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.     

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.     

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.     

Detection of human bocavirus in hospitalised children

Aim:   The objectives of this study are to assess the frequency of human bocavirus (HBoV) infection in hospitalised children and to study the clinical symptoms associated with the detection of HBoV.
Methods:   Two groups of hospitalised children were included in this study: group 1 consisted of 1946 children hospitalised from 1st September 2004 to 30th May 2005, and group 2 consisted of 448 children hospitalised from 1st November 2003 to 30th March 2004. The respiratory specimens were tested by polymerase chain reaction.
Results:   In the first group, HBoV was detected by polymerise chain reaction in 11/828 (1.3%) of nasal specimens that tested negative for other respiratory viruses. One child tested positive for HBoV in both a nasal aspirate and stool sample. In the second group, nasal specimens were tested for all respiratory viruses, including HBoV. The presence of HBoV infection was detected in seven children (1.6%). Detection of a mixed viral population was observed in four of these children. The main symptoms in children infected with HBoV were rhinitis (50%), cough (45%), dyspnoea (28%), wheezing (28%), fever (23%) and diarrhoea (22%). The final clinical diagnoses were bronchiolitis (seven children), rhinopharyngitis (five children), the exacerbation of asthma (two children) and pneumonia (one child). Moreover, four children have associated gastroenteritis.
Conclusion:   These results contribute to the interest in the HBoV detection in children. HBoV detection in hospitalised children with or without any other respiratory virus detection was essentially associated with lower respiratory tract infection and in a lower score with upper respiratory tract infection and gastroenteritis.     

Outbreaks of human coronavirus in a paediatric and neonatal intensive care unit

Human coronavirus 229E (HCoV) has been recently recognized as a potential agent of nosocomial viral respiratory infections (NRVI) in high-risk infants. We have confirmed this as fact through the study of a 1-year period of HCoV outbreaks occurring during a prospective survey of NRVI in a paediatric and neonatal intensive care unit (PNICU) using new molecular techniques for HCoV detection. Nasal samples obtained at admission and weekly thereafter for all hospitalised children, as well as monthly nasal samples from staff, were analysed using immunofluorescence for respiratory syncitial virus (RSV), influenza viruses A and B, paramyxoviruses 1, 2, 3 and adenoviruses. RT-PCR was used for HCoV detection. During the year 1998, 43 HCoV-related NRVI were detected in 152 neonates (incidence 28.3%), and 7 HCoV-related NRVI were found in 92 children (incidence 7.6%). Three HCoV-related outbreaks were observed (February, August and December), associated with a high prevalence of HCoV infection in the staff. During the August outbreak, 50% to 78% of hospitalised neonates and children were infected. Seventy-five percent of hospitalised preterm neonates with a gestational age less than 32 weeks and 52.4% of staff members were infected. Risk factors for NRVI in neonates were birth weight, gestational age, ventilation, oxygenation and hospitalisation length. Ninety-two percent of infected preterm neonates were symptomatic, mainly with bradycardia and respiratory worsening. These data provide additional evidence for a possibly significant role of HCoV in NRVI in a PNICU. The role of staff or hospitalised children in spreading HCoV is hypothesised.     

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.     

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.     

Influenza-related hospitalisations in children

Aim:   To describe the disease burden, clinical pattern and outcome of influenza-related hospitalisations in children.
Methods:   This is a retrospective study carried out in a regional hospital in Hong Kong. Children hospitalised with established diagnosis of influenza infection from January to June of 2005 were studied. Length of hospitalisation, demographic characteristics, symptoms, clinical diagnosis and complications of influenza infection were analysed.
Results:   Influenza A infection accounted for 93.5% of these hospitalisations. Children less than 5 years of age comprised 70% of admission. Highest rate of admission occurred in May and April. One fourth of emergency admission during the study period and over 70% in the peak season was a result of influenza-related illness. Underlying medical disease was observed in 14.6% of children. Mean duration of hospitalisation was 3.0 days. Fever was the commonest presenting symptoms. Fever lasting for 7 days or more was observed in one-fifth of patients. Respiratory tract diseases (upper and lower) were the most frequent non-neurological diagnosis. Febrile convulsion was the complication observed in 27.6% of admission. One patient died as a result of acute necrotising encephalopathy.
Conclusion:   Influenza contributed to heavy health-care burden. Mortality was rare but did occur. Hospitalisations occurred in both healthy children and those with underlying chronic illness. Young children played an important role in such hospitalisations. Means to prevent influenza-associated morbidity and mortality especially among young children are needed.     

