Respiratory Illness In Children Research Articles

Safety and Immunogenicity of an mRNA-Based hMPV/PIV3 Combination Vaccine in Seropositive Children.

Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) are common respiratory illnesses in children. The safety and immunogenicity of an investigational mRNA-based vaccine, mRNA-1653, encoding membrane-anchored fusion proteins of hMPV and PIV3, was evaluated in hMPV/PIV3-seropositive children. In this phase 1b randomized, observer-blind, placebo-controlled, dose-ranging study, hMPV/PIV3-seropositive children were enrolled sequentially into 2 dose levels of mRNA-1653 administered 2 months apart; children aged 12 to 36 months were randomized (1:1) to receive 10-μg of mRNA-1653 or placebo and children aged 12 to 59 months were randomized (3:1) to receive 30-μg of mRNA-1653 or placebo. Overall, 27 participants aged 18 to 55 months were randomized; 15 participants received 10-μg of mRNA-1653 (n = 8) or placebo (n = 7), whereas 12 participants received 30-μg of mRNA-1653 (n = 9) or placebo (n = 3). mRNA-1653 was well-tolerated at both dose levels. The only reported solicited local adverse reaction was tenderness at injection site; solicited systemic adverse reactions included grade 1 or 2 chills, irritability, loss of appetite, and sleepiness. A single 10-μg or 30-μg mRNA-1653 injection increased hMPV and PIV3 neutralizing antibody titers (geometric mean fold-rise ratio over baseline: hMPV-A = 2.9-6.1; hMPV-B = 6.2-13.2; PIV3 = 2.8-3.0) and preF and postF binding antibody concentrations (geometric mean fold-rise ratio: hMPV preF = 5.3-6.1; postF = 4.6-6.5 and PIV3 preF = 13.9-14.2; postF = 11.0-12.1); a second injection did not further increase antibody levels in these seropositive children. Binding antibody responses were generally preF biased. mRNA-1653 was well-tolerated and boosted hMPV and PIV3 antibody levels in seropositive children aged 12 to 59 months, supporting the continued development of mRNA-1653 or its components for the prevention of hMPV and PIV3.

Evolutionary trends of respiratory syncytial viruses: Insights from large-scale surveillance and molecular dynamics of G glycoprotein

Human respiratory syncytial virus (RSV) is an underlying cause of lower respiratory illnesses in children, elderly and immunocompromised adults. RSV contains multiple structural and non-structural proteins with two major glycoproteins that control the initial phase of infection, fusion glycoprotein and the attachment (G) glycoprotein. G protein attaches to the ciliated cells of airways initiating the infection. The hypervariable G protein plays a vital role in evolution of RSV strains. We employed multiple bioinformatics tools on systematically accessed large-scale data to evaluate mutations, evolutionary history, and phylodynamics of RSV. Mutational analysis of central conserved region (CCR) on G protein-coding sequences between 163 and 189 positions revealed frequent mutations at site 178 in human RSV (hRSV) A while arginine to glutamine substitutions at site 180 positions in hRSV B, remained prevalent from 2009 to 2014. Phylogenetic analysis indicates multiple signature mutations within G protein responsible for diversification of clades. The USA and China have highest number of surveillance records, followed by Kenya. Markov Chain Monte Carlo Bayesian skyline plot revealed that RSV A evolved steadily from 1990 to 2000, and rapidly between 2003 and 2005. Evolution of RSV B continued from 2003 to 2022, with a high evolution stage from 2016 to 2020. Throughout evolution, cysteine residues maintained their strict conserved states while CCR has an entropy value of 0.0039(±0.0005). This study concludes the notion that RSV G glycoprotein is continuously evolving while the CCR region of G protein maintains its conserved state providing an opportunity for CCR-specific monoclonal antibodys (mAbs) and inhibitors as potential candidates for immunoprophylaxis.

After COVID-19: preparing staff for future surges in respiratory illness in children and improving well-being.

