SARS-CoV-2-specific mucosal immune response in vaccinated versus infected children.

The anti-COVID-19 intramuscular vaccination induces a strong systemic but a weak mucosal immune response in adults. Little is known about the mucosal immune response in children infected or vaccinated against SARS-CoV-2. We found that 28% of children had detectable salivary IgA against SARS-CoV-2 even before vaccination, suggesting that, in children, SARS-CoV-2 infection may be undiagnosed. After vaccination, only receptor-binding domain (RBD)-specific IgA1 significantly increased in the saliva. Conversely, infected children had significantly higher salivary RBD-IgA2 compared to IgA1, indicating that infection more than vaccination induces a specific mucosal immune response in children. Future efforts should focus on development of vaccine technologies that also activate mucosal immunity.

Respiratory Syncytial Virus Bronchiolitis Before and After COVID-19 Pandemic: Has the Immunity Debt Been Paid Off?

BACKGROUND: Our aim was to hypothesize that the COVID-19 pandemic influenced the characteristics of viral bronchiolitis by comparing the last 3 epidemics with 3 pre-COVID-19 epidemics in infants hospitalized with bronchiolitis. METHODS: We prospectively enrolled 637 consecutive infants (median age 3.0 ± 2.1 months, 58.5% males), hospitalized for bronchiolitis during 6 consecutive annual epidemic seasons from 2017 to 2023. All parents of the children were given a structured anamnestic questionnaire. A nasopharyngeal aspirate was tested for 15 respiratory viruses. As measures of severity, we evaluated the O2 supplementation and the admission at the pediatric intensive care unit. RESULTS: A total of 166 were hospitalized with bronchiolitis in 2017-2018, 97 in 2018-2019, 69 in 2019-2020, 0 in 2020-2021, 129 in 2021-2022 and 176 in 2022-2023. Taking together the 332 bronchiolitis cases hospitalized during the 3 prepandemic seasons, they peaked between December and January; after the flat curve in 2020-2021, the cases of bronchiolitis peaked in November 2021 and in December 2022. While the 2021-2022 season registered a less severe clinical presentation, O2 supplementation and pediatric intensive care unit admissions increased in 2022-2023 with respect to the prepandemic seasons (P < 0.001). CONCLUSIONS: This study represents an important scientific demonstration of the impact of primary prevention measures on the epidemiology of viral infections; their fluctuations were related to the intensity of restrictive measures and to the changing trend of respiratory viruses. It is essential to predict the real temporal trend of bronchiolitis in order not to leave high-risk children uncovered and to guide hospitals to maintain a high level of readiness.

Age-related transcript changes in type I interferon signaling in children and adolescents with long COVID.

SARS-CoV-2 typically causes mild symptoms in children, but evidence suggests that persistent immunopathological changes may lead to long COVID (LC). To explore the interplay between LC and innate immunity, we assessed the type I interferon (IFN-I) response in children and adolescents with LC symptoms (LC; n = 28). This was compared with age-matched SARS-CoV-2 recovered participants without LC symptoms (MC; n = 28) and healthy controls (HC; n = 18). We measured the mRNA expression of IFN-I (IFN-α/ß/ε/ω), IFN-I receptor (IFNAR1/2), and ISGs (ISG15, ISG56, MxA, IFI27, BST2, LY6E, OAS1, OAS2, OAS3, and MDA5) in PBMCs collected 3-6 months after COVID-19. LC adolescents (12-17 years) had higher transcript levels of IFN-ß, IFN-ε, and IFN-ω than HC, whereas LC children (6-11 years) had lower levels than HC. In adolescents, increased levels of IFN-α, IFN-ß, and IFN-ω mRNAs were found in the LC group compared with MC, while lower levels were observed in LC children than MC. Adolescents with neurological symptoms had higher IFN-α/ß mRNA levels than MC. LC and MC participants showed decreased expression of ISGs and IFNAR1, but increased expression of IFNAR2, than HC. Our results show age-related changes in the expression of transcripts involved in the IFN-I signaling pathway in children and adolescents with LC.

Acute Bronchiolitis: The Less, the Better?

