A Single Center Observational Study on Clinical Manifestations and Associated Factors of Pediatric Long COVID.

Children with SARS-CoV-2 are mostly mild symptomatic, but they may develop conditions, such as persisting symptoms, that may put them at greater risk of complications. Our aim was to evaluate the frequency and the presence of risk factors for persisting COVID-19 symptoms in children. We carried out a prospective observational study of the clinical manifestation of Long COVID at the Department of Maternal Infantile Science of a tertiary University hospital in Rome. We included 697 children (0-18 years), with previous SARS-CoV-2 infection. Children and parents were asked questions regarding persistent symptoms of COVID-19. Children with symptoms 30 days after initial diagnosis were 185/697 (26.4%). Moreover, 81/697 (11.6%) patients presented symptoms 90 days after the diagnosis. Thirty-day-persisting symptoms were mostly present in children with anosmia, atopy, asthenia, and cough in the acute phase compared with the asymptomatic children 30 days after infection. After 90 days, symptoms described were mainly neurological (47/697 children, 6.7%), and headache (19/697; 2.7%) was the most frequent manifestation. In conclusion, a relatively large proportion of the patients reported persisting symptoms that seem to be related to the symptom burden and to the atopy. Ninety days after the infection, most of the children had recovered, showing that long-term effects are not frequent. Limitations of the study include the single-center design and the lack of a control group.

HMGB1 in Pediatric COVID-19 Infection and MIS-C: A Pilot Study.

Objective: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, a novel syndrome known as a multisystem inflammatory syndrome in children (MIS-C) was reported in previously healthy children. A possible pro-inflammatory molecule, high-mobility group box 1 (HMGB1), may be assumed to play an important role in the pathogenesis and clinical presentation of MIS-C. We described the clinical picture of patients with MIS-C and we also aimed to test and compare HMGB1 serum levels of MIS-C patients with those of patients with previous SARS-CoV2 infection and healthy children. Study design: We determined HMGB1 levels by Western blot in 46 patients and divided them into three groups, namely, five patients with MIS-C (median age: 8.36 years), 20 children with a history of SARS-CoV-2 infection (median age: 10.45 years), and 21 healthy children (controls) (median age: 4.84 years), without evidence of respiratory infection in the last 3 months. Results: The median level of HMGB1 in the serum of five patients with MIS-C was found to be significantly higher compared with both patients with a recent history of COVID-19 (1,151.38 vs. 545.90 densitometric units (DU), p = 0.001) and control (1,151.38 vs. 320.33 DU, p = 0.001) groups. The HMGB1 level in MIS-C patients with coronary involvement had a slightly higher value with respect to patients without coronary dilatation (1,225.36 vs. 1,030.49 DU, p = 0.248). In two of the five children with MIS-C that performed a follow-up, the HMGB1 value decreased to levels that were superimposable to the ones of the control group. Conclusion: The significantly high level of HMGB1 protein found in the serum of COVID-19 and patients with MIS-C supports its involvement in inflammatory manifestations, suggesting HMGB1 as a potential biomarker and therapeutic target in patients with severe illness.

Low lymphocyte count: A clinical severity marker in infants with bronchiolitis.

BACKGROUND: Bronchiolitis is the most frequent cause of hospitalization in infants younger than 1 year of age. We sought to evaluate the correlation between lymphocyte count and clinical manifestation in infants hospitalized with bronchiolitis. MATERIALS AND METHODS: We performed a retrospective cohort study evaluating 1297 children hospitalized for bronchiolitis from 2004 to 2019. A nasal washing was tested for 14 respiratory viruses by PCR. A clinical severity score, ranging 0-8, was assigned at hospital admission. History and clinical course were recorded for each infant. Patients were divided in 3 groups according to lymphocyte count tertiles. Parents of enrolled patients have been phoned annually over 5 years to evaluate respiratory sequelae. RESULTS: A total of 433 children had 2914.2 ± 745.5/mm3 lymphocytes (Group 1), 432 had 4897.6 ± 561.5/mm3 lymphocytes (Group 2) and 432 had 7884 ± 1903.3/mm3 lymphocytes (Group 3). Group 1 patients were more frequently infected by RSV and presented with fever, a worse clinical severity score. They more frequently needed oxygen supplementation, underwent a prolonged hospitalization needed to be admitted to pediatric intensive care unit. Finally, they had more frequently a family history of eczema, wheezing and asthma. We found no differences between lymphocytes count and respiratory sequelae (at least two episodes of wheezing per year). CONCLUSIONS: Infants with low lymphocyte count are more likely to have a worse clinical course of bronchiolitis.