The coronavirus disease 2019 (COVID-19) pandemic was a challenging experience for children and young people's services, and the workforce. The Valuing All Staff Together programme was a one-year project hosted by the North West Paediatric Critical Care, Surgery in Children, Long Term Ventilation Operational Delivery Network to support teams caring for children and young people to reflect on their experiences of the COVID-19 pandemic. Using an online survey, focus groups and interviews, it gave staff the opportunity to explore and understand the effects of the pandemic and the subsequent surge in demand, including how these affected services and the emotional health and well-being of staff. This would enable better preparation for future surges in respiratory illness in terms of learning, training and development. This article describes the programme's aim, method and findings, and the main recommendations for practice.

Ayurveda Approach towards Respiratory Illness in Children

Abstract: Preventable diseases such as pneumonia, diarrhoea, and other infections are the leading causes of morbidity in children, therefore each child's physical and emotional needs differ according to their age, personality, and developmental stage. 15% of children suffer from RRTIs. Predisposing variables include immune system inadequacies, anatomic and functional changes in the respiratory tract, air pollution exposure, and poor socioeconomic conditions. RRTIs are a prevalent disorder, especially in children under the age of six, and are usually caused by poor environmental conditions. 60% of patients had bacterial growth but RRIs begin as a viral respiratory tract infection and symptoms of infection for at least 10 days.i URTI is most common known cause of morbidity in children, which causes limiting daily activities and causing school absence.

Seasonality, Clinical Characteristics, and Outcomes of Respiratory Syncytial Virus Disease by Subtype Among Children Aged

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illnesses in children. RSV can be broadly categorized into 2 major subtypes: A and B. RSV subtypes have been known to cocirculate with variability in different regions of the world. Clinical associations with viral subtype have been studied among children with conflicting findings such that no conclusive relationships between RSV subtype and severity have been established. During 2016-2020, children aged <5 years were enrolled in prospective surveillance in the emergency department or inpatient settings at 7 US pediatric medical centers. Surveillance data collection included parent/guardian interviews, chart reviews, and collection of midturbinate nasal plus/minus throat swabs for RSV (RSV-A, RSV-B, and untyped) using reverse transcription polymerase chain reaction. Among 6398 RSV-positive children aged <5 years, 3424 (54%) had subtype RSV-A infections, 2602 (41%) had subtype RSV-B infections, and 272 (5%) were not typed, inconclusive, or mixed infections. In both adjusted and unadjusted analyses, RSV-A-positive children were more likely to be hospitalized, as well as when restricted to <1 year. By season, RSV-A and RSV-B cocirculated in varying levels, with 1 subtype dominating proportionally. Findings indicate that RSV-A and RSV-B may only be marginally clinically distinguishable, but both subtypes are associated with medically attended illness in children aged <5 years. Furthermore, circulation of RSV subtypes varies substantially each year, seasonally and geographically. With introduction of new RSV prevention products, this highlights the importance of continued monitoring of RSV-A and RSV-B subtypes.

Impact of ambient air pollution and socio-environmental factors on the health of children younger than 5 years in India: a population-based analysis

Ambient air pollution and household environmental factors affect child health, particularly in low-income and middle-income countries. This study aimed to investigate the association between ambient air pollution (PM2·5) levels, socio-environmental factors (including household wealth, housing quality measures, smoking status), and the occurrence of respiratory illness in Indian children. In this retrospective and observational study, we analysed data from India's National Family Health Survey (NFHS-5, 2019-2021) combined with NASA's Global Annual PM2·5 Grids database. Bivariate and multivariable generalized additive models were employed to examine associations between key social-environmental factors and respiratory illness in children younger than 5 years. We analysed data from 224,214 children younger than 5 years, representing 165,561 families from 29,757 geographic clusters. Our results showed extremely high annual PM2·5 levels throughout India (median 63·4·g/m3, IQR 41·9-81·6), with higher exposure for rural and impoverished families. In bivariate analyses, PM2·5 was significantly associated with reported respiratory illness (p<0·001). Using generalized additive models and after accounting for key social and environmental factors, a monotonic increasing and non-linear relationship was observed between PM2·5 and respiratory illness (p<0·001), with increased likelihood of illness observed even at values near and below India's National Ambient Air Quality Standards of 40μg/m3. The study highlights the significant association of social-environmental conditions with health outcomes among young children in India. Efforts specifically targeting ambient air pollution and child health during monsoon season could have significant health benefits among this population and help achieve the goal of ending preventable deaths of children younger than 5 years. National Institutes of Health (NIH T-32-HL139443-3).

