Rhinovirus Infection In Children Research Articles

Evaluation of Clinical and Laboratory Features of Rhinovirus Infections in Children

Abstract Objective Our aim in this study was to evaluate the clinical characteristics of patients afflicted with rhinovirus (RV) infections, compare their laboratory findings with a healthy population, determine the features of the clinical course of the illness in individuals with a chronic disease, and set out the risk factors involved in the need for mechanical ventilation (MV). Methods The study was conducted on 318 pediatric patients aged 0 to 18 years diagnosed with RV infection. Patients were divided into two main groups, those with and without a chronic disease. The group with chronic disease was divided into four subgroups. Children with RV were compared with a control group of 231 healthy children. Results The most common symptoms and signs were wheeze (65.4%), cough (65.1%), and tachypnea (50.3%). Compared with the healthy population, RV-positive patients showed significant increases in their white blood cell (WBC), neutrophil, and platelet counts, and in their delta neutrophil index and C-reactive protein values (all p < 0.001). The most important risk factors in terms of the need for MV were elevated WBC (odds ratio [OR] = 1.404, 95% confidence interval [CI]: 1.059–1.862), chronic lung disease (CLD) (OR = 5.196, 95% CI: 2.296–11.762), reticular involvement (OR = 3.132, 95% CI: 1.259–7.793), and lobar involvement (OR = 10.575, 95% CI: 13.434–32.564). Conclusion It is of vital importance that individuals with asthma and CLD are closely monitored and protected during RV seasonal periods as they are most at risk of severe infection, which can require high-flow nasal cannula and MV.

Clinical and immunological features of the combined course of pertussis and rhinovirus infection in children

The association of pertussis with various respiratory infections in children is the leading factor determining the complicated course and unfavorable outcome of the disease.Objective. To analyze clinical and immunological features of the combined course of pertussis and rhinovirus infection.Children characteristics and research methods. The authors observed 20 patients: 10 (50%) children were under the age of 1 year, 5 (25%) children of 1–3 years old, 3 (15%) children of 4–6 years, 2 (10%) children of 7 -14 years old.Results. The rhinovirus infection developed mainly at 1-2 weeks of illness in 18 (90%) children. Bronchitis developed in 11 (55%) children, pneumonia – in 4 (20%). Special attention was drawn to the low content of NK cells in 82.4% of patients when assessing the subpopulation composition of lymphocytes. The cytokine profile was characterized by a low level of interferon-gamma and interferon-alpha production – in 94.4 and 61.1% of patients, respectively.Conclusion. The combination of pertussis and rhinovirus infection in children contributes to the uneven course of the disease, the frequent development of bronchopulmonary complications.

Clinical features of the course of Rhinoviral infection in children

Acute respiratory viral infections remain the most common diseases in the world, accounting for about 90% of all infectious diseases. The possibilities of etiological decoding of ARVI using modern examination methods made it possible to establish an increase in the proportion of rhinovirus infection in the structure of ARVI.The aim of the study in this regard was to study the features of the clinical course of rhinovirus infection in children of different ages in modern conditions. The study included 50 patients with rhinovirus infection of children, among whom 1 2 children (24%) were under 1 year old; 34 children (68%) — 1—3 years old, 4 children (8%) — 3—7 years old. To confirm rhinovirus infection, a study of mucus from the nasopharynx by PCR was carried out.A thorough analysis of the symptom complex of the infection showed that in 1 3 (26%) patients the infectious process was limited to lesions of the upper respiratory tract, in 14 (28%) there were symptoms of acute stenosinglaryngotracheitis, in 1 1 (22%) children developed pneumonia, in 1 2 (24%) — bronchitis, with obstructive syndrome in 1 0 (83.3%) patients in this group.

Increased risk of rhinovirus infection in children during the coronavirus disease-19 pandemic.

