Severe acute respiratory syndrome (SARS) in children: epidemiology, presentation and management

Severe acute respiratory syndrome (SARS) is a newly recognised and highly contagious respiratory infection caused by a new strain of coronavirus. The disease can result in progressive respiratory failure in adults and the mortality rate has been reported to be 8-15%. This infection spreads by droplet transmission and children appear to acquire SARS through close household contact exposure to infected adults. Disease severity is, however, much milder in the paediatric age group. The common laboratory findings in infected children and adolescents include lymphopaenia and elevated levels of lactate dehydrogenase and creatinine phosphokinase. Air space consolidation is commonly seen during the course of the illness although chest radiographs are normal on presentation in half of the cases. The pathophysiology of SARS appears to be related to immunological dysregulation in response to the coronavirus infection. The optimal treatment of SARS in children remains to be determined. No case fatality in infected children has been reported. The early and proper isolation of infected adults, meticulous infection control measures in the hospital setting, exhaustive contact tracing and quarantine measures are important steps in preventing the spread of the disease among health care workers and into the community. The development of a sensitive and rapid test for early diagnosis is underway. Further controlled trials are necessary to define the optimal treatment of this infection in children.     

血清冠状病毒(变异株)特异性IgG抗体阳性患儿回顾性分析

目的　探讨儿童传染性非典型肺炎 (SARS)发生率低和症状轻的原因。方法　用酶联免疫吸附法 (ELISA)对2 0 0 1年及 2 0 0 3年 4～ 5月在首都儿科研究所门诊及住院的患儿血清标本 16 8份进行冠状病毒 (变异株 )特异性IgG抗体检测 ,并对住院患儿的临床表现进行回顾性分析。结果　 2 0 0 1年 77份血清标本 ,抗体阳性率为 4 1 6 % ;2 0 0 3年 4～ 5月 91份血清标本 ,阳性率为 39 6 %。对受检者中 10 2例曾经住院患儿临床表现的回顾性分析显示 ,抗体阳性与阴性患儿的临床表现及辅助检查结果无明显差别 ,抗体阳性患儿的临床诊断除肺炎外 ,还有上呼吸道感染、幼儿急疹、川崎病等。结论　冠状病毒 (变异株 )特异性IgG抗体阳性率有随年龄增长逐渐下降的趋势。在非SARS儿童中存在冠状病毒 (变异株 )特异性IgG抗体。     

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.     

Severe acute respiratory syndrome in children

BACKGROUND: Severe acute respiratory syndrome (SARS) is a febrile, respiratory tract illness caused by infection with the newly identified SARS-associated coronavirus. A notable feature of the 2003 global SARS outbreak was the relative paucity of cases reported among children. We reviewed the epidemiologic and clinical features of SARS in children and discuss implications of these findings for diagnosis, treatment and prevention of SARS. METHODS: We performed a literature search to identify reports of pediatric (younger than 18 years of age) patients meeting the World Health Organization case definitions for SARS and abstracted relevant clinical and epidemiologic information. RESULTS: We identified 6 case series reporting 135 pediatric SARS patients (80 laboratory-confirmed, 27 probable and 28 suspect) from Canada, Hong Kong, Taiwan and Singapore. Among laboratory-confirmed and probable SARS cases, the most common symptoms included fever (98%), cough (60%) and nausea or vomiting (41%); 97% had radiographic abnormalities. The clinical presentation of SARS in patients older than 12 years of age was similar to that in adults. However, patients 12 years of age or younger had milder disease and were less likely than older children to be admitted to an intensive care unit, receive supplemental oxygen or be treated with methylprednisolone. No deaths were reported among children or adolescents with SARS, and at 6 months after illness only mild residual changes were reported in exercise tolerance and pulmonary function. There is only 1 published report of transmission of SARS virus from a pediatric patient. CONCLUSIONS: Children and adolescents are susceptible to SARS-associated coronavirus infection, although the clinical course and outcome are more favorable in children younger than 12 years of age compared with adolescents and adults. Transmission of SARS from pediatric patients appears to be uncommon but is possible.     