Lung function at school age in infants with lower respiratory tract infections with and without wheezing: A birth cohort study.

OBJECTIVE: To evaluate the relationship between lower respiratory tract infections (LRTI), in the first 2 years of life and lung function at school age in the Piccolipiù birth cohort (Italy). METHODS: Data on LRTI (doctor diagnosis of bronchitis, bronchiolitis, pneumonia) and wheezing (≥3 episodes or a diagnosis of asthmatic bronchitis) in the first 2 years of life were obtained from parental questionnaires. Lung function was assessed at 7 years by spirometry and forced volume vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, forced expiratory flow between 25% and 75%, and at 75% of FVC (FEF25-75 and FEF75 ) were reported as Z-scores. The associations between LRTI and spirometric variables were estimated with linear regression models. RESULTS: Among 877 children studied, 22.1% had LRTI only, 5.4% wheezing only, 13.2% had both, and 59.3% had neither LRTI nor wheezing. Children with LRTI had lower FVC and FEV1 than children without (Z-score differences: -0.18 [95% confidence intervals: -0.31; -0.06] and -0.15 [-0.27; -0.03]). When children were stratified by history of both LRTI and wheezing, there was no association between LRTI only and spirometric values. Conversely, having had both LRTI and wheezing was inversely associated with all lung function measures: Z-score differences of -0.24 (-0.42; -0.07); -0.42 (-0.59; -0.24); -0.25 (-0.41; -0.08); -0.37 (-0.54; -0.21); -0.30 (-0.46; -0.14) for FVC, FEV1, FEV1 /FVC, FEF25-75 and FEF75, respectively. CONCLUSION: Infants with wheezing and LRTI, but not those with LRTI only, had reduced lung function at school-age.

Bronchiolitis phenotypes identified by latent class analysis may influence the occurrence of respiratory sequelae.

BACKGROUND: The heterogeneity of bronchiolitis may imply or reflect a different predisposition to respiratory sequelae. OBJECTIVE: Our aim was to investigate whether, among infants hospitalized with bronchiolitis, different clinical profiles extracted by latent class analysis (LCA) are associated with different risks of wheezing. METHODS: Over 15 consecutive epidemic seasons (2004-2019), we prospectively enrolled infants <1 year hospitalized for the first episode of bronchiolitis in a single tertiary hospital. A detailed clinical questionnaire was filled for each infant. LCA was applied to differentiate bronchiolitis phenotypes, and after hospital discharge, a phone interview was performed annually to record the presence of wheezing episodes. Adjusted multivariate regression analyses were run to investigate the risk of wheezing during 7 years follow-up according to clinical phenotypes. RESULTS: LCA performed on 1312 infants resulted in a three-class model. Profile 1 (65.5%): moderate bronchiolitis; Profile 2 (6.1%): severe bronchiolitis; and Profile 3(28.4%): bronchiolitis infants with high eosinophils blood count. At 1 year of follow up, about 50% of children presented wheezing in each profile. Compared to Profile 1, the adjusted odds ratio (OR) of having wheezing episodes was significantly higher in Profile 2 at 2, 3, and 4 years of follow-up. At 7 years, Profile 3 had an adjusted OR = 2.58, higher than Profile 2 (adjusted OR = 2.29). CONCLUSIONS: LCA clearly identified a "moderate", "severe," and "high eosinophils blood count" bronchiolitis. During the first 4 years after bronchiolitis, the "severe" profile showed the higher risk of wheezing, but after 7 years this risk seems higher in the "high eosinophils blood count" group.

Modifiable environmental factors predispose term infants to bronchiolitis but bronchiolitis itself predisposes to respiratory sequelae.

