Tract Infections In Young Children Research Articles

Novel insights into the host cell glycan binding profile of human metapneumovirus.

Numerous viruses have been found to exploit glycoconjugates expressed on human cells as their initial attachment factor for viral entry and infection. The virus-cell glycointeractome, when characterized, may serve as a template for antiviral drug design. Heparan sulfate proteoglycans extensively decorate the human cell surface and were previously described as a primary receptor for human metapneumovirus (HMPV). After respiratory syncytial virus, HMPV is the second most prevalent respiratory pathogen causing respiratory tract infection in young children. To date, there is neither vaccine nor drug available to prevent or treat HMPV infection. Using a multidisciplinary approach, we report for the first time the glycointeractome of the HMPV fusion (F) protein, a viral surface glycoprotein that is essential for target-cell recognition, attachment, and entry. Our glycan microarray and surface plasmon resonance results suggest that Galβ1-3/4GlcNAc moieties that may be sialylated or fucosylated are readily recognized by HMPV F. The bound motifs are highly similar to the N-linked and O-linked glycans primarily expressed on the human lung epithelium. We demonstrate that the identified glycans have the potential to compete with the cellular receptors used for HMPV entry and consequently block HMPV infection. We found that lacto-N-neotetraose demonstrated the strongest HMPV binding inhibition in a cell infection assay. Our current findings offer an encouraging and novel avenue for the design of anti-HMPV drug candidates using oligosaccharide templates.IMPORTANCEAll cells are decorated with a dense coat of sugars that makes a sugar code. Many respiratory viruses exploit this sugar code by binding to these sugars to cause infection. Human metapneumovirus is a leading cause for acute respiratory tract infections. Despite its medical importance, there is no vaccine or antiviral drug available to prevent or treat human metapneumovirus infection. This study investigates how human metapneumovirus binds to sugars in order to more efficiently infect the human host. We found that human metapneumovirus binds to a diverse range of sugars and demonstrated that these sugars can ultimately block viral infection. Understanding how viruses can take advantage of the sugar code on our cells could identify new intervention and treatment strategies to combat viral disease.

The genomic evolutionary dynamics and global circulation patterns of respiratory syncytial virus

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in young children and the second leading cause of infant death worldwide. While global circulation has been extensively studied for respiratory viruses such as seasonal influenza, and more recently also in great detail for SARS-CoV-2, a lack of global multi-annual sampling of complete RSV genomes limits our understanding of RSV molecular epidemiology. Here, we capitalise on the genomic surveillance by the INFORM-RSV study and apply phylodynamic approaches to uncover how selection and neutral epidemiological processes shape RSV diversity. Using complete viral genome sequences, we show similar patterns of site-specific diversifying selection among RSVA and RSVB and recover the imprint of non-neutral epidemic processes on their genealogies. Using a phylogeographic approach, we provide evidence for air travel governing the global patterns of RSVA and RSVB spread, which results in a considerable degree of phylogenetic mixing across countries. Our findings highlight the potential of systematic global RSV genomic surveillance for transforming our understanding of global RSV spread.

Urinary Tract Infections in Children

Patient Education| 2021 Urinary Tract Infections in Young Children Connected Content Translation: Infecciones de las vías urinarias en niños pequeños: (Urinary Tract Infections in Young Children) Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Share Icon Share Facebook Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Urinary Tract Infections in Young Children. Pediatric Patient Education 2021; 10.1542/peo_document109 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All AAP SitesAll PublicationsPediatric Patient Education Search Advanced Search Topics: urinary tract, urinary tract infections, urine, urinary bladder, kidney, fever The urinary tract makes and stores urine. It is made up of the kidneys, ureters, bladder, and urethra (see illustration). The kidneys produce urine. Urine travels from the kidneys down 2 narrow tubes called the ureters to the bladder. The bladder is a thin muscular bag that stores urine until it is time to empty urine out of the body. When it is time to empty the bladder, a muscle at the bottom of the bladder relaxes. Urine then flows out of the body through a tube called the urethra. The opening of the urethra is at the end of the penis in boys and above the vaginal opening in girls. Normal urine has no germs (bacteria). However, bacteria can get into the urinary tract from 2 sources: (1) the skin around the rectum and genitals and (2) the... © 2010 American Academy of Pediatrics, Reaffirmed 01/2017. All rights reserved. You do not currently have access to this content.