Risks of severity and readmission of Indigenous and non-Indigenous children hospitalised for bronchiolitis

Objective:   To describe the characteristics of children admitted to Royal Darwin Hospital with bronchiolitis, and to compare the severity of illness and incidence of subsequent readmission in Indigenous and non-Indigenous children.
Design, Setting and Participants:   Retrospective study of 101 children (aged ≤2 years) hospitalised with bronchiolitis to Royal Darwin Hospital between April 2005 and December 2006.
Main Outcome Measures:   Admission characteristics and indices of severity, treatment required (antibiotics etc.), reasons and incidence of readmissions (within 6 months).
Results:   Indigenous children had significantly more severe illness then non-Indigenous children ( n = 80 and 21, respectively), longer hospital stay (median = 6 and 3 days; P = 0.001) and oxygen requirement (median = 3 and 0; P = 0.004), pneumonia ( n = 14 and 0; P = 0.04) and antibiotics treatment (48 and 4; P = 0.001). The readmission rate for bronchiolitis was high (23%) with no significant difference between Indigenous and non-Indigenous children.
Conclusion:   Indigenous Australian children hospitalised with bronchiolitis have significantly more severe illness than non-Indigenous children. Points of intervention that can address this and the identified high readmission rate (within 6 months) are required.     

Respiratory syncytial virus infections in Central Australia

Background:   Little is known about the epidemiology of respiratory syncytial virus (RSV) infection in arid desert regions and in the Aboriginal population. We describe the seasonality and epidemiology of RSV infection in Central Australia, an arid area with a large Aboriginal population.
Methods:   Five-year retrospective study from 2000 through 2004 of children less than 2 years old admitted to Alice Springs Hospital with documented RSV infection.
Results:   RSV infection was documented in 173 children <2 years old admitted over a 5-year period, 165 community-acquired and 8 nosocomial. The annual incidence rate of community-acquired RSV infection in hospitalised Central Australian children <2 years old was 20.4 per 1000. The rate in Aboriginal children of 29.6 per 1000 children was significantly greater than in non-Aboriginal children of 10.9 per 1000 ( P < 0.0001). Associated risk factors were common; 52% of infected children had at least one other comorbidity. Younger children had more severe illness and longer duration of hospital stay. RSV-related illness peaked in winter but infections occurred throughout the year, and the winter predominance was less marked than in temperate climates.
Conclusions:   In the arid, desert region of Central Australia, RSV infection occurs throughout the year, but is more frequent in winter and more common in Aboriginal children. These data are important for understanding RSV epidemiology in desert regions, and for planning active or passive RSV immunoprophylaxis in these and other similar populations.     

Eleven consecutive years of respiratory syncytial virus outbreaks in Croatia

Background:  Respiratory syncytial virus (RSV) is the most common cause of severe lower respiratory tract infections (LRTI) in infants. The aim of the present study was to analyze the epidemiologic characteristics of RSV outbreaks in Croatian children.
Methods:  Over a period of 11 consecutive years (1994–2005), 3435 inpatients with acute respiratory infections (ARI) aged from birth to 10 years and were residing in Zagreb County were tested for infection with RSV and other respiratory viruses at the Virology Department, Croatian National Institute of Public Health. RSV was identified in nasopharyngeal secretions by isolation on cell culture and/or detection with monoclonal antibodies using a direct fluorescence assay.
Results:  RSV was the most common causative agent of ARI (42.2%; 658/1559) for the infants 0–6 months of age. It was also the etiologic agent of LRTI in 49% (495/1010) of infants of similar age. RSV was demonstrated in 56.5% (382/676) of infants with bronchiolitis, and in 36.5% (49/134) of those with pneumonia in this age group.
Conclusion:  The overall prevalence of RSV infection in Croatian children with acute respiratory illness, and its occurrence in various age groups, has remained stable over the past decade. RSV was found to be the most common cause of bronchiolitis occurring throughout childhood (52.7%; 482/913).     

Asthma and protracted bronchitis: Who fares better during an acute respiratory infection?

