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.     

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-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.     

Severe acute respiratory syndrome (SARS): chest radiographic features in children

Background Severe acute respiratory syndrome (SARS) is a recently recognized condition of viral origin associated with substantial morbidity and mortality rates in adults. Little information is available on its radiologic manifestations in children.Objective The goal of this study was to characterize the radiographic presentation of children with SARS.Materials and methods We abstracted data (n=62) on the radiologic appearance and course of SARS in pediatric patients with suspect (n=25) or probable (n=37) SARS, diagnosed in five hospital sites located in three cities: Toronto, Singapore, and Hong Kong. Available chest radiographs and thoracic CTs were reviewed for the presence of the following radiographic findings: airspace disease, air bronchograms, airways inflammation and peribronchial thickening, interstitial disease, pleural effusion, and hilar adenopathy.Results A total of 62 patients (suspect=25, probable=37) were evaluated for SARS. Patient ages ranged from 5.5 months to 17 years and 11.5 months (average, 6 years and 10 months) with a female-to-male ratio of 32:30. Forty-one patients (66.1%) were in close contact with other probable, suspect, or quarantined cases; 10 patients (16.1%) had recently traveled to WHO-designated affected areas within 10 days; and 7 patients (11.2%) were transferred from other hospitals that had SARS patients. Three patients, who did not have close/hospital contact or travel history to affected areas, were classified as SARS cases based on their clinical signs and symptoms and on the fact that they were living in an endemic area. The most prominent clinical presentations were fever, with a temperature over 38 °C (100%), cough (62.9%), rhinorrhea (22.6%), myalgia (17.7%), chills (14.5%), and headache (11.3%). Other findings included sore throat (9.7%), gastrointestinal symptoms (9.7%), rigor (8.1%), and lethargy (6.5%). In general, fever and cough were the most common clinical presentations amongst younger pediatric SARS cases (age<10 years), whereas, in addition to these symptoms, headache, myalgia, sore throat, chills, and/or rigor were common in older patients (age10 years). The chest radiographs of 35.5% of patients were normal. The most prominent radiological findings that were observed in the remaining patients were areas of consolidation (45.2%), often peripheral with multifocal lesions in 22.6%. Peribronchial thickening was noted on chest radiographs of 14.5% of patients. Pleural effusion was observed only in one patient (age 17 years and 11.5 months), whereas interstitial disease was not observed in any patient.Conclusion In pediatric cases, SARS manifests with nonspecific radiographic features making radiological differentiation difficult, especially from other commonly encountered childhood respiratory viral illnesses causing airspace disease. The radiographic presentation of suspected SARS cases ranged from normal to mild perihilar peribronchial thickening. The radiographic presentations, as expected, were relatively more pronounced in the SARS probable cases.     

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.     

Bird flu: lessons from SARS

Severe acute respiratory syndrome (SARS) and avian influenza are two important newly emerged infections with pandemic potential. Both infections have crossed the species barrier to infect humans. SARS originated from southern China and spread to many countries in early 2003. The close collaboration of scientists around the world resulted in a rapid identification of the causative agent, and the early isolation of infected cases and meticulous infection control measures were the key to successfully controlling the outbreak of SARS. The first outbreak of human cases of avian influenza was reported in 1997 in Hong Kong. Since 2003, there have been many small outbreaks of human cases around the world, and the reported mortality is greater than 50%. Current evidence suggests that the human-to-human transmission of avian influenza is rather inefficient, but mutation might occur in the future resulting in improved transmission and possibly a pandemic in humans. As with the outbreak of SARS, the development of sensitive and accurate early diagnostic tests is extremely important for successful control of the outbreak at source. The availability of isolation facilities, the stockpiling of antiviral agents and effective and safe vaccination will be extremely important in minimising the damage of a new influenza pandemic.     

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.     

Severe acute respiratory syndrome (SARS) in a paediatric cluster in Singapore

Background Severe acute respiratory syndrome (SARS) is a major infectious disease pandemic that occurred in early 2003, and one of the diagnostic criteria is the presence of chest radiographic findings.Objective To describe the radiographic features of SARS in a cluster of affected children.Materials and methods The chest radiographs of four related children ranging in age from 18 months to 9 years diagnosed as having SARS were reviewed for the presence of air-space shadowing, air bronchograms, peribronchial thickening, interstitial disease, pleural effusion, pneumothorax, hilar lymphadenopathy and mediastinal widening.Results Ill-defined air-space shadowing was the common finding in all the children. The distribution was unifocal or multifocal. No other findings were seen on the radiographs. None of the children developed radiographic findings consistent with acute respiratory distress syndrome. All four children showed significant resolution of the radiographic findings 4–6 days after the initial radiograph.Conclusions Early recognition of these features is important in implementing isolation and containment measures to prevent the spread of infection. SARS in children appears to manifest as a milder form of the disease as compared to adults.     