北京地区部分儿童严重急性呼吸综合征的血清学研究

目的 确定临床诊断为严重急性呼吸综合征（SAILS）患儿感染的病原是否为SAILS相关冠状病毒（SAILS-CoV）;同时探讨儿童sARS患者的传播能力。方法2003年6-8月收集到的SAILS患者及其接触者血清标本177例,同时期的来源于非疫区择期手术儿童血清标本49例,以及无SAILS接触史的北京健康儿童血清标本93例,SAILS流行前儿童血清标本90例,总计409例。应用不同方法（包括酶联免疫吸附实验、间接免疫荧光、Western-blot等）、不同单位生产的试剂盒测定抗SAILS-CoV抗体。结果不同检测方法中,SAILS．CoV特异性IgG抗体阳性率在SAILS患儿中为39．1％-43．5％。成人SAILS患者中为57．1％-71．4％;与SAILS患儿接触的儿童中均为阴性。与SAILS患儿接触的成人中为6．0％-9．0％;与成人SAILS接触的儿童中为0-9．7％;与成人SAILS接触的成人中为4．4％-7．1％;同时期的正常儿童与非疫区择期手术儿童以及SAILS流行前的正常儿童血清标本用不同方法和试剂检测结果不尽相同。结论临床诊断为SAILS的患儿SAILS-CoV特异性IgG抗体阳性率（40％左右）明显低于临床诊断为SAILS的成人患者。提示在流行期间有相当一部分儿童sARS实际上是由其他的呼吸道病毒感染所致。与成人sARS接触的儿童和成人中,有一部分SAILS抗体为阳性,提示可能存在SAILS-CoV的隐性感染。目前已推广使用的SAILS诊断试剂对于儿童SAILS诊断的正确性还需要进一步的验证。     

儿童严重急性呼吸综合征血清流行病学特征初探

目的　了解儿童严重急性呼吸综合征 (SARS)患者SARS相关冠状病毒 (SARS CoV)特异抗体水平 ;初步调查与成人SARS患者密切接触的儿童 /成人及与SARS患儿密切接触的家长中隐性感染的情况。方法　 (1)采用间接免疫荧光 (IFA)和ELISA两种方法 ,对北京市恢复期儿童SARS患者 2 1例、与其密切接触的家长 2 3位、与SARS成人患者密切接触的儿童 2 4名和成人 34名 ,分别进行了SARS CoV特异抗体的检测 ,其中IFA检测IgG抗体 ,ELISA检测混合抗体。 (2 )通过入户问卷收集流行病学资料。结果　 (1)IFA测定SARS患儿血清SARS CoV IgG阳性者 8例 (38% ) ,同时经ELISA法测定SARS CoV混合抗体阳性者 7例 (33% )。 (2 )有SARS接触史的患儿在抗体阳性组中为 7/8,而在抗体阴性组中为 1/13。 (3)SARS患儿的家长中一位 (患儿的祖母 )经IFA检测SARS CoV IgG和ELISA法检测混合抗体为阳性 (1/2 3,4 % ) ,该患儿的祖父为SARS患者。 (4)对成人SARS患者的密切接触儿童调查结果为 :2 4份受检标本中 1份SARS CoV IgG阳性 (4% ) ;34份受检成人标本中 1份经IFA检测SARS CoV IgG和ELISA法检测混合抗体均为阳性 (3% )。 结论(1)临床诊断的儿童SARS患儿中有 38%经血清学证实为SARS CoV感染。(2 )流行病学资料显示 ,有SARS接触史的患儿在抗体阳性     

Severe acute respiratory syndrome (SARS) in neonates and children

Severe acute respiratory syndrome (SARS) runs a more benign course in children during the acute phase. Infants born to mothers with the disease did not acquire the infection through vertical transmission. The treatment strategy for children with SARS has not been standardised and is based on adult experience. Thus far, no deaths have been reported in the paediatric age group. Exercise impairment and residual radiological abnormalities were present six months after diagnosis. It is important to assess these patients on a regular basis to detect and provide appropriate management for any persistent or emerging long term sequelae in the physical, psychological, and social domains. This review describes the current understanding of SARS coronavirus infection in newborns and children.     