BackgroundCoronavirus disease (COVID‐19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), was first detected in Japan in January 2020 and has spread throughout the country. Previous studies have reported that viral interference among influenza virus, rhinovirus, and other respiratory viruses can affect viral infections at the host and population level.MethodsTo investigate the impact of COVID‐19 on influenza and other respiratory virus infections, we analyzed clinical specimens collected from 2244 patients in Japan with respiratory diseases between January 2018 and September 2020.ResultsThe frequency of influenza and other respiratory viruses (coxsackievirus A and B; echovirus; enterovirus; human coronavirus 229E, HKU1, NL63, and OC43; human metapneumovirus; human parainfluenza virus 1, 2, 3, and 4; human parechovirus; human respiratory syncytial virus; human adenovirus; human bocavirus; human parvovirus B19; herpes simplex virus type 1; and varicella‐zoster virus) was appreciably reduced among all patients during the COVID‐19 pandemic except for that of rhinovirus in children younger than 10 years, which was appreciably increased. COVID‐19 has not spread among this age group, suggesting an increased risk of rhinovirus infection in children.ConclusionsRhinovirus infections should be continuously monitored to understand their increased risk during the COVID‐19 pandemic and viral interference with SARS‐CoV‐2.

Rhinovirus Infection in Children—a Narrative Review

First discovered in the 1950s, rhinoviruses (RVs) are linked to a broad spectrum of clinical syndromes, particularly in young children. RVs cause greater morbidity than previously recognized and impose substantial health care expenditure and missed days of work due to physician visits, hospitalization, and childcare. Our understanding of the genomic structure of RVs has increased with advances in molecular methods. RT-PCR is the most commonly used method for RV detection at present. Currently, treatment of RV infection is mostly supportive; there are no approved antiviral medications available yet. This review aims to provide the most current information on clinical syndromes, pathogenesis, host immunological responses, diagnostics, and therapeutic and preventive strategies related to RV infection in children.

Rhinovirus Infection in Children with Acute Bronchiolitis and Its Impact on Recurrent Wheezing and Asthma Development.

Acute bronchiolitis represents the leading cause of hospitalization in infants. Together with a respiratory syncytial virus, rhinovirus (RV) is one of the most common pathogens associated with bronchiolitis, and its genetic diversity (>150 types) makes the recurrence of RV infections each year quite typical. The frequency of RV infection and co-infection with other viruses and its impact on the clinical course of bronchiolitis have been studied by several authors with controversial results. Some studies demonstrate that multiple virus infections result in more severe clinical presentation and a higher risk of complications, whereas other studies suggest no influence on clinical course. Moreover, RV bronchiolitis has been reported to potentially contribute to the development of long-term sequelae, such as recurrent wheezing and asthma, in the pediatric population. In the present review, we summarize the most recent findings of the role of RV infection in children with acute bronchiolitis, its impact on subsequent asthma development, and the implication in clinical practice.

High incidence of rhinovirus infection in children with community-acquired pneumonia from a city in the Brazilian pre-Amazon region.

Community‐acquired pneumonia (CAP) is the leading cause of child death worldwide. Viruses are the most common pathogens associated with CAP in children, but their incidence varies greatly. This study investigated the presence of respiratory syncytial virus (RSV), adenovirus, human rhinovirus (HRV), human metapneumovirus (HMPV), human coronavirus (HCoV‐OC43 and HCoV‐NL63), and influenza A virus (FluA) in children with CAP and the contributing risk factors. Here, children with acute respiratory infections were screened by pediatrics; and a total of 150 radiographically‐confirmed CAP patients (aged 3 months to 10 years) from two clinical centers in Sao Luis, Brazil were recruited. Patient's clinical and epidemiological data were recorded. Nasopharyngeal swab and tracheal aspirate samples were collected to extract viral nucleic acid. RSV, adenovirus, rhinovirus, FluA, HMPV, HCoV‐OC43, and HCoV‐NL63 were detected by real‐time polymerase chain reaction. The severe CAP was associated with ages between 3 and 12 months. Viruses were detected in 43% of CAP patients. Rhinovirus infections were the most frequently identified (68%). RSV, adenovirus, FluA, and coinfections were identified in 14%, 14%, 5%, and 15% of children with viral infection, respectively. Rhinovirus was associated with nonsevere CAP (P = .014); RSV, FluA, and coinfections were associated with severe CAP (P < .05). New strategies for prevention and treatment of viral respiratory infections, mainly rhinovirus and RSV infections, are necessary.