2655. Phase 1 Safety and Immunogenicity Results of Two Investigational mRNA Vaccines, mRNA-1345, a Respiratory Syncytial Virus Vaccine, and mRNA-1653, a Human Metapneumovirus and Parainfluenza Virus Type 3 Combination Vaccine in Seropositive Young Children

Abstract Background Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza virus type 3 (PIV3) are common respiratory illnesses in children. Two investigational vaccines, mRNA-1345, encoding the RSV prefusion stabilized F (preF) glycoprotein, and mRNA-1653, encoding the hMPV and PIV3 F glycoproteins, are in clinical trials. Methods Two phase 1, randomized, observer-blind, placebo-controlled trials in children aged 12-59 months assessed safety and immunogenicity of mRNA-1345 (NCT04528719) and mRNA-1653 (NCT04144348). In the mRNA-1345 trial, RSV-seropositive children (N=46) were randomized to receive 3 doses of mRNA-1345 (15 µg or 30 µg) or placebo 2 months apart. In the mRNA-1653 trial, hMPV- and PIV3-seropositive children (N=27) were randomized to receive 2 doses of mRNA-1653 (10 µg or 30 µg) or placebo 2 months apart. Interim data through Month (M) 5 for mRNA-1345 and M3 for mRNA-1653 are reported. Results mRNA-1345 and mRNA-1653 were well-tolerated. The most frequently reported solicited local adverse reaction (AR) was tenderness at injection site (mRNA-1345, 35.7%-71.4%; placebo, 26.7%-42.9% and mRNA-1653, 44.4%-60.0%; placebo, 12.5%-30.0%); solicited systemic ARs (mRNA-1345, 12.5%-53.3%; placebo, 33.3%-50.0% and mRNA-1653, 33.3%-55.6%; placebo, 12.5%-60.0%) were mostly grade 1/2. One mRNA-1345 injection boosted RSV neutralizing antibody (nAb) titers (geometric mean fold rise [GMFR] over baseline: RSV-A=18.9-34.9; RSV-B=7.2-14.3) and RSV preF and postF binding antibody (bAb) concentrations (GMFR: preF=13.9-26.5; postF=9.3-16.0); additional injections did not further elevate antibody levels (Fig 1A and 2A). One mRNA-1653 injection boosted hMPV and PIV3 nAb titers (GMFR over baseline: hMPV-A=2.9-6.1; hMPV-B=6.2-13.2; PIV3=2.8-3.0) and preF and postF bAb concentrations (GMFR: hMPV preF=5.3-6.1; postF=4.6-6.5 and PIV3 preF=13.9-14.2; postF=11.0-12.1); a second injection did not further increase antibody levels (Fig 1B,C and 2B,C). In both trials, bAb responses were generally preF biased. Conclusion In seropositive children aged 12-59 months, mRNA-1345 and mRNA-1653 were well-tolerated and boosted RSV and hMPV plus PIV3 antibodies, respectively, supporting their continued development and that of a combination RSV and hMPV vaccine. Disclosures Matthew D. Snape, MBBS, MD, FRCPCH, FPM, FMedSci, Moderna Biotech UK, Inc.,: Employee|Moderna Biotech UK, Inc.,: Stocks/Bonds Sabine Schnyder Ghamloush, MD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Grace L. Chen, MD, MPH, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Rakesh Dhar, MD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Runa Mithani, PharmD, Moderna, Inc: Employee|Moderna, Inc: Stocks/Bonds Vinicius Righi, PharmD, MBA, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Louie Morsy, BS, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Archana Kapoor, PhD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Bethany Girard, Ph.D., Moderna, Inc.: salary|Moderna, Inc.: Stocks/Bonds Laila El Asmar, PhD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Christine A. Shaw, PhD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds

Very high intensity of the bronchiolitis epidemic during the 2022-2023 season in France

Abstract Background During epidemic seasons, bronchiolitis affects young children with a large burden in emergency departments (EDs). Following the beginning of the COVID-19 pandemic and 2 perturbed seasons, the aim of this study was to assess the burden of bronchiolitis in EDs in terms of visits and post-discharge hospitalisations in 2022-23 compared with the pre-COVID seasons. Methods Santé publique France, collects ED data through OSCOUR® (95% of French ED visits). ED visits with a medical diagnosis of bronchiolitis (based on ICD-10 codes) in children under 2 years of age (yo) were included. The burden of the 2022-23 epidemic season (from 2022-W36 to 2023-W16) was compared with that of the pre-COVID seasons (2015-16 to 2019-20), by age group, in terms of visits and hospitalisations after discharge, in particular in intensive care units (ICUs) (annual data and means). Results In 2022-23, 99,864 ED visits for bronchiolitis and 31,505 post-discharge hospitalisations were registered for children under 2 yo (vs. respectively +49% and +44% compared to the pre-COVID seasons). It represented 15% of all ED visits and 33% of all hospitalisations after discharge of this age group (vs. 10% and 23% pre-COVID). Among children under 1 year, distribution of bronchiolitis ED visits by age group remained relatively stable in comparison with pre-COVID seasons. For children under 6 months, bronchiolitis accounted for 27% of all ED visits (19% pre-COVID), 45% of all hospitalisations (35% pre-COVID) and more than 70% of hospitalisations referred in ICU during 7 weeks (2 weeks pre-COVID). Conclusions The 2022-2023 bronchiolitis epidemic was of extreme intensity in France with a highest impact than for pre-covid seasons and leading to saturation of EDs. These findings were consistent with an increase in respiratory illness in children during the 2022-23 winter season, and raised questions about the impact of the COVID-19 pandemic on their epidemiology and a potential decrease of immunity. Key messages • Beside a very high intensity for the 2022-23 bronchiolitis epidemic, distribution of ED visits by age group remained relatively stable among children under 1 year. • In 2022-2023, among children under 6 months, during nearly two months (7 weeks), more than 70% of hospitalizations after discharged referred in ICU were due to bronchiolitis.

Comparative analysis of RSV-related hospitalisations in children and adults over a 7 year-period before, during and after the COVID-19 pandemic.

RSV is an important cause for respiratory illness in children and the elderly. We analysed RSV seasons since 2016 in both age groups for differences, similarities and timely associations before, during and after the COVID-19 pandemic. We studied epidemiological and clinical features of seven consecutive RSV seasons since 2016 retrospectively in children and adults who were systematically monitored for RSV infections by PCR when hospitalized in Regensburg, Germany. Data from 1903 RSV positive, hospitalised patients were analysed (1446 children, 457 adults). We observed a complete absence of RSV associated hospitalizations in season 2020/2021. While in the season of 2021/2022, RSV associated hospitalizations in children returned to considerable numbers earlier than expected, hospitalizations in the elderly were still mitigated during that season in temporal association with the continuation of NPI measures for COVID-19 in the elderly until summer of 2022. Overall, children were hospitalized more often for RSV, while the elderly showed more severe outcomes. RSV hospitalisations continuously increase in both age groups, following a bi-annual pattern of severe and less severe seasons, which was not altered by the COVID-19 pandemic. We demonstrate the relation between RSV waves in children and the elderly. NPI measures may protect the elderly from RSV infections and epidemiological data could be used to predict RSV waves early enough to prepare countermeasures.

