Human coronavirus NL63 associated with lower respiratory tract symptoms in early life

Coronavirus NL63 has been identified as a new member of the coronavirus genus, but its role as a cause of respiratory disease needs to be established. We studied the first episode of lower respiratory tract symptoms in a cohort of healthy neonates. NL63 was identified in 6 (7%) of 82 cases and was as frequent as other coronaviruses (9%). NL63 was recovered at the onset of symptoms and was cleared within 3 weeks in half of the cases. Our data suggests that coronavirus NL63 causes lower respiratory tract symptoms and is acquired in early life.     

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??Abstract??Objective??To establish a real-time fluorescent quantitative PCR assay to detect the human coronavirus NL63 from nasopharyngeal samples of children with acute respiratory tract infections in Fuzhou. Methods??The specific primers and Tap-man probes were designed targeting the 1a gene. The aimed fragment of 1a gene was amplified with PCR and ligated into a PMD18-T Easy vector for standards. A total of 151 clinical specimens were subsequently tested after determination of the sensitivity and specificity of the established real-time PCR. Amplify and preliminarily analyse the N gene. Results??The specificity of this assay was excellent. The linear amplification of the assay ranged from 101 copies/μL to 1010 copies/μL. Two of 151 clinical specimens??1.3%?? were tested positive for HCoV-NL63. Conclusion??The real-time fluorescent quantitative PCR assay is successfully established to detect HCoV- NL63 .     

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.     

Clinical manifestations of human coronavirus NL63 infection in children in Taiwan

Human coronavirus NL63 (HCoV-NL63) is a global respiratory tract pathogen; however, the epidemiology of this virus in subtropical area is not well known. To evaluate the epidemics and disease spectrum of HCoV-NL63 infection in children in Taiwan, we prospectively screened children admitted to the hospital with respiratory tract infection from May 2004 to April 2005. Every enrolled child had a nasopharyngeal aspirate (NPA) sample taken. Quantitative RT-PCR was used to detect 1b gene of HCoV-NL63. A total of 539 NPAs were collected. Seven (1.3%) were positive for HCoV-NL63. All cases were boys younger than 3 years of age and most cases occurred in autumn. Co-infection with other pathogens was observed in three cases. The most common symptoms/signs of HCoV-NL63 infection were cough, fever, and inspiratory stridor. HCoV-NL63 was the most common pathogen (14.7%) in children with croup and was the cause of three cases of croup in October. The odds ratio of croup in children infected with HCoV-NL63 was 43.4 (95% CI 8.1∼233.1). In conclusion, HCoV-NL63 is an important respiratory tract pathogen as the main cause in children admitted to the hospital in Taiwan.     

Rhinovirus as the main co-circulating virus during the COVID-19 pandemic in children

ObjectiveChanges in the epidemiology of respiratory infections during the restrictions imposed as a response to the coronavirus disease 2019 (COVID-19) pandemic have been reported elsewhere. The present study's aim was to describe the prevalence of a large array of respiratory pathogens in symptomatic children and adolescents during the pandemic in Southern Brazil.MethodsHospitalized and outpatients aged 2 months to 18 years with signs and symptoms of acute COVID-19 were prospectively enrolled in the study from May to November 2020 in two hospitals in a large metropolitan area in a Brazilian city. All participants performed a real-time PCR panel assessing 20 respiratory pathogens (three bacteria and 17 viruses).Results436 participants were included, with 45 of these hospitalized. Rhinovirus was the most prevalent pathogen (216/436) followed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, 97/436), with a coinfection of these two viruses occurring in 31/436 participants. The remaining pathogens were found in 24 symptomatic participants (adenovirus, n = 6; Chlamydophila pneumoniae, n = 1; coronavirus NL63, n = 2; human enterovirus, n = 7; human metapneumovirus, n = 2; Mycoplasma pneumoniae, n = 6). Hospitalization was more common among infants (p = 0.004) and those with pathogens other than SARS-CoV-2 (p = 0.001).ConclusionDuring the period of social distancing in response to COVID-19, the prevalence of most respiratory pathogens was unusually low. Rhinovirus remained as the main virus co-circulating with SARS-CoV-2. COVID-19 in symptomatic children was less associated with hospitalization than with other respiratory infections in children and adolescents.     