Knockdown of the Autophagy Protein Beclin-1 Does Not Affect Innate Cytokine Production in Human Lung Epithelial Cells during Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in young children, globally. Autophagy is a cellular degradation process that mediates cell survival. Studies using mouse models have demonstrated that inhibiting autophagy affects the production of cytokines triggered by RSV. However, the effect of autophagy on RSV-induced cytokine production in human cells remains inadequately studied. Our previous research showed that inhibiting autophagy using pharmacological inhibitors did not affect the innate cytokine production in human lung epithelial cells (BEAS-2B) following RSV infection. In this study, we sought to validate these findings using a more specific approach, employing short-interfering RNA (siRNA) to target the important autophagy protein Beclin-1 (Bec-1). Prior to measuring cytokine production, we confirmed that silencing Bec-1 with siRNA effectively suppressed autophagy without affecting cell viability. Our results revealed that inhibiting autophagy through Bec-1 knockdown did not affect the production of innate cytokines CXCL8 and CCL5 in BEAS-2B cells during RSV infection, consistent with our previous findings using pharmacological inhibitors. Overall, our data suggest that targeting autophagy may not be an effective strategy for alleviating RSV-induced airway inflammation.

A Study of the Clinical Profile and Respiratory Index of Severity in Children (RISC) Score in Infants Admitted With Acute Respiratory Infections at a Tertiary Care Hospital.

Background Pneumonia is a major infectious cause of mortality in young children worldwide. The Respiratory Index of Severity in Children (RISC) score was designed with the intent to provide an objective mean to quantify the severity of lower respiratory tract infection in young children based on their risk of mortality. Knowledge about the clinical profile of acute respiratory infections and the scoring system predicting the risk of mortality helps in modifying treatment strategies. This study was undertaken at a resource-limited, tertiary-care public hospital in southern India with the objectives of describing the clinical profile of infants admitted with acute respiratory infections and determining the association of the RISC score with mortality. Method This was a retrospective observational study conducted over six months. Case records of infants admitted with acute respiratory infections were reviewed. The socio-demographic and clinical details of each case were recorded. The RISC score was calculated using clinical parameters which included the history of refusal of feeds, oxygen saturation lower than 90%, chest in-drawing, wheezing, and low weight-for-age. The maximum score was six. Descriptive data was represented using mean, standard deviation, and percentage or proportion. The association between any two categorical variables was analyzed using the chi-square test. The differences between any two continuous variables were analyzed using the independent sample t-test. A p-value of < 0.05 was considered statistically significant. Results A total of 75 infants were admitted with a diagnosis of acute respiratory infection during the study period. Of these, 68 were included in the study. The mean age of infants was 6.69 ± 3.96 months; 58.8% were male, 41 (60%) were exclusively breastfed, and 51 (75%) were up-to-date immunized. Twenty (29.4%) infants had a history of exposure to indoor smoke. The majority (67.6%) had pneumonia. Nine (13.2%) were mechanically ventilated. The mean duration of hospital stay was 8.16 ± 5.45 days. Sixty-three (92.64%) infants recovered and there were five deaths. The presence of less than 90% oxygen saturation (p-value=0.004), a diagnosis of severe pneumonia (p-value <0.001), and the need for mechanical ventilation (p-value <0.001) were significantly associated with mortality. A statistically significant (p-value=0.001) association was observed between the RISC score and mortality. Conclusions Addressable factors like the absence of exclusive breastfeeding, partial-immunization status, exposure to indoor smoke, and malnutrition were observed in infants with acute respiratory infections, which reinforces the importance of protective and preventive strategies for the control of pneumonia. The RISC score was observed to be beneficial in predicting mortality in an infant with acute respiratory infection. Triaging and early identification of infants at risk of mortality using this score could be very helpful in initiating timely treatment to reduce mortality, especially in resource-limited settings.

Extensive Multiple 2D-/3D-QSAR Modeling, Molecular Docking and Pharmacophoric Approaches for Piperazinylquinoline Derivatives as Respiratory Syncytial Virus Fusion Inhibitors.