Efficacy of an isoxazole-3-carboxamide analog of pleconaril in mouse models of Enterovirus-D68 and Coxsackie B5

Enteroviruses (EV) cause a number of life-threatening infectious diseases. EV-D68 is known to cause respiratory illness in children that can lead to acute flaccid myelitis. Coxsackievirus B5 (CVB5) is commonly associated with hand-foot-mouth disease. There is no antiviral treatment available for either. We have developed an isoxazole-3-carboxamide analog of pleconaril (11526092) which displayed potent inhibition of EV-D68 (IC50 58 nM) as well as other enteroviruses including the pleconaril-resistant Coxsackievirus B3-Woodruff (IC50 6–20 nM) and CVB5 (EC50 1 nM). Cryo-electron microscopy structures of EV-D68 in complex with 11526092 and pleconaril demonstrate destabilization of the EV-D68 MO strain VP1 loop, and a strain-dependent effect. A mouse respiratory model of EV-D68 infection, showed 3-log decreased viremia, favorable cytokine response, as well as statistically significant 1-log reduction in lung titer reduction at day 5 after treatment with 11526092. An acute flaccid myelitis neurological infection model did not show efficacy. 11526092 was tested in a mouse model of CVB5 infection and showed a 4-log TCID50 reduction in the pancreas. In summary, 11526092 represents a potent in vitro inhibitor of EV with in vivo efficacy in EV-D68 and CVB5 animal models suggesting it is worthy of further evaluation as a potential broad-spectrum antiviral therapeutic against EV.

Hydrocarbon Stapling-Improved Coupled Folding-Upon-Binding of Peptide-Mediated Interaction between the Nucleocapsid and Phosphoprotein of Human Orthopneumovirus

Human orthopneumovirus (OPV) is a common respiratory virus that mostly causes respiratory illness in children. Development of therapeutic strategies to treat OPV infection has attracted considerable interest in the medicinal and biological communities. Over the past decades, significant effects have been addressed on disrupting membrane fusion events by targeting viral fusogenic glycoprotein (F-protein) with chemical small-molecule fusion inhibitors. Here, we focus on the rational design of biologic peptide inhibitors to disrupt the peptide-mediated interaction (PMI) between phosphoprotein (P-protein) and nucleoprotein (N-protein) involved in OPV genomic ribonucleoprotein complex. It is revealed that the core 9-mer peptide segment (C-peptide) derived from the C-terminal tail of P-protein is intrinsically disordered in an unbound state but would be structured into an ordered helical conformation when bound to N-protein, representing a biophysical process known as coupled folding-upon-binding. We demonstrated that the process is a compromise between the favorable enthalpy contribution and unfavorable entropy penalty, thus rendering the weak and transient nature of PMI, which could therefore be readily disrupted by competitive agents. Hydrocarbon stapling strategy was used to constrain the helical conformation of C-peptide in an unbound state by chemically introducing an all-hydrocarbon bridge spanning two [Formula: see text] residues of C-peptide. The stapling is observed to considerably enhance the helical propensity of peptide in an unbound state and to effectively improve the binding affinity of peptide to N-protein. Structural modeling analysis suggests that the stapled counterparts can bind to the active site of N-protein in a similar mode with unstapled C-peptide, where the stapled peptide is folded into a helical-like conformation, its anchor residue Phe241 deeply roots in a small druggable pocket of the active site, and the all-hydrocarbon bridge, as designed, is out of N–C complex interface to avoid disrupting the complex interaction.

DeepBreath—automated detection of respiratory pathology from lung auscultation in 572 pediatric outpatients across 5 countries