INTRODUCTION: Viral bronchiolitis is a common lower respiratory tract infection in infants. Environmental and genetic factors can favor respiratory tract infections. AIM: The aim of this study is to analyze risk factors for bronchiolitis and to investigate the predisposing factors for developing transient wheezing and asthma through a 6-year follow-up after hospitalization for bronchiolitis compared with a group of healthy controls that belonged to Piccolipiù cohort, who never had bronchiolitis. METHODS: We enrolled 645 infants hospitalized with bronchiolitis. A structured questionnaire was used to obtain demographic and clinical data. At 6 years of age, 370 cases and 183 controls were investigated for the presence of asthma by the structured questionnaire, for prick test and for spirometry, and were classified to asthmatic, transient wheezing, and no wheezing/no asthma. RESULTS: Breastfeeding was an independent protective factor (odds ratio [OR]: 0.3, 95% confidence interval [95% CI]: 0.2-0.4, p < 0.001) and tobacco smoke was a risk factor for the development of bronchiolitis (OR: 2.1, 95% CI: 1.4-3.1, p < 0.001). Analyzing follow-up, bronchiolitis increased the risk of developing transient wheezing by 12.9 (95% CI: 6.3-26.1, p < 0.001) and of developing asthma by 4.6 (95% CI: 1.9-10.7, p < 0.001). A positive family history of atopy increased the risk of developing asthma by 3.1 (95% CI: 1.4-6.7, p = 0.005). Asthmatic patients had a lower % FEV1, a lower % flow-volume curve (FVC), and a lower FEV1/FVC value, and they had more frequently positive skin prick test. CONCLUSION: Bronchiolitis is influenced by environmental factors: tobacco smoke increases its risk and breastfeeding is a protective factor. At the end of 6 years of follow-up, bronchiolitis is a significant risk factor to have pre-school wheezing and asthma.

Lung Ultrasound: Its Findings and New Applications in Neonatology and Pediatric Diseases.

Lung ultrasound has become increasingly used in both adult and pediatric populations, allowing the rapid evaluation of many lung and pleura diseases. This popularity is due to several advantages of the method such as the low cost, rapidity, lack of ionizing radiation, availability of bedside and repeatability of the method. These features are even more important after the outbreak of the SARS-CoV-2 pandemic, given the possibility of recognizing through ultrasound the signs of interstitial lung syndrome typical of pneumonia caused by the virus. The purpose of this paper is to review the available evidence of lung ultrasound (LUS) in children and its main applications in pediatric diseases.

Lung ultrasound compared to chest X-ray for the diagnosis of CAP in children.

BACKGROUND: Community-acquired pneumonia (CAP) represents one of the most common infectious diseases among children. Diagnosis of CAP is mainly clinical. Chest X-ray (CXR) remains the gold standard for the diagnosis in severe or controversial conditions. Recently, some authors have focused on the application of ultrasound in lung diseases but the role of lung ultrasound (LUS) in the diagnosis of CAP is still debated. We aimed to study the concordance between LUS and CXR in evaluating specific signs of CAP. As a secondary aim, we sought to determine the sensitivity and specificity of LUS in CAP diagnosis compared with CXR. Finally, we evaluated the role of LUS during the follow up. METHODS: We enrolled 68 children (<16 years old) hospitalized from October 2018 to September 2019 with a clinical and radiological diagnosis of CAP (cases: N = 41), or with no respiratory diseases (controls: N = 27), in whom a CXR was performed for clinical indications. All the children underwent LUS during hospitalization. The average time needed to perform LUS was 5-10 min for each child, and 19/41 cases were re-evaluated by LUS and CXR 30 days after discharge. RESULTS: Lung ultrasound confirmed CAP diagnosis in 40/41 patients. Concordance between the two techniques was K = 0.88 for the right lung and K = 0.70 for the left lung. Lung ultrasound showed a sensitivity of 97% and a specificity of 96% compared with CXR. At the follow up, sensitivity increased to 100% while specificity was 94%. CONCLUSIONS: Our study showed a potential benefit of LUS compared with CXR in the diagnosis and the follow up of CAP.

Is There a Chance of Normal Life in Severe Laryngeal web.

INTRODUCTION: Laryngeal web is a rare cause of pediatric stridor and respiratory distress. The clinical presentation is variable and symptoms usually correlate with the severity of the airway obstruction. CASE REPORTS: We describe the cases of three children unexpectedly diagnosed with laryngeal web after a severe episode of bronchiolitis and after thirteen and eleven years, respectively, of persistent symptoms despite asthma medications. CONCLUSION: Even if it is a rare cause of stridor and respiratory distress, congenital subglottic web could be a life threatening condition and clinicians should always consider it in the differential diagnosis of persistent noisy breathing, even in adolescents and young adults.

Lung ultrasound in bronchiolitis.

