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。     

严重呼吸综合征患儿及密切接触者血清SARS相关冠状病毒抗体的检测分析

目的　了解严重急性呼吸综合征(severeacuterespiratorysyndrome ,SARS)患儿SARS相关冠状病毒(SARS CoV)特异性抗体水平和与SARS患儿密切接触的成人有无隐性感染。方法　采用间接免疫荧光(IFA)和ELISA两种方法检测北京市2 4例恢复期儿童SARS患者和2 6名与其密切接触的家长血清SARS CoV特异抗体,其中IFA法检测IgM和IgG抗体,ELISA检测IgM和混合抗体;同时通过入户问卷收集流行病学资料。结果　( 1 )IFA法测定血清SARS CoV IgG的阳性者1 0例( 4 2 % ) ,SARS CoV IgM阳性2例( 8% ) ;经ELISA法测定SARS CoV混合抗体的阳性者9例( 3 8% )。( 2 )流行病学资料显示抗体阳性的1 0例患儿中有明确SARS接触史的患儿8例,而在抗体阴性的1 3例中仅1例阳性(P <0 . 0 5)。( 3 ) 1位受检家长(患儿的祖母)IFA法检测SARS CoV IgG和ELISA法检测混合抗体均为阳性,约占4% ( 1 / 2 6) ,该患儿的祖父亦为SARS患者。结论　( 1 )有SARS接触史的患儿在抗体阳性组的比例较之在抗体阴性组的比例明显增高,提示流行病学史在儿科SARS临床诊断中具有重要价值。( 2 )未能证实与儿童SARS患者接触的成人中存在隐性感染。     

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     

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。     

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.     

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.     

The chronology of the 2002-2003 SARS mini pandemic

Severe acute respiratory syndrome (SARS) was a new human disease in the autumn of 2002. It first occurred in Southern China in November 2002 and was transported to Hong Kong on February 21, 2003 by an infected and ill patient. Ten secondary cases spread the infection to two hospitals in Hong Kong and to Singapore, Toronto and Hanoi. In March 2003 a novel coronavirus (SARS-CoV) was found to be the causative agent. Within 11 weeks from the first SARS case in Hong Kong it had spread to an additional 27 countries or special administrative regions. The mini pandemic peaked during the last week of May 2003 and the last new probable case was on July 13, 2003. There were a total of 8096 probable cases and 774 deaths. Sixty-six per cent of the cases occurred in China, 22% in Hong Kong, 4% in Taiwan and 3% in both Singapore and Canada. Twenty-one per cent of all cases occurred in healthcare workers.     

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.     

Chemokine response in children with SARS

The chemokine response of eight children with serologically confirmed severe acute respiratory syndrome (SARS) was longitudinally monitored. All had raised plasma interferon gamma inducible protein (IP-10) concentrations, which suggested an active type 1 T-helper lymphocyte mediated immune response. High circulating IP-10 levels could facilitate viral clearance and might play a role in assisting the recovery of the patients.     

Chemokine response in children with SARS.

The chemokine response of eight children with serologically confirmed severe acute respiratory syndrome (SARS) was longitudinally monitored. All had raised plasma interferon gamma inducible protein (IP-10) concentrations, which suggested an active type 1 T-helper lymphocyte mediated immune response. High circulating IP-10 levels could facilitate viral clearance and might play a role in assisting the recovery of the patients.     

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.     

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.     

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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。     

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。     

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.     

Epidemiologic linkage and public health implication of a cluster of severe acute respiratory syndrome in an extended family

Severe acute respiratory syndrome (SARS) is highly contagious. Mandatory home confinement of 10 days has generally been recommended to quarantine close contacts of SARS cases. We report the epidemiologic linkage of SARS within an extended family. The estimated incubation period was beyond 10 days in some of the affected members. One child was identified as the source of SARS transmission to another household.     

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。     

儿童COVID-19的临床特征：一项关于SARS、MERS及COVID-19的系统评价

目的 系统总结新型冠状病毒肺炎（COVID-19）儿童病例的临床特征。方法 计算机检索PubMed、Embase、Web of Science、The Cochrane Library、中国知网、重庆维普和万方数据库,搜集关于儿童COVID-19的临床研究,检索时限均为建库至2020年5月21日。由2名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,对纳入研究进行描述性分析。并与严重呼吸窘迫综合征（SARS）、中东呼吸综合征（MERS）儿童病例相关指标进行比较。结果 共纳入75个研究,包括COVID-19儿童病例806例。研究结果显示：患儿年龄在生后36?h到18岁不等,男女比例为1.21?：?1。与SARS、MERS病例类似,COVID-19病例最常见感染方式为家庭聚集感染,占74.6%（601/806）。COVID-19、SARS及MERS病例临床症状相似,以发热、咳嗽为主。部分患儿出现消化道症状。上述三者无症状感染儿童比例分别为17.9%（144/806）、2.5%（2/81）及57.1%（12/21）。COVID-19、MERS病例胸部影像学病变以双侧为主,病变阳性率分别为63.4%（421/664）及26.3%（5/19）,均低于其病毒核酸检测阳性率（分别为99.8%及100%）。而SARS病例胸部影像学以单侧病变为主,其影像学阳性率为88.9%（72/81）,高于病毒核酸检测阳性率（29.2%）。COVID-19及SARS患儿粪便中均检测到病毒核酸,检测阳性率分别为60.2%（56/93）、71.4%（5/7）。COVID-19患儿重症率及病死率分别为4.5%（31/686）、0.1%（1/806）;SARS儿童重症率及病死率分别为1.5%（1/68）、0%;MERS儿童重症率及病死率分别为14.3%（3/21）、9.5%（2/21）。结论 儿童COVID-19临床症状与儿童SARS、MERS相似,以发热、咳嗽为主,均存在无症状感染者,但COVID-19和SARS儿童的病情较MERS轻。家庭聚集感染为COVID-19儿童重要的感染方式。流行病学接触史、影像学检查及病毒核酸检测结果是诊断COVID-19的重要依据。