Impact of Rhinovirus Infections in Children

Rhinovirus (RV) is an RNA virus that causes more than 50% of upper respiratory tract infections in humans worldwide. Together with Respiratory Syncytial Virus, RV is one of the leading causes of viral bronchiolitis in infants and the most common virus associated with wheezing in children aged between one and two years. Because of its tremendous genetic diversity (>150 serotypes), the recurrence of RV infections each year is quite typical. Furthermore, because of its broad clinical spectrum, the clinical variability as well as the pathogenesis of RV infection are nowadays the subjects of an in-depth examination and have been the subject of several studies in the literature. In fact, the virus is responsible for direct cell cytotoxicity in only a small way, and it is now clearer than ever that it may act indirectly by triggering the release of active mediators by structural and inflammatory airway cells, causing the onset and/or the acute exacerbation of asthmatic events in predisposed children. In the present review, we aim to summarize the RV infection’s epidemiology, pathogenetic hypotheses, and available treatment options as well as its correlation with respiratory morbidity and mortality in the pediatric population.

Progress in human rhinovirus infection in children

Human rhinovirus(hRV )has been recognized as an important pathogen causing respiratory tract infections in children.HRV belongs to the small RNA virus family.The viral capsid consists of four viral capsid proteins, VP1, VP2, VP3 and VP4.VP1 is the major antigen that producing protective antibodies.There are more than 120 serotypes of hRV.HRV is transmitted mainly through the respiratory tract, and infants are susceptible to hRV.HRV binds intercellular adhesion molecule -1(ICAM-1)of airway epithelial cells, replicating in airway epithelial cells and local lymph tissues, causing inflammatory reaction and releasing inflammatory mediators, which can cause respiratory symptoms.HRV can not only cause respiratory tract infection, but also has close relationship with the onset of asthma in children.Among the various detection methods, RT-PCR has been proved to be rapid and sensitive, and widely used in the detection of hRV.Anti-hRV drugs are still in development. Key words: Human rhinovirus; Children; Respiratory tract infection; Asthma

Epidemiological analysis and follow-up of human rhinovirus infection in children with asthma exacerbation.

To determine the prevalence of human rhinovirus (HRV) infection in children with acute asthma exacerbations, investigation of HRV viral load and severity of asthma exacerbations is also required. Nasopharyngeal aspirates and swabs were collected and assessed for respiratory viruses. HRV‐positive samples were sequenced to identify types and determine viral load. Outpatients with asthma exacerbations underwent follow‐up evaluations, their swabs were collected and clinical outcomes were recorded at their next clinic visit 4 weeks later. One hundred forty‐three inpatients and 131 outpatients, including 88 patients with asthma exacerbations and 43 controls with stable asthma were recruited. HRV‐A was mainly detected in September and February (45.5% and 33.3%, respectively), while HRV‐C was mainly detected in November and April (70.0% and 55.6%, respectively). HRV‐C was the primary type and was primarily found in inpatients with severe asthma exacerbations. HRV‐A viral load in the group of inpatients with severe exacerbations was higher than in the mild and moderate groups (P < 0.001 and P = 0.022). The HRV‐A viral load of both inpatients and outpatients was higher than that of HRV‐C (P < 0.001 and P = 0.036). The main genotypes were HRV‐C53 and HRV‐A20 among inpatients, and this genotype caused more severe clinical manifestations. HRV persisted for no more than 4 weeks, and their symptoms or signs of disease were well‐controlled well. HRV‐C was most frequently detected in asthma exacerbations. HRV‐A with high viral load led to severe asthma exacerbations.

Frequency and Duration of Rhinovirus Infections in Children With Cystic Fibrosis and Healthy Controls: A Longitudinal Cohort Study.