BACKGROUND: Acute bronchiolitis is a viral infection of the lower respiratory tract affecting infants aged under 12 months, variably presenting with respiratory distress, diffuse crackles and inflammatory wheezing. The main causative agent is Respiratory Syncytial Virus (RSV). The diagnosis is clinical and treatment mainly supportive. Despite the availability of more than 30 international guidelines, consistent management recommendations are lacking and considerable variability in patients' care persists among different providers. OBJECTIVE: To review and describe current knowledge about epidemiology, physiopathology, clinic, diagnosis and management of acute bronchiolitis, with particular emphasis on updated evidence and future perspectives in terms of treatment and prevention. METHODS AND RESULTS: We searched Cochrane for systematic reviews and PubMed for scientific articles published in the last 10 years, using a combination of the following search terms: "bronchiolitis", "respiratory syncytial virus", "epidemiology", "risk factors", "severity", "diagnosis", "clinic", "diagnostic imaging", "management", "asthma", "wheezing", "bronchodilator", "steroids", "hypertonic saline", "oxygen", "blood gas analysis", "HHHFNC", "rehydration", "enteral feeding", "parenteral hydration", "prevention", "vaccine" and "COVID-19 or SARS-CoV2". We accordingly performed a deep and extensive selection of the most updated and considerable literature on the matter, summarizing the most significant evidence concerning all aspects of acute bronchiolitis (epidemiology, clinic, diagnosis, management and prevention). Furthermore, we examined references and available guidelines from UK, USA, Canada, Italy and Spain. Results are extensively discussed below. CONCLUSION: Although acute bronchiolitis has been a widely known disease for decades, its therapeutic approach remained unchanged and essentially limited to respiratory and metabolic support. Despite the abundance of studies, there is no significant evidence concerning therapeutic alternatives (e.g. steroids, inhaled hypertonic solution), which are therefore not recommended. According to most recent data, "acute bronchiolitis" definition encompasses a plethora of different clinical entities related to each subject's genetic and immune predisposition. Therefore, future research should focus on the precise characterization of such subcategories in order to individualize therapeutic management and ensure the most appropriate evidence-based care.

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.

Lung function after SARS-CoV-2 infection: A prospective cohort study in children.

INTRODUCTION: Although impaired lung function after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been described in adults, it is unclear whether lung function might be altered in children, especially among asymptomatic or mildly symptomatic patients. In this study, we report the results of lung function testing performed after SARS-CoV-2 infection in a large pediatric population. METHODS: The study included 589 patients with previous confirmed SARS-CoV-2 infection aged 0-18 years. Both symptomatic and asymptomatic patients during acute infection were enrolled in the study. A spirometry was performed in all cooperating patients. RESULTS: The mean age of enrolled patients was 9.6 years and the mean time from infection to enrollment was 171 days. Spirometry was performed and deemed evaluable in 433 patients. No patient had reduced forced vital capacity (FVC) and only 14 patients (3.2%) had a forced expiratory volume in the First second (FEV1) < 80%. The mean spirometry values recorded were in the normal range. There were no statistically significant differences in spirometry values between patients with respiratory symptoms during infection and those without. Similarly, there were no differences in spirometry parameters according to the time elapsed between infection and enrollment. CONCLUSION: Lung function, according to spirometry values, does not appear to be impaired long after infection in the pediatric population. The presence of respiratory symptoms during SARS-CoV-2 infection would not represent a risk factor for impaired lung function in this cohort of patients.

E-cigarettes and youth: an unresolved Public Health concern.

The use of electronic cigarettes (e-cigarette) and vaping devices started as a potential aid for cessation and reducing the harmful consequences of cigarette smoking, mainly in the adult population. Today e-cigarette use is highly increasing in vulnerable populations, especially young and pregnant women, due to the misconception of its harmless use.Despite the growing acknowledgment in e-cigarette as a potential harmful device, and due to mixed information found concerning its beneficial aid for smokers, along with an insufficient clinical study done in human models, it is important to further evaluate the possible benefits and risks of non-combusting, vaping nicotine or non-nicotine delivery devices.In this review we tried to summarize the latest updated information found in the literature, concentrating mainly in the variety of adverse effects of e-cigarette use and its contribution for recent and future health concerns.

Serum NGF and BDNF in Long-COVID-19 Adolescents: A Pilot Study.