The interpretation of lung auscultation is highly subjective and relies on non-specific nomenclature. Computer-aided analysis has the potential to better standardize and automate evaluation. We used 35.9 hours of auscultation audio from 572 pediatric outpatients to develop DeepBreath : a deep learning model identifying the audible signatures of acute respiratory illness in children. It comprises a convolutional neural network followed by a logistic regression classifier, aggregating estimates on recordings from eight thoracic sites into a single prediction at the patient-level. Patients were either healthy controls (29%) or had one of three acute respiratory illnesses (71%) including pneumonia, wheezing disorders (bronchitis/asthma), and bronchiolitis). To ensure objective estimates on model generalisability, DeepBreath is trained on patients from two countries (Switzerland, Brazil), and results are reported on an internal 5-fold cross-validation as well as externally validated (extval) on three other countries (Senegal, Cameroon, Morocco). DeepBreath differentiated healthy and pathological breathing with an Area Under the Receiver-Operator Characteristic (AUROC) of 0.93 (standard deviation [SD] ± 0.01 on internal validation). Similarly promising results were obtained for pneumonia (AUROC 0.75 ± 0.10), wheezing disorders (AUROC 0.91 ± 0.03), and bronchiolitis (AUROC 0.94 ± 0.02). Extval AUROCs were 0.89, 0.74, 0.74 and 0.87 respectively. All either matched or were significant improvements on a clinical baseline model using age and respiratory rate. Temporal attention showed clear alignment between model prediction and independently annotated respiratory cycles, providing evidence that DeepBreath extracts physiologically meaningful representations. DeepBreath provides a framework for interpretable deep learning to identify the objective audio signatures of respiratory pathology.

EV-D68 virus-like particle vaccines elicit cross-clade neutralizing antibodies that inhibit infection and block dissemination.

Enterovirus D68 (EV-D68) causes severe respiratory illness in children and can result in a debilitating paralytic disease known as acute flaccid myelitis. No treatment or vaccine for EV-D68 infection is available. Here, we demonstrate that virus-like particle (VLP) vaccines elicit a protective neutralizing antibody against homologous and heterologous EV-D68 subclades. VLP based on a B1 subclade 2014 outbreak strain elicited comparable B1 EV-D68 neutralizing activity as an inactivated viral particle vaccine in mice. Both immunogens elicited weaker cross-neutralization against heterologous viruses. A B3 VLP vaccine elicited more robust neutralization of B3 subclade viruses with improved cross-neutralization. A balanced CD4+ T helper response was achieved using a carbomer-based adjuvant, Adjuplex. Nonhuman primates immunized with this B3 VLP Adjuplex formulation generated robust neutralizing antibodies against homologous and heterologous subclade viruses. Our results suggest that both vaccine strain and adjuvant selection are critical elements for improving the breadth of protective immunity against EV-D68.

Epidemiologic, clinical, and genetic characteristics of influenza C virus infections among outpatients and inpatients in Sendai, Japan from 2006 to 2020.

Influenza C virus is a pathogen that causes acute respiratory illness in children. The clinical information about this virus is limited because of the small number of isolated viruses compared to influenza A or B viruses. A total of 60 influenza C viruses were isolated by clinical tests using cell culture methods conducted in one hospital and one clinic during the 15 years from 2006 to 2020. These 60 cases were retrospectively analyzed by comparing outpatients and inpatients. Moreover, isolated viruses were analyzed for genomic changes during the study period. All were younger than 7 years, and 73% of inpatients (19 out of 26) were under 2 years of age. A significant difference was found in the frequency of pneumonia, accounting for 45% and 4% of inpatients and outpatients, respectively. Most of the viruses isolated from 2006 to 2012 belonged to the S/A sublineage of the C/Sao Paulo lineage, but three sublineage viruses, including the S/A sublineage with K190N mutation, S/V sublineage, and C/Kanagawa lineage, have cocirculated since 2014. Moreover, S/A sublineage viruses were undergoing reassortment since 2014, suggesting significant changes in the virus, both antigenically and genetically. Of the 10 strains from patients with pneumonia, 7 were in the S/A sublineage, which had circulated from 2006 to 2012. Infants under 2 years of age were more likely to be hospitalized with pneumonia. The genomic changes that occurred in 2014 were suggested to affect the ability of the virus to spread.