Respiratory viral infections are an important cause of morbidity in patients with chronic respiratory diseases, such as cystic fibrosis (CF). We hypothesized that patients with CF are more susceptible to human rhinovirus (HRV) infections than healthy controls. In a 6-month winter period, 20 young children with CF (0-7 years) and 18 age-matched healthy controls were sampled biweekly for HRV-polymerase chain reaction using nasopharyngeal swabs, irrespective of respiratory symptoms. Respiratory symptoms were scored twice a week. If any symptom was present, an additional sample was obtained. All HRV-positive samples were genotyped to distinguish HRV subtypes. We analyzed 645 samples, with comparable total numbers of samples in both groups. HRV was detected in 40.8% of all analyzed samples. Children with CF had significantly more HRV-positive samples compared with healthy controls, with a mean number (± standard deviation) of 8.1 ± 2.3 versus 5.7 ± 2.9 positive samples per individual (P < 0.01). Prolonged detection (>2 weeks) with the same HRV subtype occurred more frequently in the CF patients (P < 0.01). The genetic distribution and pattern of phylogenetic diversity of the different HRV subtypes were similar in both groups. This is the first in vivo longitudinal study showing that HRV is detected more frequently and persists for longer periods in CF patients compared with healthy controls. This might indicate increased viral replication and/or decreased antiviral defense in patients with CF.

Seasonal variations of respiratory viruses and etiology of human rhinovirus infection in children

BackgroundUsing the polymerase chain reaction (PCR) method it is possible to detect uncultivable viruses and discover multiple viral infections. However, the clinical importance of these findings in relation to symptoms is not known. ObjectivesThe seasonal fluctuations of respiratory viruses and the clinical outcomes of single infections and dual infections were investigated. Study designNasal aspirate samples were obtained from outpatients and inpatients of a children’s hospital and these samples were subjected to real-time PCR to detect 16 respiratory viruses. Seasonal variations of the 16 viruses and the clinical outcomes such as wheezing, the need for oxygenation and prolonged hospitalization of patients with single viral infections and multiple infections were determined for the 5 most often detected viruses. ResultsAmong 512 specimens analyzed, one or more viruses were detected in 424 (83%) specimens. Two or more viruses were detected in 160 samples (31% of all samples). The epidemic peaks of the viruses did not coincide with each other. Rhinoviruses were the most frequently detected viruses and their coinfection rates were also higher. However, the disease severity in the lower respiratory tract did not differ in most respiratory viral infections regardless of whether there was single infection or dual infection with a rhinovirus and other respiratory virus. ConclusionsSeasonal distribution was seen for each virus. There were no significant differences in clinical symptoms in the children studied. Because the infection of rhinoviruses is the common occurrence in children, it is hypothesized that the factors related to disease severity are mainly the underlying conditions of the children.

Human rhinovirus infection in children with acute lower respiratory tract infections

Objective To investigate the clinical and molecular epidemiologic features of human rhinovirus (HRV) in children with acute lower respiratory tract infection (ALRTI) in Shanghai by detecting HRV from bronchoalveolar lavage fluid (BALF). Methods One hundred and thirty-five BALF samples were collected from children with ALRTI at Children's Hospital of Fudan University from January to June in 2014. The specimens were tested by one-step real-time reversible transcription (RT)-polymerase chain reaction (PCR) for HRV. Gene fragments of VP4/VP2 capsid protein of the HRV genome were amplified and sequenced. The phylogenetic trees of HRV strains were drawn. Chi-square test was used for statistical analysis. Result Among these 135 samples, 6(4.4%) were HRV positive, including 4 positive for HRV-A and 2 positive for unknown genotype. The age of children with HRV positive was 8 months to 8 years, including 5 cases ≤3 years old. The nucleotide homology within 4 HRV-A samples varied 76.5%-100.0%. These 4 HRV-A sequences were respectively compared with reference strains of HRV-A, HRV-B and HRV-C in GenBank. The nucleotide homology varied 73.1%-91.7%, 57.8%-66.0% and 59.0%-65.0%, respectively. Among 135 children with ALRTI, 124 were diagnosed with ordinary pneumonia including 4 (3.2%, 4/124) HRV positive and 11 were diagnosed with severe pneumonia (with respiratory failure and/or heart failure) including 2 HRV positive. All children with HRV presented with fever and cough. Most of them (5/6) were co-infected with other pathogens. In 5 children with HRV positive, the peripheral blood leukocyte counts were less than 10×109/L, neutrophil percentages were less than 0.50, C-reactive protein was less than 8 mg/L and procalcitonin was less than 0.05 μg/L. All the children were clinically cured. Conclusions The detection of HRV in BALF samples indicates that HRV is one of the pathogens in children with ALRTI in Shanghai and HRV-A is more common. Gene fragments of VP4/VP2 capsid protein of HRV pathogenic strains display a high degree of genetic variability. Key words: Rhinovirus; Child; Acute lower respirtory infections; Bronchoalveolar lavage fluid