BACKGROUND: Bronchiolitis is the most common acute viral infection of the lower respiratory tract in infants. Clinical severity is associated with different risk factors; however, no clinical, laboratory, or radiological findings are able to predict the course of the disease in full-term infants. Lung ultrasound (LUS) is a valid technique for the diagnosis and evaluation of pediatric respiratory diseases. AIMS: The aim of our study was to correlate an LUS score with a clinical score, to describe lung ultrasound findings in cases and controls, and to compare LUS findings with chest X-ray (CXR) in infants hospitalized with bronchiolitis. METHODS: We conducted a single-center, longitudinal, prospective study on 92 infants. Sixty-three out of 92 infants were hospitalized for acute bronchiolitis (cases) and twenty-nine out of 92 for diseases not involving the respiratory system (controls). All patients with bronchiolitis underwent a clinical evaluation with the assignment of a clinical severity score and performed lung ultrasound with the assignment of an LUS score. Twenty-three out of 63 infants with bronchiolitis underwent also a CXR for clinical indications. Control infants performed only LUS. RESULTS: In infants with bronchiolitis LUS score showed a positive correlation with the clinical score (r = .62, p < .001) and the length of hospitalization (r = .42; p < .001). The need of oxygen therapy was more frequent in the patients with higher LUS score (p < .001). LUS findings observed in the cases were the presence of B-lines, subpleural consolidations, and abnormalities of the pleural line. No LUS alterations were observed in the controls. In patients who performed LUS and CXR, we found a correlation between the presence of abnormalities of the pleural line with LUS and the presence of air trapping with CXR (r = .55; p = .007).

A single centre study of viral community-acquired pneumonia in children: No evidence of SARS-CoV-2 from October 2019 to March 2020.

Pneumonia is an important cause of morbidity and mortality in children. We described viral aetiologies, with particular interest in detecting SARS-CoV-2, in hospitalized pneumonia children. Human rhinovirus was the most frequently detected agent. No children tested positive for SARS-CoV-2. Our findings suggest that SARS-CoV-2 infection is rare in children and it was not circulating in Rome before COVID-19 outbreak.

Age Limit in Bronchiolitis Diagnosis: 6 or 12 Months?

Aim: The most frequent cause of lower respiratory tract infection in infants is bronchiolitis. Up to now there is no agreement on the upper limit age of bronchiolitis. Our aim was to identify if there are clinical differences in infants hospitalized for bronchiolitis between 0-6 months and 6-12 months of age. A secondary aim was to establish whether there was differences in terms of recurrent wheezing at 12, 24, and 36 months of follow-up. Methods: We retrospectively analyzed clinical and virological records of 824 infants hospitalized for bronchiolitis during 11 consecutive epidemic seasons. From each infant at admission to the hospital nasopharyngeal washing was collected, clinical severity was assessed and clinical data were extracted from a structured questionnaire. At 12-24-36 months after discharge, parents were interviewed seeking information on recurrent wheezing. Results: A total of 773 infants (Group1) were ≤6 months of age, while 51 were >6 months (Group 2). No differences between family history for atopy and passive smoking exposure were observed between the two groups. Respiratory syncyzial virus was detected more frequently in Group 1 and human bocavirus in Group 2. The clinical severity score (p = 0.011) and the use of intravenous fluids (p = 0.0001) were higher in Group 1 with respect to Group 2 infants. At 36 months follow-up 163/106 (39.4%) Group 1 and 9/9 Group 2 infants experienced recurrent wheezing (p = 0.149). Conclusion: We demonstrated that 0-6 months old infants bronchiolitis differs from > 6 months bronchiolitis.

Nasal Microbiota in RSV Bronchiolitis.

Respiratory Syncytial Virus (RSV) is the leading cause of bronchiolitis, and the severity may be influenced by the bacterial ecosystem. Our aim was to analyze the nasal microbiota from 48 infants affected by bronchiolitis from RSV virus and 28 infants with bronchiolitis but negative for the virus. Results showed a significantly lower biodiversity in the RSV-positive group with respect to the RSV-negative group, a specific microbial profile associated with the RSV-positive group different from that observed in the negative group, and significant modifications in the relative abundance of taxa in the RSV-positive group, as well as in the RSV-A group, with respect to the negative group. Furthermore, microbial network analyses evidenced, in all studied groups, the presence of two predominant sub-networks characterized by peculiar inter- and intra-group correlation patterns as well as a general loss of connectivity among microbes in the RSV-positive group, particularly in the RSV-A group. Our results indicated that infants with more severe bronchiolitis disease, caused by RSV-A infection, present significant perturbations of both the nasal microbiota structure and the microbial relationships. Patients with a milder bronchiolitis course (RSV-B-infected and patients who have cleared the virus) presented less severe alterations.