The human respiratory syncytial virus (RSV) is responsible for causing upper and lower respiratory tract infections in young children. RSV Fusion (F) protein is a surface glycoprotein that facilitates virus entry into host cells. Thus, newer designing of RSV Fusion (F) protein inhibitors is required on an urgent basis. In the present study, we have developed statistically robust. Quantitative structure-activity relationship (QSAR) models for the effective designing of newer analogues of piperazinylquinoline derivatives (H1-H12). Our developed models were retained with high statistical parameters (R2 > 0.6 and Q2 > 0.5). Our developed pharmacophore, model (AADHRR_2) (indicating that two hydrogen bond acceptors, one hydrogen bond donor, one hydrophobic group, and two aromatic rings) is crucial for retaining the activities of piperazinylquinoline derivatives against RSV. Moreover, docking analysis of 12 new analogues on RSV pre-F in complex with 5C4 Fab (PDB ID: 5W23) and post-F trimeric protein (PDB ID: 3RRR) suggested higher affinities of these molecules against studied targets with good docking scores. Thus, one can implement developed QSAR models, docking analogy and Pharmacophore models for identifications of potent leads for designed molecules as RSV Fusion (F) protein inhibitors.

Evaluating the efficacy of corticosteroids and bronchodilators in the management of paediatric bronchiolitis

Background: Bronchiolitis, a standard lower tract infection in young children, poses significant challenges in terms of diagnosis and management. Corticosteroids and bronchodilators are often prescribed to manage this condition, despite limited evidence supporting their efficacy. This study aimed to judge the effectiveness of corticosteroids and bronchodilators within the management of paediatric bronchiolitis. Objective: to see the clinical efficacy of corticosteroids and bronchodilators in improving respiratory symptoms and reducing hospitalization rates among paediatric patients with bronchiolitis. Study Settings and Sample Size: This study was conducted at different centres including Department of Paediatrics, Social Security MNCH Hospital, Dera Ghazi Khan, Punjab and Sahara Medical College Narowal, Punjab in the period from October, 2022 to March, 2023 enrolling 300 children aged 1 month to 2 years with a clinical diagnosis of bronchiolitis. Methods: Participants were randomly assigned to at least one of three treatment groups: corticosteroids (n=100), bronchodilators (n=100), or placebo (n=100). the first outcome was improvement within the Respiratory Distress Assessment Instrument (RDAI) score. Secondary outcomes included hospitalization rates, length of hospital stay, and adverse events. Results: Children within the corticosteroid group experienced a significantly greater improvement in RDAI scores compared to the placebo group (p&lt;0.001).

Respiratory syncytial virus infection and novel interventions.

The large global burden of respiratory syncytial virus (RSV) respiratory tract infections in young children and older adults has gained increased recognition in recent years. Recent discoveries regarding the neutralization-specific viral epitopes of the pre-fusion RSV glycoprotein have led to a shift from empirical to structure-based design of RSV therapeutics, and controlled human infection model studies have provided early-stage proof of concept for novel RSV monoclonal antibodies, vaccines and antiviral drugs. The world's first vaccines and first monoclonal antibody to prevent RSV among older adults and all infants, respectively, have recently been approved. Large-scale introduction of RSV prophylactics emphasizes the need for active surveillance to understand the global impact of these interventions over time and to timely identify viral mutants that are able to escape novel prophylactics. In this Review, we provide an overview of RSV interventions in clinical development, highlighting global disease burden, seasonality, pathogenesis, and host and viral factors related to RSV immunity.

Antimicrobial resistance of breakthrough urinary tract infections in young children receiving continual antibiotic prophylaxis.

