BackgroundThe mechanisms underlying refractory Mycoplasma pneumoniae (M. pneumoniae) pneumonia (RMPP) and its association with adaptive immune dysfunction remain incompletely defined. This study investigated clinical features and peripheral lymphocyte profiles in children with RMPP versus those with common M. pneumoniae pneumonia (CMPP) to identify immune disturbances that may serve as early predictive indicators.MethodsOf 622 children diagnosed with M. pneumoniae pneumonia between January 2019 and January 2024, 139 with single infection were enrolled: 72 RMPP and 67 CMPP. Clinical data and laboratory inflammatory markers were collected. Peripheral lymphocyte subsets (percentages and absolute counts) were determined by flow cytometry. Independent risk factors for RMPP were identified using multivariate logistic regression. A combined diagnostic model was constructed and evaluated by area under the receiver operating characteristic curve.ResultsChildren with RMPP exhibited more severe clinical manifestations than those with CMPP, including prolonged high fever, higher rates of severe disease and glucocorticoid use, and extensive lung involvement (multilobar infiltration, pleural effusion). Laboratory tests revealed an accentuated systemic inflammatory response (elevated C-reactive protein, procalcitonin) in RMPP. Immunologically, RMPP was characterized by extensive reductions in absolute lymphocyte counts—encompassing T cells (particularly helper and naïve subsets), B cells, regulatory T cells, and γδ T cells—despite minimal percentage differences in most subsets. Percentage-wise, RMPP showed decreased helper T cells but increased proportions of helper effector memory T cells, terminally differentiated effector memory helper/cytotoxic T cells re-expressing CD45RA. Multivariate analysis identified older age, longer fever duration, pleural effusion, and decreased absolute plasmablast count as independent predictors of RMPP. A four-indicator combined model demonstrated good discrimination (area under the curve, 0.81; 95% confidence interval, 0.74–0.88); an optimal threshold of 0.48 yielded 96% sensitivity and 52% specificity.ConclusionRMPP involves profound adaptive immunosuppression, marked by widespread reduction in total lymphocytes and key functional subsets—particularly plasmablasts—alongside an exhausted/memory phenotypic shift in specific T cells. Plasmablast reduction represents a novel immunological marker for predicting RMPP. A model integrating plasmablast count, age, fever duration, and pleural effusion holds promise for early RMPP identification, providing valuable insights into its immunopathogenesis and informing early warning strategies.

BackgroundHuman adenovirus (HAdV) is a significant cause of severe pneumonia in children that often causes sequelae. Although immune disorders are known to be associated with disease progression, comprehensive immunological predictors have not been identified. The purpose of this study was to explore the ability of multiple immunological indicators to predict severe adenovirus pneumonia (SAP) and to develop an immune-based nomogram for the early prediction of SAP in children.MethodsThis study involved a retrospective analysis of children with adenovirus pneumonia who were hospitalized and received treatment at the Department of Respiratory Medicine, Capital Center for Children's Health, Capital Medical University between January 2017 and June 2025. Patients were stratified into mild and severe groups on the basis of clinical manifestations. They were subsequently randomly allocated at an 80:20 ratio into a training set and a cross-validation set for nomogram development and validation. R software (version 4.4.3) was used for statistical analysis, and effect sizes are expressed as odds ratios (ORs) and 95% confidence intervals (CIs).ResultsAmong the 1220 cases included, 357 (29.3%) were classified as severe. In both the training and cross-validation sets, patients with SAP were younger and had longer hospital stays (all P < 0.001). After the adjustments for age and sex, logistic regression in the training set revealed seven significant factors associated with SAP occurrence in children: Mycoplasma pneumoniae infection (OR = 1.372, 95% CI: 1.04–1.809, P < 0.001); complement component 3 (C3) (OR = 0.234, 95% CI: 0.132–0.417, P < 0.001) and 4 (C4) (OR = 0.075, 95% CI: 0.018–0.31, P < 0.001); immunoglobulin G (IgG) (OR = 1.049, 95% CI: 1.028–1.071, P < 0.001); and the percentages of CD3+ [CD3+ (%)] (OR = 0.965, 95% CI: 0.952–0.979, P < 0.001), CD4+ [CD4+ (%)] (OR = 0.950, 95% CI: 0.934–0.967, P < 0.001), and CD19+ cells [CD19+ (%)] (OR = 1.042, 95% CI: 1.028–1.057, P < 0.001). Furthermore, logistic regression of the validation set revealed C3, C4, IgG, CD3+(%), CD4+ (%) and CD19+(%) as consistent predictors of SAP across datasets. Incorporating the significant factors improved model discrimination, increasing the area under the curve (AUC) from 0.627 to 0.836 in the training set and from 0.678 to 0.913 in the cross-validation set. The final nomogram model based on the significant factors demonstrated strong calibration and discrimination (C-index: 0.731 in the training set, 0.812 in the cross-validation set), supporting its potential for clinical risk stratification.ConclusionThis study identified and validated seven independent factors significantly associated with SAP in children. A nomogram incorporating these factors was developed and it demonstrated favourable discriminative performance and good calibration. The model exhibited high sensitivity and maintained high predictive accuracy across both datasets, indicating its potential clinical utility for individualized risk stratification.