COVID-19 (COronaVIrus Disease 19) is an infectious disease also known as an acute respiratory syndrome caused by the SARS-CoV-2. Although in children and adolescents SARS-CoV-2 infection produces mostly mild or moderate symptoms, in a certain percentage of recovered young people a condition of malaise, defined as long-COVID-19, remains. To date, the risk factors for the development of long-COVID-19 are not completely elucidated. Neurotrophins such as NGF (Nerve Growth Factor) and BDNF (Brain-Derived Neurotrophic Factor) are known to regulate not only neuronal growth, survival and plasticity, but also to influence cardiovascular, immune, and endocrine systems in physiological and/or pathological conditions; to date only a few papers have discussed their potential role in COVID-19. In the present pilot study, we aimed to identify NGF and BDNF changes in the serum of a small cohort of male and female adolescents that contracted the infection during the second wave of the pandemic (between September and October 2020), notably in the absence of available vaccines. Blood withdrawal was carried out when the recruited adolescents tested negative for the SARS-CoV-2 ("post-infected COVID-19"), 30 to 35 days after the last molecular test. According to their COVID-19 related outcomes, the recruited individuals were divided into three groups: asymptomatics, acute symptomatics and symptomatics that over time developed long-COVID-19 symptoms ("future long-COVID-19"). As a control group, we analyzed the serum of age-matched healthy controls that did not contract the infection. Inflammatory biomarkers (TNF-α, TGF-ß), MCP-1, IL-1α, IL-2, IL-6, IL-10, IL-12) were also analyzed with the free oxygen radicals' presence as an oxidative stress index. We showed that NGF serum content was lower in post-infected-COVID-19 individuals when compared to healthy controls; BDNF levels were found to be higher compared to healthy individuals only in post-infected-COVID-19 symptomatic and future long-COVID-19 girls, leaving the BDNF levels unchanged in asymptomatic individuals if compared to controls. Oxidative stress and inflammatory biomarkers were unchanged in male and female adolescents, except for TGF-ß that, similarly to BDNF, was higher in post-infected-COVID-19 symptomatic and future long-COVID-19 girls. We predicted that NGF and/or BDNF could be used as early biomarkers of COVID-19 morbidity in adolescents.

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.

The Key Role of Lung Ultrasound in the Diagnosis of a Mature Cystic Teratoma in a Child with Suspected Difficult to Treat Pneumonia: A Case Report.

To date, the diagnosis of mediastinal teratoma and mediastinal masses relies on the use of chest X-ray and CT. Lung and thoracic ultrasound is becoming increasingly used in the diagnosis and follow-up of many lung and thoracic diseases. Here, we report the case of a mature cystic teratoma in which the performance of lung ultrasound allowed to speed up the diagnostic workup and to provide the indication for the execution of CT of the thorax allowing the diagnosis.

First COVID-19 lockdown resulted in most respiratory viruses disappearing among hospitalised children, with the exception of rhinoviruses.

AIM: Emergency room admissions have decreased globally during the COVID-19 pandemic, particularly for respiratory diseases. We evaluated hospital admissions for respiratory diseases in the first year of the Italian pandemic and compared them with the corresponding period in 2016-2017. METHODS: The study was carried out at the Sapienza University in Rome, Italy, and covered 9 March to 28 February 2020-2021 and 2016-2017. We tested 85 hospitalised children who were negative for the virus that causes COVID-19 in 2020-2021 and compared them with 476 hospitalised children from 2016-2017, as we had also tested nasal washing samples for 14 respiratory viruses during that period. RESULTS: Hospitalisations for acute respiratory tract infections were 82.2% lower in 2020-2021 than 2016-2017. The respiratory syncytial virus (RSV) and several other viruses were detected less frequently during the pandemic. An extraordinary finding was that rhinoviruses remained seasonal. In 2020-2021, we detected a virus in 54.1% of the hospitalised children: rhinoviruses in 41, RSV in 4 and other viruses in 1. This was significantly lower than the 71.6% in 2016-2017: RSV in 130, rhinoviruses in 128 and other viruses in 83. CONCLUSION: Pandemic measures dramatically reduced childhood respiratory infections, particularly RSV, but were less effective at reducing rhinoviruses.

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.

During the COVID-19 pandemic where has respiratory syncytial virus gone?

The diffusion of the SARS-CoV-2 virus and the implementation of restrictive measures led to a drastic reduction of respiratory syncytial virus (RSV) diffusion. Few RSV cases have been detected worldwide, even after the removal of the restrictions. We review the current literature and present possible explanations on why there has been a significant reduction of RSV detection during the COVID-19 pandemic. We also hypothesize what may happen when RSV begins to circulate again. The increase of an immunologically naïve population, with infants born from mothers who have not reinforced their immunity to RSV, could lead to greater RSV epidemics in the coming seasons. It is crucial to prepare the scientific community and to keep RSV surveillance active to avoid dramatic consequences.

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.

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).

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.

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.

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.