Viral etiology of acute respiratory infections with cough in infancy: a community-based birth cohort study

BACKGROUND: Acute respiratory infections (ARI) are a major cause of morbidity in infancy worldwide, with cough and wheeze being alarming symptoms to parents. We aimed to analyze in detail the viral aetiology of ARI with such symptoms in otherwise healthy infants, including rhinoviruses and recently discovered viruses such as human metapneumovirus (HMPV), coronavirus NL63 and HKU1, and human bocavirus (HBoV). METHODS: We prospectively followed 197 unselected infants during their first year of life and assessed clinical symptoms by weekly standardized interviews. At the first ARI with cough or wheeze, we analyzed nasal swabs by sensitive individual real time polymerase chain reaction assays targeting 16 different respiratory viruses. RESULTS: All 112 infants who had an ARI had cough, and 39 (35%) had wheeze. One or more respiratory viruses were found in 88 of 112 (79%) cases. Fifteen (17%) dual and 3 (3%) triple infections were recorded. Rhino- (23% of all viruses) and coronaviruses (18%) were most common, followed by parainfluenza viruses (17%), respiratory syncytial virus (RSV) (16%), HMPV (13%), and HBoV (5%). Together rhinoviruses, coronaviruses, HMPV, and HBoV accounted for 60% (65 of 109) of viruses. Although symptom scores and need for general practitioner (GP) consultations were highest in infants infected with RSV, they were similar in infants infected with other viruses. Viral shedding at 3 weeks occurred in 20% of cases. CONCLUSIONS: Rhinoviruses, coronaviruses, HMPV, and HBoV are common pathogens associated with respiratory symptoms in otherwise healthy infants. They should be considered in the differential diagnosis of the aetiology of ARI in this age group.     

新发现呼吸道病毒感染的流行病学及其临床特征

呼吸道感染是儿科的常见病、多发病,是引起世界范围内5岁以下儿童死亡的首位原因.其临床表现易被认识,但病因却很难明确.2001年以来许多新的人类病毒被发现,其中人类偏肺病毒、人类冠状病毒NL63和HKU1,以及人类博卡病毒,均已被证实可引起小儿呼吸道疾病,其流行病学及临床特征也得到较为深入的研究.     

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。     

Frequency of asymptomatic and symptomatic respiratory virus detection in pediatric hematopoietic cell transplant patients

Respiratory viral infections are common and can cause significant morbidity and mortality in pediatric patients undergoing hematopoietic cell transplantation (HCT). The prevalence of disease has been primarily identified from retrospective studies using standard‐of‐care specimens. The incidence of both asymptomatic respiratory viral detection and symptomatic respiratory viral detection in this high‐risk population is not well described. We performed longitudinal, active, prospective surveillance in pediatric HCT patients. Subjects underwent weekly midturbinate swabs (MTSs) for the detection of 18 respiratory viruses and subtypes peri‐HCT and 100 days post‐HCT. Clinical data were obtained from the medical record. From September 2015 to February 2017, 24 children underwent 29 HCT, and 284 MTSs were collected. Forty‐two (15%) specimens were virus‐positive from 10 (42%) subjects. Specimens from children undergoing allogeneic HCT were more likely to have a virus detected (17% vs 8%, P = .04) compared with specimens from children undergoing autologous HCT. Sixteen (38%) detections were not associated with symptoms. Almost half (8/17) of the unique viral infections occurred during the HCT hospitalization after a negative specimen, suggesting nosocomial acquisition, and preceded detection from a clinical specimen. Rhinovirus, the most common virus detected, was the only virus detected in 33 (81%) virus‐positive specimens; only 11 (33%) rhinovirus detections were asymptomatic. Asymptomatic detection of coronavirus and bocavirus occurred. Asymptomatic respiratory virus detection occurred in more than one‐third of the children undergoing HCT. The acquisition of respiratory viruses during HCT hospitalization suggests nosocomial acquisition. Early detection of respiratory viruses during asymptomatic periods could have infection prevention and treatment implications.     

The cell biology of acute childhood respiratory disease: therapeutic implications

Respiratory syncytial virus (RSV), the recently identified human metapneumovirus (HMPV), and the human parainfluenza viruses (HPIVs), cause most cases of childhood croup, bronchiolitis, and pneumonia. Influenza virus also causes a significant burden of disease in young children, although its significance in children was not fully recognized until recently. This article discusses pathogens that have been studied for several decades, including RSV and HPIVs, and also explores the newly identified viral pathogens HMPV and human coronavirus NL63. The escalating rate of emergence of new infectious agents, fortunately meeting with equally rapid advancements in molecular methods of surveillance and pathogen discovery, means that new organisms will soon be added to the list. A section on therapies for bronchiolitis addresses the final common pathways that can result from infection with diverse pathogens, highlighting the mechanisms that may be amenable to therapeutic approaches. The article concludes with a discussion of the overarching impact of new diagnostic strategies.     