ImportanceMycoplasma pneumoniae pneumonia (MPP) with chest computed tomography (CT) findings showing airway involvement as the main manifestation has begun to be noted and increasingly reported. This type of MPP has different clinical features and may progress to bronchiolitis obliterans (BO). Early recognition and treatment are helpful for reducing sequelae.ObjectiveTo investigate the clinical characteristics of MPP patients with airway involvement and provide guidance for clinical recognition of this type.MethodsData from children diagnosed with MPP were collected. Forty-one patients were assigned to the airway group according to chest CT, and 114 patients were assigned to the air space group. The clinical data of the two groups were compared and analyzed.ResultsThe children in the airway group were younger, and the prevalence of wheezing, pulmonary moist rales, and allergic background in the airway group was greater. The prevalence of severe MPP, the proportions of neutrophils, C-reactive protein, and D-dimer were lower in the airway group than in the air space group. Significantly more patients had lung involvement in both airways in the airway group. No cases of BO were found in the airway group.InterpretationMycoplasma pneumoniae-associated airway involvement mostly occurs in young children, especially in atopic individuals. Patients with this type of pneumonia are prone to have clinical wheezing and pulmonary moist rales. The airway group included relatively few severe cases, but more patients had involvement of both lungs. Whether the patients in the airway group had a greater chance of developing BO needs further investigation.

The underdevelopment of microbiological tests has contributed to diagnostic delay and inappropriate use of antibiotics in patients with lower respiratory tract infections, which is ranked as the seventh leading cause of death globally. Next-generation sequencing (NGS) has emerged as a promising platform for the diagnosis of infectious diseases, albeit with high costs and challenges in result interpretation. Here we evaluated two NGS-based pathogen detection assays for the etiological diagnosis of pneumonia in a prospective cohort of 257 patients. Both assays utilized multiplex polymerase chain reaction (PCR) for pathogen enrichment. One assay was designed to promiscuously amplify and identify more than 1,000 pathogens (broad-spectrum targeted next-generation sequencing [bs-tNGS]), while the other specifically targeted 194 pathogens (pathogen-specific targeted next-generation sequencing [ps-tNGS]). The analytical and diagnostic performances of both assays were compared using a composite clinical reference standard. The specificity of ps-tNGS was higher than that of bs-tNGS (84.85% vs. 75.00%), while the sensitivities of both assays were similar (>89%). In addition, a significant overlap in the frequently detected pathogens by the two methods was observed. Moreover, the enrichment of pathogens via multiplex PCR for ps-tNGS has alleviated the requirement for deep sequencing in the shotgun metagenomic workflows and thus dramatically lowered the assay cost. This study demonstrated that ps-tNGS achieved a better overall diagnostic performance and may potentially replace bs-tNGS in the clinical application.IMPORTANCEMicrobial enrichment in metagenomic next-generation sequencing has been achieved through differential cell lysis, but the results varied, depending on experimental procedures and sample types. Therefore, direct enrichment of pathogen DNA/RNA was attempted via multiplex PCR or hybrid probe capture (targeted next-generation sequencing [tNGS]). We evaluated two enrichment methods based on multiplex PCR. One method utilized a primer design strategy to amplify over 1,000 respiratory pathogens (bs-tNGS), while the other specifically targeted 194 pathogens (ps-tNGS). Our findings disavowed the notion that "the more, the better" in tNGS workflows, since ps-tNGS exhibited equivalent sensitivity and, notably, higher specificity than bs-tNGS in a prospective cohort of 257 patients who were suspected of having pneumonia. In future evaluations of tNGS assays, researchers should pay more attention to diagnostic specificity, rather than focusing solely on sensitivity, since a low specificity may potentially lead to misdiagnosis and overuse of antibiotics in cases of non-infectious diseases.