Continual antibiotic prophylaxis (CAP) can reduce the risk of recurrent UTI (rUTI). However, antimicrobial resistance in subsequent UTIs is a concern. This study aimed to explore antimicrobial resistance in young children prescribed CAP for rUTIs. A retrospective review of patient records/microbiology results was undertaken for children < 2years of age, on CAP, with 2-3 clean catch/mid-stream/supra-pubic aspirate urine cultures with a pure growth of bacteria, between January 2017 and December 2019. One hundred twenty-four urine specimens from 54 patients (26 (48%) males, median age 6months) were analysed. CAP prescribed was trimethoprim in 37 (69%), cefalexin in 11 (29%), and nitrofurantoin in 6 (11%). Based on antimicrobial susceptibility of the index UTI within the study period, 41 patients (76%) grew organisms on urine culture classified as sensitive and 13 (24%) resistant. Thirty-five (65%) children had congenital anomaly of the kidneys and urinary tract (CAKUT); they were more likely to be in the resistant group (P = 0.032). Escherichia coli (37/54, 69%) was the commonest index uropathogen. The resistant group had a higher proportion of non-E. coli index UTI pathogens (P = 0.098). Breakthrough UTI with a CAP-resistant organism was more likely in the resistant group (P = 0.010). Age, sex, and kidney scarring on DMSA (dimercaptosuccinic acid) scan were not significantly different between groups. Conclusion: Over a 3-year period, the proportion of children on CAP with resistant organism UTI doubled and resistant infections were more likely in children with CAKUT. Development of non-antimicrobial prophylaxis options is required. What is Known: • Recurrent urinary tract infections are common in children, particularly in those with underlying anatomical abnormalities of the kidneys and urinary tract. •Continuous antibiotic prophylaxis is used frequently in these children, however there is a lack of consensus on whether the potential benefits of CAP outweigh the harms. What is New: • This study adds further evidence towards the consequences of using continuous antibiotic prophylaxis in recurrent UTI; specifically, a 2-fold increase in antimicrobial resistance was seen in subsequent UTIs following long-term use of CAP, providing further vigour for the need for non-antibiotic alternatives.

Evaluation of Clinical Case Definitions for Respiratory Syncytial Virus Lower Respiratory Tract Infection in Young Children.

Various case definitions of respiratory syncytial virus lower respiratory tract infection (RSV-LRTI) are currently proposed. We assessed the performance of 3 clinical case definitions against the World Health Organization definition recommended in 2015 (WHO 2015). In this prospective cohort study conducted in 8 countries, 2401 children were followed up for 2 years from birth. Suspected LRTIs were detected via active and passive surveillance, followed by in-person clinical evaluation including single timepoint respiratory rate and oxygen saturation (by pulse oximetry) assessment, and nasopharyngeal sampling for RSV testing by polymerase chain reaction. Agreement between case definitions was evaluated using Cohen's κ statistics. Of 1652 suspected LRTIs, 227 met the WHO 2015 criteria for RSV-LRTI; 73 were classified as severe. All alternative definitions were highly concordant with the WHO 2015 definition for RSV-LRTI (κ: 0.95-1.00), but less concordant for severe RSV-LRTI (κ: 0.47-0.82). Tachypnea was present for 196/226 (86.7%) WHO 2015 RSV-LRTIs and 168/243 (69.1%) LRTI/bronchiolitis/pneumonia cases, clinically diagnosed by nonstudy physicians. Low oxygen saturation levels were observed in only 55/226 (24.3%) WHO 2015 RSV-LRTIs. Three case definitions for RSV-LRTI showed high concordance with the WHO 2015 definition, while agreement was lower for severe RSV-LRTI. In contrast to increased respiratory rate, low oxygen saturation was not a consistent finding in RSV-LRTIs and severe RSV-LRTIs. This study demonstrates that current definitions are highly concordant for RSV-LRTIs, but a standard definition is still needed for severe RSV-LRTI. NCT01995175.

Incidence, hospitalization, and mortality in children aged 5 years and younger with respiratory syncytial virus-related diseases: A systematic review and meta-analysis.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in young children. We aimed to analyze the factors affecting the estimation of RSV-related disease burden, and to provide evidence to help establish a surveillance system. We searched the English- and Chinese-language databases for articles published between January 1, 2010 and June 2, 2022. The quality of the included articles was assessed using the Agency for Healthcare Research and Quality scale. Random-effects models were used for data synthesis and subgroup analyses. This review was registered in the Prospective Register of Systematic Reviews (PROSPERO: CRD42022372972). We included 44 studies (149,321,171 participants), all of which were of medium or high quality. The pooled RSV-related disease incidence, hospitalization rate, in-hospital mortality, and overall mortality rates in children aged 5 years and younger were 9.0 per 100 children per year (95% confidence interval [CI]: 7.0-11.0), 1.7 per 100 children per year (95% CI: 1.3-2.1), 0.5 per 100 children per year (95% CI: 0.4-0.5), and 0.05 per 100 children per year (95% CI: 0.04-0.06), respectively. Age, economics, surveillance types, case definition, and data source were all recognized as influencing factors. A standardized and unified RSV surveillance system is required. Case definition and surveillance types should be fully considered for surveillance of different age groups.

Urine specific gravity, pyuria, and neutrophil gelatinase-associated lipocalin for identifying urinary tract infection in young children.