Novel Variants of Respiratory Syncytial Virus A ON1 Associated With Increased Clinical Severity of Bronchiolitis.

BACKGROUND: A study of respiratory syncytial virus-A (RSV A) genotype ON1 genetic variability and clinical severity in infants hospitalized with bronchiolitis over 6 epidemic seasons (2012-2013 to 2017-2018) was carried out. METHODS: From prospectively enrolled term infants hospitalized for bronchiolitis, samples positive for RSV A ON1 (N = 139) were sequenced in the second half of the G gene. Patients' clinical data were obtained from medical files and each infant was assigned a clinical severity score. ANOVA comparison and adjusted multinomial logistic regression were used to evaluate clinical severity score and clinical parameters. RESULTS: The phylogenetic analysis of 54 strains showed 3 distinct clades; sequences in the last 2 seasons differed from previous seasons. The most divergent and numerous cluster of 2017-2018 strains was characterized by a novel pattern of amino acid changes, some in antigenic sites. Several amino acid changes altered predicted glycosylation sites, with acquisition of around 10 new O-glycosylation sites. Clinical severity of bronchiolitis increased in 2016-2017 and 2017-2018 and changed according to the epidemic seasons only. CONCLUSIONS: Amino acid changes in the hypervariable part of G protein may have altered functions and/or changed its immunogenicity, leading to an impact on disease severity.

Increased T-helper Cell 2 Response in Infants With Respiratory Syncytial Virus Bronchiolitis Hospitalized Outside Epidemic Peak.

AIM: To test the hypothesis that the balance of type-1/type-2 immune response differs between infants hospitalized with respiratory syncytial virus (RSV) bronchiolitis during the peak months and those during the nonpeak months. METHODS: We prospectively enrolled 90 unrelated full-term previously healthy infants hospitalized during the first year of life for RSV sole bronchiolitis over 2 epidemics (November 2016 to April 2017 and October 2017 to April 2018). We stratified infants as follows: hospitalized during the peak months (n: 71) and during the nonpeak months (n: 19). The frequencies of CD4+ producing interferon (IFN)-γ and interleukin (IL)-4 and of CD8+ producing IFN-γ T cells were measured by flow cytometry from infant peripheral whole blood. The T-helper cell (Th2) polarization index was calculated as the ratio between CD4+ T cells producing IL-4 and CD4+ T cells producing IFN-γ. RESULTS: Infants hospitalized during nonpeak months were significantly less frequently breast-fed, had a higher eosinophils count, a significantly higher percentage of CD4+ T cells producing IL-4 and higher Th2 polarization index than infants hospitalized during the peak months. CONCLUSIONS: We elucidated the presence of different endotypes in infants with RSV sole bronchiolitis. Previously healthy full-term infants hospitalized during the nonpeak months seem to be more likely those with a possible predisposition to atopy.

Differential interferon gene expression in bronchiolitis caused by respiratory syncytial virus-A genotype ON1.

Bronchiolitis severity is determined by a complex interaction among viral replication and antiviral immunity. The current respiratory syncytial virus (RSV)-A, genotype ON1 demonstrated a high replicative capacity but seemed to be clinically less severe than the previously circulating RSV-A, NA1. To learn insights about ON1 innate immune response, we analyzed expression levels of type I/III interferon (IFN)-related genes in the respiratory mucosa of infants with RSV bronchiolitis. We enrolled RSV-positive bronchiolitis patients over 12 epidemic seasons at a university hospital in Rome. From nasopharyngeal washings' cells (46 positive to NA1, 47 to ON1 and 28 to RSV-B, genotype BA), the mRNA copy number of the type III IFN receptor (IFNLR1 and IL10RB subunits), and of the type I/III IFN-stimulated genes, MxA and ISG56, was calculated using the threshold cycle relative quantification method with respect to an invariant gene. Expression levels of type III IFN receptor subunits genes positively correlated to each other and did not differ in infants infected with different RSV genotypes. The ISGs levels also positively correlated between them but differed among groups. MxA levels were significantly higher in NA1-infected infants than in those with ON1 and BA; ISG56 expression was slightly higher in NA1 than in the other strains. Interestingly, a moderate negative correlation existed between viral load and both ISGs values in ON1-infected infants only. The reduced ISG levels elicited during infections with ON1 (and BA) may cause a weaker control of RSV replication and/or an inadequate host immune response which may impact the risk of respiratory sequelae.

Human bocavirus in children hospitalized for acute respiratory tract infection in Rome.