基因检测在儿童严重急性呼吸综合征疑似病例诊断中的应用

目的 通过病原学检测鉴别诊断严重急性呼吸综合征(SARS)。方法 对1例没有明确SARS接触史,入院时临床诊断疑为“支原体肺炎”的患儿进行病原学鉴别诊断。(1)对患儿的咽拭子标本进行常见呼吸道病毒(包括呼吸道合胞病毒、甲、乙型流感病毒、腺病毒和I、Ⅱ、Ⅲ型副流感病毒)的抗原检测。(2)用RT-PCR进行人类偏肺病毒、肠道病毒和鼻病毒的检测。(3)采用巢式RT-PCR方法,进行SARS病毒基因检测。根据WHO在网上公布的SARS冠状病毒复制酶基因1b区合成3对引物,其中I对为所有冠状病毒所保守的,用来进行第一次PCR,另2对为SARS冠状病毒所特异的,分别用于第二次PCR,这2对引物可分别扩增368和348bp的基因片段。结果 患儿咽拭子标本7种常见呼吸道病毒和人类偏肺病毒、肠道病毒和鼻病毒的检测结果均为阴性,而用不同引物对检测,SARS冠状病毒基因均为阳性。经测序显示,该基因片段与GenBank已公布的17株SARS冠状病毒的序列同源性为100％,而与人冠状病毒的标准株有很低的同源性。同时该患儿的恢复期血清SARS冠状病毒特异性IgM和IgG均为阳性。结论 从患儿标本中未检测到常见的7种呼吸道病毒、人类偏肺病毒、肠道病毒和鼻病毒,而检测到了SARS冠状病毒。经病原学检测,确诊患儿为SARS,,在SARS流行期间,用检测常见呼吸道病毒抗原或基因的方法,可以将儿科的急性呼吸道病毒感染与SAPS进行区别。     

严重急性呼唆综合征患儿血清抗严重急性呼吸综合征相关冠状病毒免疫球蛋白G远期随访

目的远期随访严重急性呼吸综合征（SARS）患儿血清中特异性抗SARS相关冠状病毒（CoV）IgG（SARS-CoV-IgG）抗体，并探讨其临床意义。方法儿童SAILS临床诊断病例16例和患儿的父母及与其密切接触家庭成员（其中包括7例SARS临床诊断病例、12例非SARS病例）19例。在SARS患儿病程1.5年左右，进行随访。采集患儿及其密切接触家庭成员外周静脉血2mL，常规分离血清。应用间接免疫荧光法（IFA）检测受试者血清中抗SARS-CoV-IgG抗体。结果16例儿童SAPS病例中，8例血清中抗SARS-CoV-IgG阳性，其中4例SARS患病期间抗SARS-CoV-IgM阳性，4例未查抗SARS-CoV-IgM抗体。另8例血清中抗SARS-CoV-IgG阴性，其中4例SAPS患病期间抗SARS-CoV-IgM阴性，4例未查抗SARS-CoV-IgM抗体。8例血清中抗SARS-CoV-IgG阳性的SARS患儿的8个家庭中均有2例及2例以上SARS患者。8例血清中抗SARS-CoV-IgG阴性的儿童SARS病例的8个家庭中均只有患儿本人为SARS患者。结论在病程1．5年后，实验室确诊的儿童SARS病例的血清中仍能检测到抗SARS-CoV-IgG抗体。家庭聚集发病是实验室确诊的SARS病例的一个重要特征。     