To determine whether urine neutrophil gelatinase-associated lipocalin (uNGAL) might be superior to pyuria for detecting urinary tract infection (UTI) regardless of urine specific gravity (SG) in young children. We conducted a retrospective analysis of children aged < 3 years who were evaluated for UTI with urinalysis, urine culture, and uNGAL measurements during a 5-year period. Sensitivity, specificity, likelihood ratios (LRs), predictive values (PVs), area under the curves (AUCs) of uNGAL cut-off levels, and various microscopic pyuria thresholds for detecting UTI were calculated for dilute (SG < 1.015) and concentrated urine (SG ≥ 1.015). Of 456 children included, 218 had UTI. The diagnostic value of urine white blood cell (WBC) concentration to define UTI changed with urine SG. For detecting UTI, uNGAL cut-off of 68.4 ng/mL had higher AUC values than pyuria ≥ 5 WBCs/high power field (HPF) for dilute and concentrated urine samples (both P < 0.05). Positive LR and PV and specificity of uNGAL were all greater than those of pyuria ≥ 5 WBCs/HPF regardless of urine SG, although the sensitivity of pyuria ≥ 5 WBCs/HPF was higher than that of uNGAL cut-off for dilute urine (93.8% vs. 83.5%) (P < 0.05). At uNGAL ≥ 68.4 ng/mL and ≥ 5 WBCs/HPF, posttest probabilities of UTI were 68.8% and 57.5% for dilute urine and 73.4% and 57.3% for concentrated urine, respectively. Urine SG can affect the diagnostic performance of pyuria for detecting UTI and uNGAL might be helpful for identifying UTI regardless of urine SG in young children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Comparative evaluation of high flow oxygen therapy versus low flow oxygen therapy in the management of acute moderate bronchiolitis

Background: Acute bronchiolitis is the most common respiratory tract infection in young children. Despite the high prevalence, no consensus exists on management. Hence the present study was conducted to find out the efficacy of high flow oxygen therapy (HFNC) versus low flow oxygen therapy in the management of acute moderate bronchiolitis. Methods: Prospective randomized controlled study of 100 children aged between 2 months to 24 months with signs and symptoms of acute moderate bronchiolitis were admitted to Indira Gandhi Institute of Child Health, Bangalore from January 2018 to June 2019 formed the study group, they were randomised into 2 groups, group A received high flow oxygen therapy and group B received low flow oxygen therapy. Results: Out of 100 children enrolled in the study, 50 children (group A) received high flow oxygen therapy and 50 children (group B) received low flow oxygen therapy. At 24 hours the mean severity score for group A was 0.46±077 and group B was 1.86±0.86 (p&lt;0.001). Maximum improvement in O2 saturation was observed in group A compared to group B. The duration of hospital stay was shorter (2-3 days) in group A with a mean of 2.20 days and was longer (4-5 days) in group B with a mean value of 3.84 days which was statistically significant (p&lt;0.001). Conclusions: Children with acute bronchiolitis treated with heated humidified high flow oxygen (HFNC) had early improvement in the clinical severity score, reduced duration of oxygen requirement and decrease in the length of hospital stay. Hence heated humidified high flow oxygen (HFNC) is an effective and safe modality of treatment for children with acute moderate bronchiolitis compared to low flow oxygen therapy (p&lt;0.0001).

Influence of Sex on Respiratory Syncytial Virus Genotype Infection Frequency and Nasopharyngeal Microbiome.