Clinical relevance of rhinovirus infections in children at the critical care unit

Clinical relevance of rhinovirus infections in children at the critical care unit

Molecular epidemiology of rhinoviruses in Cyprus over three consecutive seasons.

Human rhinoviruses (HRVs) are widespread respiratory pathogens and a major cause of acute respiratory tract infections. The aim of this study was to investigate the molecular epidemiology of rhinovirus infections in children in Cyprus over three consecutive winter seasons. From a total of 116 rhinovirus-positive samples, 68 were sequenced in the 5'-UTR and VP4/VP2 regions. Thirty-six (52.9%) samples were identified as HRV-A and 27 (39.7%) as HRV-C, with only five (7.4%) samples belonging to the HRV-B species. Of these, a total of 46 different genotypes were identified. In the VP2/VP4 phylogenetic tree all strains clustered in three different well-defined clades, whereas the 5'-UTR tree exhibited clades with a mixed clustering of HRV-A and HRV-C strains reflecting the evolutionary history of recombination between HRV-A and HRV-C that has been observed previously. In summary, a high intra- and inter-season diversity of HRV types was observed. Despite its geographical isolation the frequency of HRV species in Cyprus is comparable to that reported in other regions of the world supporting the concept of an unrestricted global circulation. This study assesses, for the first time, the epidemiology of rhinovirus infections in Cypriot children and will be helpful to clinicians and researchers interested in the treatment and control of viral respiratory tract infections.

Human Rhinovirus Infection in Children with Cystic Fibrosis

Nasopharyngeal swabs obtained from 78 pediatric patients with cystic fibrosis (CF), including 47 with acute pulmonary exacerbation and 31 in a stable clinical condition, were evaluated for 17 respiratory viruses. Human rhinovirus (HRV) was the most frequently detected virus in patients with pulmonary exacerbation and in those who were clinically stable (21.3% vs. 12.9%; P = 0.52). HRV-A was the main RV detected in patients with pulmonary exacerbations. However, no prevalence of particular HRV-A subtypes was found. This study highlights that RV is frequently found in the respiratory secretions of patients with CF and the impact of HRV-A appears higher than that of the other HRV types in patients with pulmonary exacerbations.

Patient characteristics and severity of human rhinovirus infections in children

BackgroundIt is increasingly recognized that human rhinoviruses (HRV) can be associated with severe infections. However, conflicting results have been reported on the relative prevalence and severity of the three HRV species. ObjectivesThe relative prevalence and clinical characteristics of HRV-A, B and C, in children attending a South London teaching hospital were investigated retrospectively. Study designChildren aged <16 years with episodes of respiratory tract infections and detectable entero/rhinovirus RNA in respiratory samples between November 2009 and December 2010 were investigated. Retrospective case review was performed and patients’ characteristics recorded. ResultsEntero/rhinoviruses were the commonest viral pathogens (498/2316; 21.5%). Amongst 204 infection episodes associated with entero/rhinovirus, 167 were typed HRV, HRV-C was the most prevalent (99/167, 59.3%) followed by HRV-A (60/167; 35.9%) and HRV-B (8/167, 4.8%). The severity spectrum of HRV-A and HRV-C infections were similar and affected all parts of the respiratory tract. Co-pathogens were observed in 54 (26.5%) episodes. Severity was increased in patients with non-viral co-pathogens and those with an underlying respiratory condition. Univariate and multiple regression analyses of potential prognostic variables including age, co-pathogens and underlying respiratory illnesses showed that mono-infection with HRV-C, as compared with other HRV species, was associated with more severe disease in young children <3 years. ConclusionsHRV-C was the most prevalent species and on its own was associated with severe disease in children <3 years. The association between infection with HRV species and clinical presentation is complex and affected by many confounding factors.