Aim:   Acute respiratory infections (ARI) are common in children, and symptoms range from days to weeks. The aim of this study was to determine if children with asthma have more severe ARI episodes compared with children with protracted bronchitis and controls.
Methods:   Parents prospectively scored their child's next ARI using the Canadian acute respiratory illness and flu scale (CARIFS) and a validated cough diary (on days 1–7, 10 and 14 of illness). Children were age- and season-matched.
Results:   On days 10 and 14 of illness, children with protracted bronchitis had significantly higher median CARIFS when compared with children with asthma and healthy controls. On day 14, the median CARIFS were: asthma = 4.1 (interquartile range (IQR) 4.0), protracted bronchitis = 19.6 (IQR 25.8) and controls = 4.1 (IQR 5.25). The median cough score was significantly different between groups on days 1, 7, 10 and 14 ( P  < 0.001). A significantly higher proportion of children with protracted bronchitis (63%) were still coughing at day 14 in comparison with children with asthma (24%) and healthy controls (26%).
Conclusion:   Children with protracted bronchitis had the most severe ARI symptoms and higher percentage of respiratory morbidity at day 14 in comparison with children with asthma and healthy controls.     

Coronavirus-associated pneumonia in previously healthy children

The extent to which coronaviruses are associated with lower respiratory tract disease in previously healthy children without underlying medical conditions is unknown. We investigated instances of radiographically confirmed lower respiratory tract disease among symptomatic children with coronavirus infection. Here, we document the clinical courses of 2 previously healthy children with coronavirus-associated pneumonia.     

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.     

Very high and increasing incidence of type 1 diabetes mellitus in Newfoundland and Labrador, Canada

Objective:  To determine the incidence of type 1 diabetes mellitus (T1DM) among children aged 0–14 yr inclusive in the Canadian province of Newfoundland and Labrador (NL).
Methods:  Prospective and retrospective cohort study of the incidence of T1DM in children aged 0–14 yr from 1987 to 2005. Identified cases during this time period were ascertained from several sources and verified using the capture–recapture technique.
Results:  Over the study period, 732 children aged 0–14 yr were diagnosed with T1DM. The incidence of T1DM in this population over the period 1987–2005 inclusive was 35.08 per 100 000 (95% confidence interval: 32.54, 37.62). The incidence over this period increased linearly at the rate of 0.78 per 100 000 per year. There was a significant difference between the incidence of 31.61 per 100 000 for boys in the 0–4-yr age-group and 19.05 per 100 000 for girls in the 0–4-yr age-group (p = 0.001). The incidence was very high throughout the entire province.
Conclusions/Interpretation:  The province of NL has one of the highest incidences of T1DM reported worldwide. The incidence is increasing over the 19-yr study period.     

���Ժ�������Ⱦ�����˹�״����NL63��������

??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 .     

Rhinovirus and acute respiratory infections in hospitalized children. Retrospective study 1998-2000]

OBJECTIVES: Rhinoviruses are the most common aetiological agents of colds, but the frequency and the severity of other locations of the infection are not well known. This study describes the clinical aspects and the severity of rhinovirus infections in hospitalised children. METHODS: Isolation in culture and a RT-PCR were performed for the detection of rhinovirus in nasal aspirates from hospitalised children from September 1998 to October 2000. A group of 211 children found to be positive for rhinovirus was studied. RESULTS: Rhinovirus-infected children suffered from the following clinical syndromes: 60 (28.4%) upper airway infections, 81 (38.4%) bronchiolitis, 25 (11.9%) pneumonias and 12 (4.7%) acute attacks of asthma. Clinical symptoms were wheezing (32%), ronchi (37%) and 29% of children presented with acute distress respiratory syndrome; 40% of the available chest X-Ray were abnormal. Eight children were hospitalised in the intensive care unit and two children died. Twenty-five children (10.9%) had a nosocomial infection; a dual infection was observed in 19 cases (9%) with the following viruses: RSV (3), influenza (2) parainfluenza (8), adenovirus (2), enterovirus (4); 19 (9%) children had a secondary bacterial infection. Rhinoviruses were detected in nasal aspirates in 112 cases (53%) according to the culture and in the rhinovirus culture-negative samples in 99 cases (47%) according to the RT-PCR assay. CONCLUSION: After eliminating cases of bacterial or viral dual infections, the clinical aspects of rhinovirus infections in children are the following: upper respiratory tract infections (25.6%), bronchiolitis ou bronchitis (25.6%), pneumonia (6.2%), acute attack of asthma (5.7%). The virological diagnosis according to culture is mainly improved by molecular techniques.