How to spot the red flags and other warning signs for respiratory illness in children

There has been a recent resurgence in traditional respiratory infections and nurses are encouraged to be inquisitive in their interactions with children and families

Rhinovirus C causes heterogeneous infection and gene expression in airway epithelial cell subsets

Rhinoviruses (RV) infect ciliated airway epithelial cells and RV nonstructural proteins quickly inhibit and divert cellular processes for viral replication. Yet, the epithelium can mount a robust innate antiviral immune response. Therefore, we hypothesized that uninfected cells contribute significantly to the antiviral immune response in the airway epithelium. Using single-cell RNA sequencing, we demonstrate that both infected and uninfected cells upregulate antiviral genes (e.g., MX1, IFIT2, IFIH1, OAS3) with nearly identical kinetics, while uninfected non-ciliated cells are the primary source of proinflammatory chemokines. Furthermore, we identified a subset of highly infectable ciliated epithelial cells with minimal interferon responses and determined that interferon responses originate from distinct subsets of ciliated cells with moderate viral replication. These findings suggest that the composition of ciliated airway epithelial cells and coordinated responses of infected and uninfected cells could determine the risk of more severe viral respiratory illnesses in children with asthma, COPD, and genetically susceptible individuals.

Approach to Acute Respiratory Illness in Children with Hematological Malignancy: A Prospective Study Evaluating Utility of CT Scan

Abstract Introduction Various pulmonary complications can occur in children with hematological malignancies including both infection and malignant disease infiltration of pulmonary parenchyma. Objectives To assess the role of CT scan in determining the etiology of acute pulmonary complications in children with hematological malignancies. Materials and Methods All children &lt; 17 years with newly diagnosed hematological malignancy with respiratory symptoms (Group A) along with children who developed fever with persistent respiratory symptoms as well as worsening chest radiographs during treatment (Group B) and underwent CECT thorax, from February 2019 to July 2020 were enrolled. The final diagnosis was made on the basis of clinical history, laboratory as well as radiological investigations and treatment response. Results Thirty-seven children with mean age of 7.5 ± 3.5 years and male to female ratio of 1.3:1 who underwent CECT thorax were included in our study. For newly diagnosed cases, i.e., Group A (n = 8), the most common cause of respiratory symptoms as identified on CECT thorax was pulmonary tumoral infiltration (n = 5) followed by tuberculosis (n = 3). However, in Group B (n = 29) the cause of persistent respiratory symptoms was identified as infection (n = 17) followed by leukemic infiltration (n = 12). Thus, chest CT could accurately identify pulmonary tuberculosis, fungal pneumonia, bacterial infection, and pulmonary tumoral infiltrates. Conclusion CT scan can be used as an adjunctive tool for prompt diagnosis and management of pulmonary complications in children with persistent respiratory symptoms as they are often non-specific.

Longitudinal Household Assessment of Respiratory Illness in Children and Parents During the COVID-19 Pandemic