BACKGROUND: The role of human bocavirus (HBoV) as a respiratory pathogen has not been fulfilled yet. We aimed to describe clinical and serological characteristics of children with HBoV hospitalized for acute respiratory tract infection and to evaluate whether differences occur between HBoV alone and in co-infection. METHODS: We retrospectively reviewed data from 60 children (median age of 6.2 months, range 0.6-70.9) hospitalized for acute respiratory symptoms, with HBoV detected from a respiratory sample, using a reverse transcriptase-PCR for 14 respiratory viruses (including respiratory syncytial virus (RSV), influenza virus A and B, human coronavirus OC43, 229E, NL-63 and HUK1, adenovirus, rhinovirus, parainfluenza virus1-3, and human metapneumovirus). RESULTS: HBoV was detected alone in 29 (48.3%) patients, while in co-infection with other viruses in 31 patients (51.7%), with a peak between December and January. Among the 60 patients, 34 were bronchiolitis, 19 wheezing, 3 pneumonia, 2 upper respiratory tract infection, and 2 whooping cough. Seven children (11.6%) required admission to the paediatric intensive care unit (PICU) for respiratory failure. No differences was observed in age, family history for atopy and/or asthma, clinical presentations, chest X-ray, or laboratory findings in children with HBoV alone vs. multiple viral detection. RSV was the most frequently co-detected virus (61.3%). When compared with HBoV detection alone, the co-detection of RSV and HBoV was associated with male sex (P = 0.013), younger age (P = 0.01), and lower blood neutrophil count (P = 0.032). CONCLUSIONS: HBoV can be detected alone and in co-infection respiratory samples of children with an acute respiratory tract infection. A cause-effect relationship between HBoV and respiratory infection is not clear, so further studies are needed to clarify this point.

Pertussis: New preventive strategies for an old disease.

In the last twenty years, despite high vaccination coverage, epidemics of pertussis are occurring in both developing and developed countries. Many reasons could explain the pertussis resurgence: the increasing awareness of the disease, the availability of new diagnostic tests with higher sensitivity, the emergence of new Bordetella pertussis (B. pertussis) strains different from those contained in the current vaccines, the asymptomatic transmission of B. pertussis in adolescents and adults and the shorter duration of protection given by the acellular pertussis (aP) vaccine. New preventive strategies have already been implemented, such as booster doses of aP vaccine in adolescents and adults, maternal immunisation during pregnancy and the "cocooning" strategy, but more are still needed. Knowing what is new about this old disease is necessary to reduce its incidence and to protect infants too young to be vaccinated, which have the highest risk of complications and death.

How Respiratory Syncytial Virus Genotypes Influence the Clinical Course in Infants Hospitalized for Bronchiolitis.

Background: We aimed to study respiratory syncytial virus (RSV) genotype distribution, clinical presentation, and disease severity in infants with bronchiolitis from RSV subtypes and new RSV genotypes. Methods: We prospectively enrolled previously healthy term infants less than 1 year old hospitalized for bronchiolitis in an Italian university hospital over 12 epidemic seasons. In 312 nasopharyngeal washings positive for RSV, we sequenced the viral genotype and analyzed this according to patient data. Strain-specific RSV loads were quantified for 273 specimens. Results: From 2005-2006 to 2011-2012, the RSV-A genotype NA1 predominated, and was replaced in 2012 by the novel ON1. All infants infected with RSV subtype B were genotype BA. Stratifying data according to genotypes NA1, ON1, and BA showed that NA1-infected infants were the youngest and had the most severe clinical course. Conversely, BA-infected infants had less severe symptoms and more frequently had eosinophilia and a family history of asthma. Infants with the ON1 genotype had a milder clinical course than those with NA1 and more risk factors for asthma, despite having the highest viral loads. Conclusion: The disease course in infants hospitalized for acute RSV bronchiolitis may depend on the RSV genotype.

Bronchiolitis clinics and medical treatment.

Bronchiolitis is the most common acute lower respiratory tract infection in infants and the first cause of hospitalization in this age group. Despite it has been studied for over 70 years, its management remains controversial and nowadays the treatment is only supportive. Pediatricians should be well acquainted with the clinical course of the disease. In particular, they should know that the severity of respiratory symptoms peaks between days 3-7 of the disease and dehydration is a key sign to consider for the management. In this review, we will discuss the most controversial points in the management of bronchiolitis according to six evidence-based guidelines, six clinical practice guidelines and five consensus-based reviews.