Impact of public health measures and new introducing variants on Respiratory syncytial virus recrudescence in Taiwan during the COVID-19 pandemic.

OBJECTIVES: Respiratory syncytial virus (RSV) causes clinically significant distress in children and adults. Non-pharmaceutical interventions against SARS-CoV-2 have affected the seasonal activity of common respiratory pathogens. This seems exceptionally true regarding RSV's seasonal circulation, hence we have investigated the changes in the epidemiology of RSV in Taiwan during the pandemic. MATERIALS: A prospective surveillance of RSV among hospitalized children was carried out between 2020 and 2022 in central Taiwan. Of all PCR-detected RSV, genotype and evolutionary analysis were further investigated. Demographics and clinical features were compared between each outbreak. RESULTS: Throughout the consecutive three years of the SARS-CoV-2 pandemic, RSV outbreaks took place in Taiwan first in 2020 and a second time in 2022. We enrolled 80 and 105 hospitalized child cases, in each surge respectively. The RSV G protein genomic analysis revealed that RSV ON1 and RSV BA9 were separately contributing to these two outbreaks, and evolutionary evidence indicated these RSV variants are new to Taiwan, with their own featured sets of mutations. Clinically, a shift in age of RSV infected children was found, but the clinical severity was not worse and remained independent of RSV genotype. CONCLUSIONS: There were two delayed RSV surges after the relaxation of public measures during the pandemic in Taiwan, and both outbreaks were driven by new RSV genetic variants rather than cryptic circulation of the previous genetic clusters in Taiwan. These findings highlight the importance of continued surveillance on the trend and evolution of RSV after the COVID-19 pandemic.

Clinical characteristics and differential cytokine expression in hospitalized Taiwanese children with respiratory syncytial virus and rhinovirus bronchiolitis.

BACKGROUND: Viral bronchiolitis presents a heterogeneous spectrum. In this study, we investigated the clinical characteristics and the cytokines/chemokines profiles among respiratory syncytial virus (RSV), rhinovirus (RV), and their dual infection in Taiwanese children with viral bronchiolitis. METHOD: This study was conducted between October 2014 and June 2017. Viral etiology was identified using a Luminex respiratory virus panel and blood cytokines were evaluated using a MILLIPLEX MAP Human Cytokine/Chemokine Panel. Cytokine/Chemokine expressions were compared by clinical severity, steroid treatment, and viral entities. RESULTS: A total of 184 patients were evaluated; at least one respiratory virus was identified in 163 (88.6%) patients. RSV and RV were the two leading viral etiologies, with 25.5% and 17.3%, respectively. RV bronchiolitis has a comparable severity to RSV but is more common in children of an older age with a history of recurrent wheezing and blood eosinophilia. Decreased tumor necrosis factor-alpha (TNF-α) and interferon gamma (INF-γ) levels were correlated with clinical severity. Patients infected with RV exhibited higher levels of Interleukin (IL)-22, IL-23, IL-25, IL-31, and IL-33 (p < 0.05), whereas those with RSV had higher levels of TNF-α, INF-γ, and IL-10 (p < 0.05). Systemic steroid treatment was associated with higher expressions of IL-4, IL-8, IL-13, and MIP-1α levels (p < 0.05). Cluster analysis revealed a high correlation of IL-33 and IL-31(R2 = 0.9731, p < 0.0001). CONCLUSION: Different viral infections elicited the characteristic clinical presentation and immune profiles in bronchiolitis. Our findings also highlight the role of the IL-33/IL-31 axis in the immunopathogenesis of bronchiolitis.

Delayed respiratory syncytial virus outbreak in 2020 in Taiwan was correlated with two novel RSV-A genotype ON1 variants.