ABSTRACT Importance Although macrolides combined with glucocorticoid therapy have demonstrated efficacy in preventing long‐term pulmonary lesions of severe Mycoplasma pneumoniae pneumonia (MPP), evidence regarding glucocorticoid dose is lacking. Objective To evaluate the effects of low‐ and high‐dose methylprednisolone on the risk of long‐term pulmonary lesions for children with severe MPP when combined with azithromycin. Methods This randomized, parallel‐controlled, multicenter clinical trial was conducted in mainland China and enrolled pediatric patients hospitalized with severe MPP. A total of 424 enrolled patients were randomized (allocation ratio of 1:1) to azithromycin combined with either a low‐dose [2 mg/(kg·d)] or a high‐dose [10 mg/(kg·d)] methylprednisolone treatment for 3 d followed by tapering over 12 d. The primary outcome was the incidence of composite adverse outcomes, including atelectasis, bronchiectasis, or bronchiolitis obliterans 6 months after treatment. Results A total of 118 (27.8%) developed adverse pulmonary lesions at 6 months after treatment; 66 of 211 (31.3%) in the high‐dose methylprednisolone group and 52 of 213 (24.4%) in the low‐dose group, respectively. The risk ratio of long‐term pulmonary lesions in a high‐dose group to those in a low‐dose group was 1.28 (95% confidence interval [95% CI]: 0.94–1.75). In addition, the risk of hypertension in the high‐dose group (8.1%, 17 of 211) was higher than that in the low‐dose group (1.4%, three of 213), with a risk ratio of 5.72 (95% CI: 1.70–19.23) Interpretation Azithromycin combined with low‐dose methylprednisolone demonstrates non‐inferior efficacy in reducing pulmonary lesions at 6‐month follow‐up compared to combined with high‐dose methylprednisolone while exhibiting a more favorable safety profile.

BACKGROUND:After a prolonged period of low detection rates, Mycoplasma pneumoniae resurged in China, during September to November, 2023, raising global concern. This study aims to gain a better understanding of the genetic mechanisms underlying the 2023 increase in cases and the evolutionary dynamics of the epidemic populations, which has been previously hampered due to limited genomic data of this pathogen. METHODS:We sequenced 685 M pneumoniae isolates, including 248 isolates from 11 Chinese provinces and municipalities in 2023 and 437 isolates from Beijing (2013-22). By analysing these isolates and 436 publicly global sequences, we reconstructed the pathogen's evolutionary history using time-calibrated phylogenies and effective population size inference. We investigated potential genomic variations contributing to the 2023 resurgence through genome-wide association study and conducted phylogeographic analysis of the 2023 isolates across China. FINDINGS:Two macrolide-resistant epidemic clusters (T1-2-EC1 and T2-2-EC2) were responsible for the 2023 resurgence in China. Both clusters, having acquired the 23S ribosomal RNA A2063G mutation conferring macrolide resistance, emerged in approximately 1997 and 2014, respectively, and subsequently outcompeted their predecessor populations. This coincided with China's large-scale adoption of azithromycin for paediatric community-acquired pneumonia around the early 2000s. Aside from macrolide resistance, T1-2-EC1 independently acquired 17 clade-specific mutations and T2-2-EC2 four clade-specific mutations, which could further explain their increased competitiveness. Whole-genome analysis revealed no resurgence-specific mutations in the 2023 isolates. Phylogeographic analysis showed rapid mixing of T1-2-EC1 isolates between different sampled regions within China. INTERPRETATION:Our study provides evidence that the 2023 resurgence in China is a continuation of the pre-COVID epidemic, rather than emergence of novel variants. The high prevalence of macrolide resistance and rapid intranational spread emphasise the urgent need for enhanced global surveillance of this pathogen. FUNDING:National Key Research and Development Program of China, National Natural Science Foundation of China for Key Programs of China Grants, and Beijing High-Level Public Health Technical Talent Project.

