not believed to be a vehicle of COVID‐19. We recognize that this guidance might be subject to change in the future when further knowledge will be acquired about the COVID‐19 pandemic, the perinatal transmission of SARS‐CoV‐2, and clinical characteristics of cases of neonatal COVID‐19.     

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目的了解北京地区儿童严重急性呼吸道综合征(SARS)病例的临床特征和远期随访结果。方法截止2003-07-10,首都医科大学附属北京儿童医院SARS医疗小组收治的以及北京市卫生局科教处提供的北京地区儿童SARS病例共38例,根据卫生部SARS信息系统提供的临床信息总结分析儿童SARS病例的临床特征,在患儿出院后1年半左右,对38例患儿进行随访研究,随访的内容包括:(1)血压测量;(2)血常规检测;(3)肝肾功能检测;(4)肺:所有患儿进行X线胸片和肺功能检测,若二者之一有异常,则进一步进行高分辨CT检测;(5)股骨头X片;(6)心电图和心脏B超;(7)T细胞亚群检测;(8)患儿行为和主观生活质量评估,包括儿少主观生活质量和儿童行为量表;(9)血清冠状病毒特异性IgG抗体检测。结果38例儿童SARS临床表现中,发热率为100%,咳嗽30例(78·9%),咳痰25例(65·8%),气促3例(7·9%),全身中毒症状中,乏力、肌肉关节酸痛和头痛的发生率分别是36·4%、7·9%和18·4%。从实验室检测看,38例儿童SARS中,外周血白细胞<4·0×109/L者8例(21·1%),(4·4~10·0)×109/L者25例(65·8%),>10·0×109/L者5例(13·2%)。血小板减少2例(5·26%)。部分病例肝肾功能和心肌酶轻度异常。共有16例儿童SARS病例家长按期完成随访研究。16病例中,血清抗SARS-CoV-IgG阳性和阴性各8例。血清抗SARS-CoV-IgG阴性和阳性病例的临床特征症状差异无显著性意义。患儿的心肝肾功能、股骨头X片、T细胞亚类均正常,无高血压病例。3例患儿肺功能检查均示轻度异常,表现为FEF50-75轻度减低,R20轻度升高,其中1例行高分辨CT检查,结果正常。共有8例8岁以上患儿进行了儿童行为调查和儿少主观生活质量评估,未见明显的心理和行为障碍存在。结论SARS在儿童并不是一个严重的疾病,其临床表现轻、预后好,远期没有严重的并发症。但其原因还需要进一步研究。     

免疫抑制儿童感染新型冠状病毒Omicron变异株病毒清除时间的回顾性队列研究

背景：儿童新型冠状（新冠）病毒Omicron变异株流行期间，免疫抑制状态儿童新冠病毒清除时间定量分析研究较少。 目的：探讨新冠病毒Omicron株感染后免疫抑制和非免疫抑制儿童病毒清除的时间差别，为公共卫生政策制定和精准疫情防控措施提供临床数据。 设计：回顾性队列研究。 方法：以新冠病毒Omicron变异株感染住院患儿为队列人群，分为免疫抑制组和非免疫抑制组，免疫抑制分为绝对免疫抑制、相对免疫抑制和实施免疫抑制疗法，以免疫抑制组病例的性别、年龄和新冠病毒感染的分型与非免疫抑制组行1∶3匹配。以鼻咽拭子新冠病毒PCR检测拷贝数阈（Ct）值≥35为队列终点。 主要结局指标：新冠病毒清除时间。 结果：2022年4月12日至2022年5月12日在上海市新冠病毒感染定点收治医院符合本文共同纳入和排除标准的连续病例728例。免疫抑制组33例，其中绝对免疫抑制8例，相对免疫抑制23例，接受免疫抑制疗法2例（不包括绝对和相对免疫抑制患儿）。非免疫抑制组匹配后99例。2组临床症状、新冠病毒感染治疗和疫苗接种次数差异均无统计学意义。免疫抑制组和非免疫抑制组新冠病毒清除时间分别为（16.5±6.8）和（10.3±4.4）d，差异有统计学意义。免疫抑制组和非免疫抑制组新冠病毒感染轻型病例病毒清除时间分别为（14.0 ± 8.3）和（9.7 ± 3.1）d，普通型病例病毒清除时间分别为（18.3 ± 4.9）和（11.2 ± 5.9）d，差异均有统计学意义。2组单日病毒清除率在第9~14天时差异有统计学意义（P为0.005~0.039）。2组普通型病例单日病毒清除率在第10~15天时差异有统计学意义。免疫抑制组新冠病毒感染2周后核酸检测再次呈阳性3例（9%），临床分型均较前轻，3例均未接种新冠疫苗。 结论：Omicron株感染的免疫抑制患儿病毒清除时间较非免疫抑制患儿显著延长，主要反映在第9~14天，免疫抑制患儿病毒复阳风险高，提示需要更长的隔离时间和转阴后严格的病毒监测。     

Therapeutic interventions for fetal inflammatory response syndrome (FIRS)

Fetal inflammatory response syndrome (FIRS) is a condition defined by systemic inflammation in the fetus, a rapid increase of pro-inflammatory cytokines into the fetal circulation (including interleukin-1 and interleukin-6), as well as a cellular response (such as increased neutrophils, monocyte/macrophages, and T cells) and the presence of funisitis. FIRS can lead to death and multisystem organ damage in the fetus and newborn. Brain injuries and subsequent risk of cerebral palsy and cognitive impairments are the most threatening long-term complications. This paper reviews the definition of FIRS, summarizes its associated complications, briefly describes the available methods to study FIRS, and discusses in more detail the potential therapeutic candidates that have been so far studied to protect the fetus/newborn from FIRS and to alleviate its associated complications and sequelae.     

Documento español de consenso sobre diagnóstico,estabilización y tratamiento del síndrome inflamatorio multisistémico pediátrico vinculado a SARS-CoV-2 (SIM-PedS)

A new paediatric multisystem inflammatory syndrome, linked to SARS-CoV-2, has been described. The clinical picture is variable and is associated with an active or recent infection due to SARS-CoV-2. A review of the existing literature by a multidisciplinary group of paediatric specialists is presented in this document. Later, they make recommendations on the stabilisation, diagnosis, and treatment of this syndrome.     

Multisystem inflammatory disease in neonates (MIS-N) due to maternal COVID-19

Multisystem inflammatory disease in neonates (MIS-N) is a disease of immune dysregulation presenting in the newborn period. Thouvgh its etiopathogenesis is proposed to be similar to multisystem inflammatory disease in Children (MIS-C), the exact pathophysiology is largely unknown as of present. The definition of MIS-N is contentious. The evidence for its incidence, the clinical features, profile of raised inflammatory markers, treatment strategies and outcomes stem from case reports, case series and cohort studies with small sample sizes. Though the incidence of MIS-N in severe acute respiratory syndrome caused by the coronavirus CoVID-2 (SARS-CoV-2) infected asymptomatic neonates is low, its incidence in symptomatic neonates is relatively higher. Further, amongst the neonates who are treated as MIS-N, the mortality rate is high. The review also evaluates the various other unresolved aspects of MIS-N from limited published literature and identifies knowledge gaps which could be areas of future research.