Human coronavirus OC43 pneumonia in a pediatric cancer patient with down syndrome and acute lymphoblastic leukemia

In this report, we describe a case of pneumonia due to an infection with human coronaviruses (HCoVs)-OC43 in a pediatric leukemia patient with Down syndrome and febrile neutropenia. Not only the recently discovered HCoVs NL63 or HKU1 but also the prototype strains HCoV-OC43 and HCoV-229E have to be considered as respiratory pathogens in immunocompromised pediatric cancer patients. The routine utilization of polymerase chain reaction-based diagnostic tools would certainly elucidate the etiology of a relevant proportion of "pneumonias of unknown origin" in immunocompromised pediatric patients and would contribute to a better understanding of the role of HCoVs in this setting.     

6岁以下儿童急性下呼吸道感染的病毒病原及临床研究

目的　了解北京地区 6岁以下儿童中急性下呼吸道感染 (ALRI)患儿的病毒感染状况 ;探讨人类偏肺病毒 (hMPV)感染在儿童ALRI中的作用及所致支气管肺炎的临床特征。方法　 (1)采集 2 0 0 1年 2月至 2 0 0 3年 3月就诊于首都儿科研究所 4 4 6例年龄 1个月至 5岁的ALRI住院患儿的鼻咽分泌物 ,同时应用间接免疫荧光 (IFA)及病毒分离方法进行人类呼吸道合胞病毒 (hRSV)、流感病毒 (甲、乙型 )、副流感病毒 (Ⅰ、Ⅱ、Ⅲ型 )及腺病毒等 7种常见呼吸道病毒的病原检测。 (2 )采用逆转录聚合酶链反应 (RT PCR)方法对 2 0 0 2年 11月至 2 0 0 3年 3月住我院内科的ALRI患儿中经 7种呼吸道常见病毒病原检测阴性的 2 16份鼻咽洗液 ,进行了hMPV基因检测 ,并分析hMPV感染患儿的临床资料。结果　 (1) 4 4 6例患儿中 7种常见呼吸道病毒总阳性例数为 2 0 9例 (46 86 % ) ,hRSV阳性者最多为 16 3例 (36 5 5 % )。 (2 )在 2 16份上述 7种呼吸道病原检测阴性的标本中 6 9份测到hMPV阳性扩增产物 (31 9% ) ,占同期送检标本的 19 17%。结论　 (1)hRSV是北京地区冬春季节婴幼儿ALRI的主要病原。 (2 )2 0 0 2年 11月至 2 0 0 3年 3月我院ALRI住院患儿中有 19 17%与hMPV感染有关     

Clinical role of respiratory virus infection in acute otitis media

The clinical characteristics of acute otitis media in relation to coexisting respiratory virus infection were studied in a 1-year prospective study of 363 children with acute otitis media. Respiratory viruses were detected using virus isolation and virus antigen detection in nasopharyngeal specimens of 42% of the patients at the time of diagnosis. Rhinovirus (24%) and respiratory syncytial virus (13%) were the two most common viruses detected. Adenovirus, parainfluenza viruses, and coronavirus OC43 were found less frequently. The mean duration of preceding symptoms was 5.9 days before the diagnosis of acute otitis media. Ninety-four percent of the children had symptoms of upper respiratory tract infection. Fever was reported in 55% and earache in 47% of cases. Patients with respiratory syncytial virus infection had fever, cough, and vomiting significantly more often than patients with rhinovirus infection or virus-negative patients. No significant differences were found in the appearance of the tympanic membrane and outcome of illness between virus-negative and virus-positive patients with acute otitis. Most patients respond well to antimicrobial therapy despite the coexisting viral infection. If the symptoms of infection persist, they can be due to the underlying viral infection, and viral diagnostics preferably with rapid methods may be clinically useful in these patients.     