BackgroundThe pathogenic distribution of co-infections and immunological status of patients infected with human adenovirus serotypes 3 or 7 (HAdV-3 or HAdV-7) were poorly understood.MethodsThis study involved a retrospective analysis of respiratory specimens collected from enrolled children with lower respiratory tract infections (LRTIs), positive for HAdV-3 or HAdV-7 from January 2017 to December 2019. Demographic data, clinical features, laboratory and radiographic findings were compared to delineate the impact of co-infections, and immune responses on clinical severity of HAdV-3 or HAdV-7 infections.ResultsAmong 1311cases enrolled, there were 66 infected with HAdV-3 and 58 with HAdV-7. HAdV-7-infected patients exhibited more prolonged fever (100% vs 89.4%, p=0.014), pneumonia (100% vs 89.4%, p=0.014), hypoxia (34.5% vs 12.1%, p=0.003), higher propensity for aspartate aminotransferase exceeding 80U/L (21.1% vs 4.7%, p=0.006), D-Dimer exceeding 1.65mg/L (64.9% vs 12.5%, p<0.001), consolidation (50.0% vs 27.4%, p=0.011), and pleural effusion (32.8% vs 6.5%, p<0.001), co-infections with Mycoplasma pneumoniae (77.1% vs 32.6%, p<0.001), and multiple infections (56.8% vs 41.3%, p=0.007), compared to those with HAdV-3 infections. Immune cell analysis indicated that HAdV-7 infections led to a more pronounced decrease in CD3+ T cells (1596.8 vs 2444.8 cells/𝛍l, p=0.042), CD8+ cytotoxic T cells (668.6 vs 774.0 cells/µl, p=0.045), and increased NK cell percentages (11.5% vs 9.0%, p=0.044) compared to HAdV-3 infections.ConclusionsHospitalized children with HAdV-7-associated LRTIs exhibit greater severity, multiple infections, and significant potential for greater cellular immune dysregulation compared to those with HAdV-3 infection, indicating a more severe clinical course and distinct pathogenic profiles.

With the cancellation of non-pharmaceutical interventions (NPIs) since December 26, 2022, in Beijing, it is essential to update the endemic pattern of respiratory syncytial virus (RSV) in pediatric patients. Respiratory specimens were collected from hospitalized children with acute respiratory infections (ARIs) from January 2022 to December 2023 in Beijing for multiple pathogen screening. Then, specimens positive for RSV were subtyped by PCR and genotyped by G gene sequencing and phylogenetic analysis with Mega X. The clinical data of children only positive for RSV were compared using SPSS 22.0 software. Among 7131 specimens enrolled, there were 9.21% (203/2205) and 10.74% (529/4926) positive for RSV before and after the cancellation of NPIs, respectively. The expected RSV endemic season from November 2022 to March 2023 disappeared, and the RSV positive rates kept in 0.00% in January and February 2023, which were then increased rapidly to 14.81% in April and 24.60% in May, and to 14.35% and 18.18% again in November and December 2023, with the dominant subtype of RSV transferred from A to B in November 2023. Phylogenetic analysis revealed that clusters ON1.2 and BA9.3, especially, a new variant RSV-B-BA9-954bp, only showed in specimens collected after the cancellation of NPIs. Higher proportion of children aged 3-6 years and over 6 years which increased from 10.56% to 21.41%, and from 3.33% to 7.59%, respectively, and less severe pneumonia cases which decreased from 50.00% to 17.86%, were observed after the cancellation of NPIs. With the cancellation of NPIs, a delayed endemic season of RSV was shown in April and May 2023, with new clusters of ON1.2 and BA9.3, especially a new variant (RSV-B-BA9-954bp), a high proportion of children aged 3-6 years and over 6 years, and less severe pneumonia cases.