Virus shedding after human rhinovirus infection in children, adults and patients with hypogammaglobulinaemia

The shedding of human rhinovirus (HRV) after an acute, naturally acquired infection has not been described in detail. We determined the duration of HRV shedding in immunocompetent children and adults, and in patients with primary hypogammaglobulinaemia. Subjects with symptoms of respiratory tract infection, and their household contacts, were screened for HRV by reverse transcription PCR. They were followed by serial, self-collected nasal swab specimens until negative for HRV or infected by another HRV type. We followed 62 HRV infections in 54 subjects. The mean (95% CI) duration of HRV shedding was 11.4 (8.2–14.7) days in children, 10.1 (7.4–12.9) days in adults, and 40.9 (26.4–55.4) days in patients with hypogammaglobulinaemia (p <0.001). The duration of respiratory tract symptoms correlated with the duration of virus shedding (p 0.002). A new infection by another HRV type soon after the first episode was common. We conclude that the shedding times of HRV are relatively short in otherwise healthy individuals. In contrast, prolonged shedding over 28 days is frequent in patients with hypogammaglobulinaemia despite immunoglobulin replacement therapy.

Deficient antiviral immune responses in childhood: Distinct roles of atopy and asthma

Impaired immune response to viral infections in atopic asthmatic patients has been recently reported and debated. Whether this condition is present in childhood and whether it is affected by atopy per se deserves further investigation. We sought to investigate airway interferon production in response to rhinovirus infection in children who are asthmatic, atopic, or both and its correlation with the airway inflammatory profile. Bronchial biopsy specimens and epithelial cells were obtained from 47 children (mean age, 5 ± 0.5 years) undergoing bronchoscopy. The study population included asthmatic children who were either atopic or nonatopic, atopic children without asthma, and children without atopy or asthma. Rhinovirus type 16 induction of IFN-λ and IFN-β mRNA and protein levels was assessed in bronchial epithelial cell cultures. The immunoinflammatory profile was evaluated by means of immunohistochemistry in bronchial biopsy specimens. Rhinovirus type 16-induced interferon production was significantly reduced in atopic asthmatic, nonatopic asthmatic, and atopic nonasthmatic children compared with that seen in nonatopic nonasthmatic children (all P< .05). Increased rhinovirus viral RNA levels paralleled this deficient interferon induction. Additionally, IFN-λ and IFN-β induction correlatedinversely with the airway T(H)2 immunopathologic profile (eosinophilia and IL-4 positivity: P< .05 and r= -0.38 and P< .05 and r= -0.58, respectively) and with epithelial damage (P< .05 and r= -0.55). Furthermore, total serum IgE levels correlated negatively with rhinovirus-induced IFN-λ mRNA levels (P< .05 and r= -0.41) and positively with rhinovirus viral RNA levels (P< .05 and r= 0.44). Deficient interferon responses to rhinovirus infection are present in childhood in asthmatic subjects irrespective of their atopic status and in atopic patients without asthma. These findings suggest that deficient immune responses to viral infections are not limited to patients with atopic asthma but are present in those with other T(H)2-oriented conditions.

Human rhinovirus infection in children with lower respiratory tract infection and asthmatic children in southern Taiwan

Human rhinovirus infection in children with lower respiratory tract infection and asthmatic children in southern Taiwan