Respiratory syncytial virus (RSV) has a significant health burden in children, older adults, and the immunocompromised. However, limited effort has been made to identify emergence of new RSV genotypes' frequency of infection and how the combination of nasopharyngeal microbiome and viral genotypes impact RSV disease outcomes. In an observational cohort designed to capture the first infant RSV infection, we employed multi-omics approaches to sequence 349 RSV complete genomes and matched nasopharyngeal microbiomes, during which the 2012/2013 season was dominated by RSV-A, whereas 2013 and 2014 was dominated by RSV-B. We found non-G-72nt-duplicated RSV-A strains were more frequent in male infants (P = 0.02), whereas G-72nt-duplicated genotypes (which is ON1 lineage) were seen equally in both males and females. DESeq2 testing of the nasal microbiome showed Haemophilus was significantly more abundant in infants with RSV-A infection compared to infants with RSV-B infection (adjusted P = 0.002). In addition, the broad microbial clustering of the abundant genera was significantly associated with infant sex (P = 0.03). Overall, we show sex differences in infection by RSV genotype and host nasopharyngeal microbiome, suggesting an interaction between host genetics, virus genotype, and associated nasopharyngeal microbiome. IMPORTANCE Respiratory syncytial virus (RSV) is one of the leading causes of lower respiratory tract infections in young children and is responsible for high hospitalization rates and morbidity in infants and the elderly. To understand how the emergence of RSV viral genotypes and viral-respiratory microbiome interactions contribute to infection frequency and severity, we utilized an observational cohort designed to capture the first infant RSV infection we employed multi-omics approaches to sequence 349 RSV complete genomes and matched nasopharyngeal microbiomes. We found non-G-72nt-duplicated RSV-A genotypes were more frequent in male infants, whereas G-72nt-duplicated RSV-A strains (ON1 lineage) were seen equally in both males and females. Microbiome analysis show Haemophilus was significantly more abundant in infants with RSV-A compared to infants with RSV-B infection and the microbial clustering of the abundant genera was associated with infant sex. Overall, we show sex differences in RSV genotype-nasopharyngeal microbiome, suggesting an interaction host genetics-virus-microbiome interaction.

An outbreak of upper respiratory tract infections in young children during the COVID-19 pandemic: a lesson from Hong Kong

An outbreak of upper respiratory tract infections in young children during the COVID-19 pandemic: a lesson from Hong Kong

Severe Human Rhinovirus Lower Respiratory Tract Infections in Young Children

Severe Human Rhinovirus Lower Respiratory Tract Infections in Young Children

Profiles and predictive value of cytokines in children with human metapneumovirus pneumonia.

Human metapneumovirus (HMPV) is an important cause of respiratory tract infections in young children. Early innate immune response to HMPV is focused on induction of antiviral interferons (IFNs) and other pro-inflammatory cytokines that are critical for the formation of adaptive immune responses. To evaluate the predictive value of Th1/Th2 cytokines which include IL-2, IL-4, IL-6, IL-10, INF-γ and TNF-α in pneumonia caused by HMPV. A retrospective study was performed among 59 pneumonia pediatric patients with HMPV infection and 33 healthy children as the control cohort, which was detected by the immunofluorescence assay, and the Th1/Th2 cytokines were measured by flow cytometry. 131 children infected with Influenza virus A (IVA) and 41 children infected with influenza virus B (IVB) were detected by RT-PCR assay in throat swabs. When compared with the healthy children, children who were infected with HMPV pneumonia had a significantly lower level of IL-2 (p < 0.001) and higher levels of IL-4 (p < 0.001), IL-6 (p = 0.001), IL-10 (p < 0.001), and IFN-γ (p < 0.001). Compared with patients diagnosed with IVA or IVB infection, HMPV-positive patients had significantly higher levels of IL-4 (p < 0.001 and < 0.001), IFN-γ (p < 0.001 and < 0.001), and TNF-α (p < 0.001 and 0.016). Moreover, compared with IVA patients, HMPV-positive patients had a significantly lower level of IL-6 (p = 0.033). Finally, when comparing cytokine levels among the patients with HMPV pneumonia, IL-6 and TNF-α levels were found to be significantly higher in the severe group than the mild group (p = 0.027 and 0.049). The IL-6 and TNF-α were used to differentiate between mild symptoms and severe symptoms in children diagnosed with HMPV pneumonia with an AUC of 0.678 (95% CI 0.526-0.829) and 0.658 (95% CI 0.506-0.809), respectively. Our study indicated that difference in cytokine trends depending on the virus species. The levels of IL-4, TNF-α and IFN-γ were significantly distinguished in children infected with HMPV versus IVA and IVB. IL-6 and TNF-α may be helpful in assessing the severity and prognosis of HMPV infection.

Clinical characteristics and molecular epidemiology of human metapneumovirus in children with acute lower respiratory tract infections in China, 2017 to 2019: A multicentre prospective observational study.