严重急性呼吸综合征患儿血清抗严重急性呼吸综合征相关冠状病毒免疫球蛋白G远期随访

目的远期随访严重急性呼吸综合征(SARS)患儿血清中特异性抗SARS相关冠状病毒(CoV)IgG(SARS-CoV-IgG)抗体,并探讨其临床意义。方法儿童SARS临床诊断病例16例和患儿的父母及与其密切接触家庭成员(其中包括7例SARS临床诊断病例、12例非SARS病例)19例。在SARS患儿病程1.5年左右,进行随访。采集患儿及其密切接触家庭成员外周静脉血2 mL,常规分离血清。应用间接免疫荧光法(IFA)检测受试者血清中抗SARS-CoV-IgG抗体。结果16例儿童SARS病例中,8例血清中抗SARS-CoV-IgG阳性,其中4例SARS患病期间抗SARS-CoV-IgM阳性,4例未查抗SARS-CoV-IgM抗体。另8例血清中抗SARS-CoV-IgG阴性,其中4例SARS患病期间抗SARS-CoV-IgM阴性,4例未查抗SARS-CoV-IgM抗体。8例血清中抗SARS-CoV-IgG阳性的SARS患儿的8个家庭中均有2例及2例以上SARS患者。8例血清中抗SARS-CoV-IgG阴性的儿童SARS病例的8个家庭中均只有患儿本人为SARS患者。结论在病程1.5年后,实验室确诊的儿童SARS病例的血清中仍能检测到抗SARS-CoV-IgG抗体。家庭聚集发病是实验室确诊的SARS病例的一个重要特征。     

The widening scope of coronaviruses

PURPOSE OF REVIEW: In the past 2 years, at least three distinct human coronaviruses have been discovered, including the etiological agent associated with severe acquired respiratory syndrome (SARS). These recently discovered viruses, with the exception of the SARS associated coronavirus (SARS-CoV), are likely to be common respiratory viruses and may be responsible for a substantial proportion of respiratory tract disease. RECENT FINDINGS: The SARS-CoV first appeared in 2002 and spread rapidly around the globe. Although the worldwide spread of SARS-CoV may have been halted, the emergence of this new virus demonstrates the potential threat represented by species-to-species transmission of coronaviruses. NL63, initially isolated from a young child with lower respiratory tract disease, represents a group of newly described group I coronaviruses that have been identified worldwide, which are associated with both upper and lower respiratory tract disease, particularly in young children. The distribution of HKU1, a newly identified group II coronavirus, is not yet established. NL63 and HKU1 are related to the common human coronaviruses 229E and OC43, respectively. SUMMARY: The discovery of at least three new human coronaviruses represents significant advances in the investigation of human respiratory tract disease. Further studies are required to fully define the impact of these new pathogens.     

A young infant with severe acute respiratory syndrome

Severe acute respiratory syndrome (SARS), a new contagious respiratory disease associated with a novel coronavirus, has spread worldwide and become a global health concern after its first outbreak in Guangdong Province of the People's Republic of China in November 2002. The clinical presentation and the radiologic, hematologic, biochemical, and microbiologic findings of a 56-day-old male infant with SARS are described. Some clinical and laboratory features are similar to those reported in adult and pediatric patients. However, this infant had a more severe clinical course as compared with the older children. This is the youngest patient with symptomatic SARS reported to date.     

非严重急性呼吸道综合征人群抗SARS冠状病毒特异性IgG的检测及分析

目的 研究非严重急性呼吸道综合征(SARS)人群血清中是否存在抗SARS冠状病毒特异性IgG。方法 研究对象为4组:第1组为2002年非SARS患儿88例(2002年备存血清);第2组为2003年SARS流行期间非SARS患儿89例;第3组为某SARS定点医院一线医务人员65例,均在SARS临床一线工作1个月;第4组为北京儿童医院非SARS一线工作人员33例。所用方法为间接ELISA法。结果 第1组抗SARS冠状病毒的特异性IgG检出率为19.1%,第2组为12.5%,两组差异没有显著性意义(P>0.05)。第3组和第4组抗SARS冠状病毒的特异性IgG检出率分别为1.54%和3.03%,两组差异也没有显著性意义(P>0.05)。若分别将第1组和第2组合并、第3组和第4组合并进行比较,则儿童组抗SARS冠状病毒的特异性IgG检出率为15.82%,成人组为2%,两组差异有非常显著性意义(P<0.01)。另外,把儿童研究对象按年龄分为3组:<1岁、～6岁、>6岁,<1岁年龄组抗SARS冠状病毒的特异性IgG检出率达36.36%,其余两组分别为8.77%和9.21%;<1岁年龄组的检出率与其余两组相比,差异均有显著性意义,P<0.01和P<0.01。结论 非SARS儿童血清中可检测出抗SARS冠状病毒特异性IgG,其检出率为15.82%,其中<1岁年龄组抗SARS冠状病毒特异性IgG的检出率达36.36%。但该特异性IgG产生的原因及意义有待进一步研究。     