BACKGROUND: Human respiratory syncytial virus (RSV) is a leading pathogen of acute respiratory tract disease among infants and young children. Compared with previous seasons, RSV outbreaks in Taiwan during the 2020-2021 season were delayed because of COVID-19 mitigation measures. We conducted this study to determine the association of viral factors with clinical characteristics of preschool children with RSV infection. METHODS: We performed a molecular epidemiology analysis of RSV among inpatient preschool children in Taiwan. In 80 nasopharyngeal samples positive for RSV, we sequenced and analyzed viral genotypes according to patient data. Patients' clinical data were obtained from medical files, and their clinical profiles were compared with those of RSV cases recorded during the 2014-2017 seasons. RESULTS: Phylogenetic analysis revealed that among the RSV-positive samples, all RSV strains identified during the 2020-2021 season belonged to the ON1 genotype. Most of the Taiwan ON1 strains were categorized into two well-supported clusters with distinct G protein amino acid substitution patterns that had never been demonstrated previously. Furthermore, the proportion of cases among children aged >24 months increased (P < 0.001). Compared with patients infected during the 2014-2017 seasons, patients infected during the 2020-2021 season were hospitalized for shorter days from hospital admission to dereference (P = 0.004) and had a greater need for oxygen supplements (P = 0.021) and systemic steroid therapy (P = 0.026). CONCLUSION: The delayed 2020-2021 RSV outbreak in Taiwan was caused by two novel RSV ON1.1 variants. How the change in RSV epidemiology affects future RSV outbreaks warrants exploration.

Early Bronchiolitis Contributes to Preschool Asthma.

This study aims to analyze whether bronchiolitis in children younger than one-year-old contributes to subsequent asthma. Medical data were retrieved from the National Health Insurance Research Database of Taiwan. Participants were divided into study (N = 65,559) and control (N = 49,656) groups, depending on whether they had early bronchiolitis. Incidences of asthma, potential comorbidities, and associated medical conditions were compared. The incidence of childhood asthma was significantly higher in the study group (aHR = 1.127, 95% CI: 1.063-1.195). Children with bronchiolitis hospitalization displayed higher asthma risk in the period between two and four years of age. The risk diminished as the children grew up. No relevant synergistic effects were found between bronchiolitis and atopic dermatitis. In conclusion, bronchiolitis before one year of age exhibits predictive value for development of preschool asthma, especially in children with bronchiolitis hospitalizations.

Influence of prolonged storage process, pasteurization, and heat treatment on biologically-active human milk proteins.

OBJECTIVES: The bioactive proteins in human milk may be influenced by prolonged storage process, pasteurization, and heat treatment. This study was conducted to evaluate the effects of these procedures. MATERIALS AND METHODS: Three forms of human milk - freshly expressed, frozen at -20°C for a prolonged duration, and pasteurized milk - were collected from 14 healthy lactating mothers and a milk bank. The concentrations of major bioactive proteins (secretory immunoglobulin A, lactoferrin, lysozyme, and leptin) were quantified using enzyme-linked immunosorbent assay kits. Changes in these proteins by heat treatment at 40°C or 60°C for 30 minutes were further evaluated. RESULTS: The mean concentrations of lactoferrin and secretory immunoglobulin A were significantly reduced by 66% and 25.9%, respectively, in pasteurized milk compared with those in freshly-expressed milk. Heat treatment at 40°C or 60°C did not cause significant changes in lactoferrin and secretory immunoglobulin A, but there was an apparent increase in lysozyme (p = 0.016). There were no significant differences in leptin level among these three forms of milk prior to (p = 0.153) or after heat treatment (p = 0.053). CONCLUSION: Various freezing/heating/pasteurization processes applied to human milk prior to delivery to neonates could affect the concentration of immunomodulatory proteins, especially lactoferrin, secretory immunoglobulin A, and lysozyme. Leptin was unaffected by the various handling processes tested. Fresh milk was found to be the best food for neonates. Further studies are warranted to evaluate the functional activity of these proteins and their effects on infants' immunological status.

Refractory ventricular tachycardia in a long QT syndrome child successfully controlled by left cardiac sympathetic denervation.

Long QT syndrome is a congenital disorder accompanied by a high incidence of sudden cardiac death. ß-adrenergic blockade is the therapy of choice, and it is successful in 75-80% of patients. However, for those in whom refractory arrhythmia or cardiac events are not prevented by medication, the literature suggests that left cardiac sympathetic denervation may be useful. Here we present a girl 20 months of age with refractory ventricular tachycardia due to long QT syndrome successfully treated by left cardiac sympathetic denervation. There was no significant complication.