Epidemiology of severe acute respiratory syndrome (SARS): adults and children

Severe acute respiratory syndrome (SARS) is a newly described respiratory infection with pandemic potential. The causative agent is a new strain of coronavirus most likely originating from wild animals. This disease first emerged in November 2002 in Guangdong Province, China. Early in the outbreak the infection had been transmitted primarily via household contacts and healthcare settings. In late February 2003 the infection was transmitted to Hong Kong when an infected doctor from the mainland visited there. During his stay in Hong Kong at least 17 guests and visitors were infected at the hotel at which he stayed. By modern day air travel, the infection was rapidly spread to other countries including Vietnam, Singapore and Canada by these infected guests. With the implementation of effective control strategies including early isolation of suspected cases, strict infection control measures in the hospital setting, meticulous contact tracing and quarantine, the outbreak was finally brought under control by July 2003. In addition, there were another two events of SARS in China between the end of December 2003 and January 2004 and from March to May 2004; both were readily controlled without significant patient spread.     

Diarrhoea as the presenting sign in an adolescent suffering from severe acute respiratory syndrome

Patients with severe acute respiratory syndrome (SARS) may present with extra-pulmonary symptoms. We report a 16-year-old adolescent with SARS who presented with diarrhoea. Treatment directed against SARS was prompted by an epidemiological link and the clinical picture as the disease evolved. This atypical presentation posed a diagnostic challenge for physicians. Conclusion:Proper disposal of patient excreta is important to prevent the spread of severe acute respiratory syndrome.     

广州地区33例儿童严重急性呼吸综合征临床特点和治疗转归

目的　分析儿童严重急性呼吸综合征 (SARS)的临床特点及治疗转归。方法　分析2 0 0 3年春广州地区 33例SARS的临床症状、体征、实验室检查、治疗、病情经过及转归。结果　 33例中有明确SARS接触史者 5例 (1 5 % ) ,5例 (1 5 % )患儿患病后其密切接触者出现发热和 (或 )咳嗽。SARS病例 3～ 1 2岁儿童占 82 %。主要表现为发热 (1 0 0 % )和咳嗽 (91 % ) ,多为高热、干咳。外周血白细胞总数 (2 5～ 9 7)× 1 0 9/L ,以淋巴细胞为主者 1 8例。外周血白细胞总数 <5 0× 1 0 9/L者 2 2例 (67% ) ;外周血白细胞总数 (5 0～ 7 0 )× 1 0 9/L者 1 0例 (30 % )。肺部细湿 1 9例 (58% ) ,肺部无音者 1 4例 (42 % ) ,胸X线片均表现为斑片状局灶性浸润性阴影 ,单侧病变者 1 5例 ,双侧病变者 1 8例。肺部病灶变化快 ,随病程进展而加重 ,部分患儿由单侧发展为双侧 ;肺部阴影消退较慢 ,明显吸收好转平均需 2周时间。ALT升高者 3例 ,CK MB升高者 2例。给予隔离、通风、充分休息、加强营养、低流量吸氧、中药清热解毒、预防细菌感染、抗炎症因子等综合治疗。住院天数 (1 0 0± 3 8)d。全部病例临床治愈出院。结论　儿童SARS有其自身临床特点 ,经综合治疗可有效治愈     

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。     

Adolescent twin sisters with severe acute respiratory syndrome (SARS)

A novel coronavirus-associated communicable respiratory disease, severe acute respiratory syndrome (SARS), spread worldwide after an outbreak in Guangdong Province of the People's Republic of China in November 2002. Since late February 2003, there has been an epidemic in Hong Kong involving both adult and pediatric patients. The clinical course, intensive care, and outcome of adolescent twin sisters with SARS are described. Adolescents infected with SARS may develop severe illness as adults, and close monitoring for disease progression in terms of both clinical and radiologic deterioration is warranted.     

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。     

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。     

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.     

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.     

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.