Severe acute respiratory syndrome (SARS)

Several cases of life threatening respiratory disease with no identifiable cause were reported from Guangdong Province, China; these were soon followed by reports from many other countries. The disease was named as severe acute respiratory syndrome (SARS). A novel coronavirus, isolated from the respiratory secretions of patients, has been implicated in the causation of SARS. The modes of transmission include droplet spread, close contact, and Fomites; shedding of virus from respiratory tract is the primary mode of transmission. SARS clinically presents with high-grade fever, chills and rigors, myalgia, headache, cough with or without sputum production, dyspnea, and dizziness. Chest radiographs reveal unilateral or bilateral, predominantly peripheral, areas of consolidation progressing with in a short time of bilateral patchy consolidation. Preliminary reports suggest a milder illness in young children. The case definition of probable SARS cases, laboratory investigations and precautions for prevention of spread are discussed.     

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。     

SARS-CoV-2 infection in children – Understanding the immune responses and controlling the pandemic

In December 2019, a cluster of patients with severe pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in the city of Wuhan, China. The disease is now termed coronavirus disease 2019 (COVID-19). In the early reports, the patients were mainly middle-aged and elderly men, and children appeared to be less susceptible to this infection. With modern and efficient transportation, the disease quickly spread to almost all corners of the world and the mortality far exceeds that caused by severe acute respiratory syndrome (SARS) coronavirus or Middle East respiratory syndrome (MERS) coronavirus. As the number of children with COVID-19 gradually increases, the disease has been documented in premature babies, infants, children, and adolescents. Severe and fatal cases in children are relatively rare. The burden of disease in children has been relatively low, but the high proportions of asymptomatic or mildly symptomatic infections in children deserve careful attention. A clear understanding of the immune responses to the virus in children and the transmission potential of asymptomatic children is of paramount importance for the development of specific treatments and vaccine in order to effectively control the ongoing pandemic.     

A case-control study of SARS versus community acquired pneumonia

The clinical, laboratory, and radiological features at presentation of 16 children (<12 years) with severe acute respiratory syndrome (SARS) and pneumonia were compared with 32 age matched patients with community acquired pneumonia for determination of predictive factors that could allow early differentiation of the two conditions. A definitive contact history was the most important predictor for SARS. Raised serum lactate dehydrogenase concentration in the presence of low neutrophil count and serum creatine phosphokinase level at presentation also indicated an increased likelihood of SARS-coronavirus infection in young children.     

A case-control study of SARS versus community acquired pneumonia.

The clinical, laboratory, and radiological features at presentation of 16 children (<12 years) with severe acute respiratory syndrome (SARS) and pneumonia were compared with 32 age matched patients with community acquired pneumonia for determination of predictive factors that could allow early differentiation of the two conditions. A definitive contact history was the most important predictor for SARS. Raised serum lactate dehydrogenase concentration in the presence of low neutrophil count and serum creatine phosphokinase level at presentation also indicated an increased likelihood of SARS-coronavirus infection in young children.     

SARS in newborns and children

The severe acute respiratory syndrome (SARS) is a highly contagious infection caused by a newly discovered strain of coronavirus (SARS-CoV). Infants born to pregnant women with SARS did not appear to acquire the infection through vertical transmission. Some newborn infants, however, developed severe intrauterine growth retardation and life-threatening gastrointestinal complications. It is now known that the clinical course and prognosis are different between paediatric and adult SARS patients. Young children (< 12 years), in general, run a less aggressive clinical course than do teenage and adult patients. Thus far, no fatalities have been reported in the paediatric age group (< or =18 years). This review describes the current understanding of the clinical manifestations, diagnostic tests, immunological profiles, patient management and outcomes of SARS-CoV infection in the paediatric population.