In the early COVID-19 pandemic, SARS-CoV-2 testing was only accessible and recommended for symptomatic persons or adults. This restriction hampered assessment of the true incidence of SARS-CoV-2 infection in children as well as detailed characterization of the SARS-CoV-2 disease spectrum and how this spectrum compared with that of other common respiratory illnesses. To estimate the community incidence of SARS-CoV-2 infection in children and parents and to assess the symptoms and symptom severity of respiratory illness episodes involving SARS-CoV-2-positive test results relative to those with SARS-CoV-2-negative test results. This cohort study randomly selected Dutch households with at least 1 child younger than 18 years. A total of 1209 children and adults from 307 households were prospectively followed up between August 25, 2020, and July 29, 2021, covering the second and third waves of the COVID-19 pandemic. Participation included SARS-CoV-2 screening at 4- to 6-week intervals during the first 23 weeks of participation (core study period; August 25, 2020, to July 29, 2021). Participants in all households finishing the core study before July 1, 2021, were invited to participate in the extended follow-up and to actively report respiratory symptoms using an interactive app until July 1, 2021. At new onset of respiratory symptoms or a SARS-CoV-2 positive test result, a household outbreak study was initiated, which included daily symptom recording, repeated polymerase chain reaction testing (nose-throat swabs and saliva and fecal samples), and SARS-CoV-2 antibody measurement (paired dried blood spots) in all household members. Outbreaks, households, and episodes of respiratory illness were described as positive or negative depending on SARS-CoV-2 test results. Data on participant race and ethnicity were not reported because they were not uniformly collected in the original cohorts and were therefore not representative or informative. SARS-CoV-2-positive and SARS-CoV-2-negative respiratory illness episodes. Age-stratified incidence rates, symptoms, and symptom severity for SARS-CoV-2-positive and SARS-CoV-2-negative respiratory illness episodes. Among 307 households including 1209 participants (638 female [52.8%]; 403 [33.3%] aged <12 years, 179 [14.8%] aged 12-17 years, and 627 [51.9%] aged ≥18 years), 183 household outbreaks of respiratory illness were observed during the core study and extended follow-up period, of which 63 (34.4%) were SARS-CoV-2 positive (59 outbreaks [32.2%] during the core study and 4 outbreaks [2.2%] during follow-up). SARS-CoV-2 incidence was similar across all ages (0.24/person-year [PY]; 95% CI, 0.21-0.28/PY). Overall, 33 of 134 confirmed SARS-CoV-2 episodes (24.6%) were asymptomatic. The incidence of SARS-CoV-2-negative respiratory illness episodes was highest in children younger than 12 years (0.94/PY; 95% CI, 0.89-0.97/PY). When comparing SARS-CoV-2-positive vs SARS-CoV-2-negative respiratory illness episodes in children younger than 12 years, no differences were observed in number of symptoms (median [IQR], 2 [2-4] for both groups), symptom severity (median [IQR] maximum symptom severity score, 6 [4-9] vs 7 [6-13]), or symptom duration (median [IQR], 6 [5-12] days vs 8 [4-13] days). However, among adults, SARS-CoV-2-positive episodes had a significantly higher number (median [IQR], 6 [4-8] vs 3 [2-4]), severity (median [IQR] maximum symptom severity score, 15 [9-19] vs 7 [6-11]), and duration (median [IQR] 13 [8-29] days vs 5 [3-11] days; P < .001 for all comparisons) of symptoms vs SARS-CoV-2-negative episodes. In this cohort study, during the first pandemic year when mostly partial or full in-person learning occurred, the SARS-CoV-2 incidence rate in children was substantially higher than estimated from routine testing or seroprevalence data and was similar to that of adult household members. Unlike in unvaccinated adults, SARS-CoV-2 symptoms and symptom severity in children were similar to other common respiratory illnesses. These findings may prove useful when developing pediatric COVID-19 vaccine recommendations.

Indoor Air Pollution and Respiratory Illness in Children from Rural India: A Pilot Study

Indoor air pollution measured in terms of particulate matter < 2.5 microm in diameter (PM2.5), is an important cause of respiratory illness in children. Therefore, PM2.5 levels in rural households and its correlation with respiratory illness-related symptoms in children were studied. A questionnaire-based survey of children for respiratory illness-related symptoms was conducted in 37 households of a village (Khanpurjupti, Delhi-NCR, India) from September 2011 to October 2011. Assessment of 24-hour PM2.5 level was done using University of California-Berkeley Particle and Temperature Sensor (UCB-PATS). Thirty-seven households in a rural area were studied. These were divided into 20 respiratory households, i.e. those with children with respiratory illness-related symptoms and 17 control households. The 24-hour PM2.5 was measured in all the houses. The average minimum and maximum PM2.5 levels were 7.24 mg/m3 and 22.70 mg/m3, respectively (mean = 10.47 mg/m3) among the 20 respiratory households. The average minimum and maximum PM2.5 levels were 1.10 mg/m3 and 18.17 mg/m3, respectively (mean = 4.99 mg/m3) in the 17 control households. The PM2.5 levels were significantly greater (p < 0.05) in houses where children had respiratory symptoms compared to the control households. Further, biomass fuel use and number of family members were significantly associated with respiratory illness in children. Increased PM2.5 levels, biomass fuel use and number of family members were found to be associated with increased occurrence of respiratory illness in children.

Commentary: Serum Calprotectin Is a Valid Biomarker in Distinction of Bacterial Urinary Tract Infection From Viral Respiratory Illness in Children Under 3 Years of Age.

Commentary: Serum Calprotectin Is a Valid Biomarker in Distinction of Bacterial Urinary Tract Infection From Viral Respiratory Illness in Children Under 3 Years of Age.