Decreased lipid intake reduces morbidity in sick premature neonates

For an investigation of the clinical sequelae of parenteral lipid infusions during the first week of life, 42 neonates (less than 1750 gm birth weight) were randomly assigned to receive parenteral alimentation with (IL) (Vitrum) or without a parenteral lipid infusion (NL) for 5 days. Follow-up clinical status was monitored and compared, and plasma prostaglandin levels were analyzed. Chronic lung disease was increased in duration and tended to be more severe after lipid administration. The number of days of mechanical ventilation (37 +/- 35 vs 21 +/- 18) and supplemental oxygen therapy (51 +/- 39 vs 28 +/- 23) was significantly increased in the IL group. Five IL infants developed stage 3 bronchopulmonary dysplasia, in comparison with none of the NL infants. Seven IL infants were discharged on a regimen of supplemental oxygen therapy versus none of the NL infants. Thromboxane B2 levels were significantly increased in the babies receiving Vitrum. We conclude that early administration of Vitrum in the premature neonate is associated with increased respiratory difficulty in the ensuing weeks of life.     

从SARS、MERS到COVID-19看母婴垂直传播的可能性

评估孕妇感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）对新生儿2019冠状病毒病发病的潜在影响,探讨SARS-CoV-2母婴垂直传播的可能性。该文根据目前已经发表的相关文献和官方网站信息,分析总结了SARS、MERS期间及COVID-19暴发后报道的孕妇感染相关病毒后所分娩的新生儿病例的临床表现和实验室检查。从目前证据尚不足以得出COVID-19母婴垂直传播的结论,需累积更多的病例进一步评估。     

杭州市19例新型冠状病毒Omicron变异株感染儿童的临床特征

目的 探讨儿童新型冠状病毒Omicron变异株感染者的临床特征,为临床诊疗提供参考。方法 回顾性分析杭州市19例2022年1月28日至3月3日确诊为新型冠状病毒Omicron变异株感染儿童的临床资料。结果 19例患儿中,男性7例(37%),女性12例(63%);年龄0.5～16.0岁,中位年龄为2岁1个月,以婴幼儿(≤3岁)多见(53%)。未接种新型冠状病毒疫苗者11例(58%),接种者8例(42%)。3例(16%)有基础疾病史。19例患儿均有明确的新型冠状病毒感染者的密切接触史,其中母婴看护机构聚集性发病10例(53%)。临床表现为轻型13例(68%),普通型6例(32%),无重型病例。最常见症状为咳嗽(100%)和发热(63%)。患儿外周血白细胞计数(84%)及淋巴细胞计数多正常(68%)。患儿的血小板计数、降钙素原、肝功能指标(丙氨酸氨基转移酶、天冬氨酸氨基转移酶)、肾功能指标(肌酐、尿素)无明显异常。6例(32%)胸部CT有明显肺炎征象。19例患儿均给予对症治疗,12例(63%)雾化吸入干扰素α。所有患儿治愈出院。结论 儿童Omicron变异株感染病例以婴幼儿多见,症状轻,预后...     

从SARS、MERS到COVID-19看母婴垂直传播的可能性

评估孕妇感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）对新生儿2019冠状病毒病发病的潜在影响,探讨SARS-CoV-2母婴垂直传播的可能性。该文根据目前已经发表的相关文献和官方网站信息,分析总结了SARS、MERS期间及COVID-19暴发后报道的孕妇感染相关病毒后所分娩的新生儿病例的临床表现和实验室检查。从目前证据尚不足以得出COVID-19母婴垂直传播的结论,需累积更多的病例进一步评估。     

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??Abstract??Objective??To investigate the characteristics of adenovirus infection in children with acute respiratory tract infection. Methods??From May to June 2009?? 492 out-patients with acute respiratory tract infection were involved in our study. One throat swab specimen was collected from each patient. ??RT?? PCRs were performed to detect common respiratory tract viruses including respiratory syncytial virus ??RSV???? rhinovirus ??RV???? influzenza virus type A and B ??IFA?? IFB???? parainfluenza virus ??PIV?? type 1??4?? adenovirus ??AdV???? enterovirus ??EV???? human coronavirus ??HCoV???? human metapneumonia virus ??hMPV?? and human bocavirus ??HBoV??. AdV amplicons were cloned and sequenced to determine the AdV serotypes by using Blast and phylogenetic analysis. Results??At least one viral pathogen was detected in 165 out of 492 patients and the overall positive rate was 33.5%. AdV was detected in 53 ??10.8%?? specimens and it was the most common viral pathogen. Of the 53 AdV postive samples?? 3 subgroups and 7 serotypes were found. AdV serotype 3 ??23/53?? was the major serotype?? followed by serotype 7 ??8/53?? and serotype 1 ??7/53??. Conclusion??There were several AdV serotypes circulating in the spring of 2009 in Beijing area and serotype 3 was the predominant strain. AdV still playes an important role in acute respiratory tract infection in children.