Human metapneumovirus (HMPV) infection is one of the leading causes of hospitalization in young children with acute respiratory illness. In this study, we prospectively collected respiratory tract samples from children who were hospitalized with acute lower respiratory tract infection in six hospitals in China from 2017 to 2019. HMPV was detected in 145 out of 2733 samples (5.3%) from the hospitalized children. The majority of HMPV-positive children were under the age of two (67.6%), with a median age of one year. HMPV can independently cause acute lower respiratory tract infection in young children, while all patients showed mild clinical symptoms. Of all the co-infected patients, HMPV was most commonly detected with enterovirus (EV) or rhinovirus (RhV) (38.0%, followed by respiratory syncytial virus (RSV) (32.0%). The highest detection rate occurred from March to May in both northern and southern China. Out of 145 HMPV positive samples, 48 were successfully typed, of which 36 strains were subgrouped into subtypes A2c (75%), eight strains were included in subtype B1 (16.7%), and four strains were included in subtype B2 (8.3%). Moreover, 16 A2c strains contained 111-nucleotide duplications in the G gene. Twenty-seven complete HMPV genomes were successfully obtained, and 25 (92.6%) strains belonged to subtype A2c, whereas one strain was included in subgroup B1 and another was included in subgroup B2. A total of 277 mutations were observed in the complete genomes of 25 A2c strains. All results presented here improve our understanding of clinical characteristics and molecular epidemiology of HMPV infection in children.

How did the covid-19 pandemic affect lower respiratory tract infections in young children in England?

Abstract Background Social distancing policies to reduce transmission of covid-19 also reduced children's exposures to endemic respiratory viruses. We aimed to examine the impact of the covid-19 pandemic on lower respiratory tract infections in under 5s presenting to primary care in England. Methods Longitudinal trends analysis using electronic health records from a nationally representative primary care database. Our target population was children aged &amp;lt;5 years registered with a primary care practice from January 2015 to March 2021. Our main outcome was total weekly contacts with primary care for a lower respiratory tract infection (LRTI). We defined three pandemic phases from March 2020 - March 2021: i) first national lockdown (late March to early June 2020), ii) childcare settings reopened and second national lockdown with schools open (mid-June to mid-December 2020) and iii) third national lockdown with schools closed (late December 2020 to end of March 2021). We compared outcomes during each of the three phases with corresponding calendar weeks during pre-pandemic years 2015 to 2019. Results Our study population included 843 020 children &amp;lt;5 years who had 1 076 181 contacts with primary care for LRTIs. During the first phase (first lockdown) there were falls of 79.3% (95% CI: 73.6 to 84.5) from an average of 28 547 primary care contacts for LRTI in 2015 - 2019 to 5915 in 2020; there was a 78.9% (95% CI: 73.7 to 83.9) fall in phase two (childcare settings reopened and second lockdown) from 107 873 to 22 792 contacts; and a 77.7% (95% CI: 73.5 to 81.4) fall in phase three (third lockdown) from 57 200 to 12 764 contacts. Conclusions Children under 5 in England had fewer contacts with primary care for LRTIs during the covid-19 pandemic. This change likely reflects lower prevalence of respiratory illness due to fewer social contacts. This may impact on future health service use as these children have had less exposure, and therefore may have less immunity, to respiratory diseases. Key messages • Children under 5 had fewer contacts with primary care for lower respiratory tract infections during the covid-19 pandemic in England likely due to the restrictions in place to reduce social contacts. • The falls in lower respiratory tract infections during the covid-19 pandemic in under 5s may mean they have less immunity to respiratory viruses which may impact upon their future health service use.

A Candidate Therapeutic Monoclonal Antibody Inhibits Both HRSV and HMPV Replication in Mice.

Human metapneumovirus (HMPV) and human respiratory virus (HRSV) are two leading causes of acute respiratory tract infection in young children. While there is no licensed drug against HMPV, the monoclonal antibody (mAb) Palivizumab is approved against HRSV for prophylaxis use only. Novel therapeutics against both viruses are therefore needed. Here, we describe the identification of human mAbs targeting these viruses by using flow cytometry-based cell sorting. One hundred and two antibodies were initially identified from flow cytometry-based cell sorting as binding to the fusion protein from HRSV, HMPV or both. Of those, 95 were successfully produced in plants, purified and characterized for binding activity by ELISA and neutralization assays as well as by inhibition of virus replication in mice. Twenty-two highly reactive mAbs targeting either HRSV or HMPV were isolated. Of these, three mAbs inhibited replication in vivo of a single virus while one mAb could reduce both HRSV and HMPV titers in the lung. Overall, this study identifies several human mAbs with virus-specific therapeutic potential and a unique mAb with inhibitory activities against both HRSV and HMPV.