The pharmacokinetic profile of linezolid still needs further definition, and insufficient or excessive exposure may lead to treatment failure or development of adverse events. Our study aimed to establish a population pharmacokinetic (PPK) model for linezolid in children with bacterial infections, develop an optimal dosage, and evaluate its efficacy and safety. A total of 157 plasma samples from 80 patients were utilized in PPK modeling. A one-compartment model with first-order elimination was most suitable for describing the PK characteristics of linezolid. Weight and creatinine clearance were the significant covariates for clearance. The outcomes of Monte Carlo revealed that in children under 12 years, the probability of target attainment (PTA) for standard dosage (10 mg/kg q8h) was over 90.0% when minimum inhibitory concentration (MIC) ≤2 µg/mL, with a mere 1.4% probability of surpassing the safety threshold. Meanwhile, in children aged 12 years and above, the PTA for standard dosage (600 mg q12h) was over 83.0%, and the probability of surpassing the safety threshold was 0.0%. To take the results one step further, a total of 67 patients (using standard dosage) were enrolled in the efficacy and safety analysis. Of the patients, 95.5% were cured or improved clinical treatment outcomes, and 22.4% of the patients developed possible adverse events (AEs), and no patient experienced early discontinuation of linezolid due to AEs. The standard dosage of linezolid is effective and safe in children with bacterial infections (MIC ≤2 µg/mL). For pathogens with MIC >2 µg/mL, it is advisable to switch antibiotics or increase dosage.CLINICAL TRIALSThis study is registered with Chinese Clinical Trial Registry as ChiCTR 2200061207.

Background Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years, representing a major global healthcare burden. There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life. A multidisciplinary consensus development group comprising experts in epidemiology, infectious diseases, respiratory medicine, and methodology aims to develop the current consensus to address clinical issues of RSV infections in children. Data sources The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, using variations in terms for “respiratory syncytial virus”, “RSV”, “lower respiratory tract infection”, “bronchiolitis”, “acute”, “viral pneumonia”, “neonatal”, “infant” “children”, and “pediatric”. Results Evidence-based recommendations regarding diagnosis, treatment, and prevention were proposed with a high degree of consensus. Although supportive care remains the cornerstone for the management of RSV infections, new monoclonal antibodies, vaccines, drug therapies, and viral surveillance techniques are being rolled out. Conclusions This consensus, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections. Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.

ObjectiveMetagenomic next-generation sequencing (mNGS) was used to analyze the etiological distribution of refractory pneumonia in children. We compared its efficacy in pathogen diagnosis against traditional methods to provide a basis for clinical adjustment and treatment.MethodsA total of 60 children with refractory pneumonia treated at the Department of Respiratory Medicine, Children’s Hospital Affiliated with the Capital Institute of Paediatrics, from September 2019 to December 2021 were enrolled in this study. Clinical data (including sex, age, laboratory tests, complications, and discharge diagnosis) and lower respiratory tract specimens were collected, including bronchoalveolar lavage fluid (BALF), deep sputum, pleural effusion, lung abscess puncture fluid, traditional respiratory pathogens (culture, acid-fast staining, polymerase chain reaction, serological testing, etc.), and mNGS detection methods were used to determine the distribution of pathogens in children with refractory pneumonia and to compare the positive rate and diagnostic efficiency of mNGS and traditional pathogen detection for different types of pathogens.ResultsAmong the 60 children with refractory pneumonia, 43 specimens were positive by mNGS, and 67 strains of pathogens were detected, including 20.90% (14 strains) of which were Mycoplasma pneumoniae, 11.94% (8 strains) were Streptococcus pneumoniae, 7.46% (5 strains) were cytomegalovirus, and 5.97% (4 strains) were Candida albicans. Thirty-nine strains of Mycoplasma pneumoniae (41.03%, 16 strains), Streptococcus pneumoniae (10.26%, 4 strains), Candida albicans (7.69%, 3 strains), and Aspergillus (5.13%, 2 strains) were detected using traditional methods. The positive rate of mNGS detection was 90.48%, and the positive rate of the traditional method was 61.90% (p = 0.050), especially for G+ bacteria. The positive rate of mNGS was greater than that of traditional methods (p < 0.05), but they had no significant difference in detecting G- bacteria, viruses, fungi, or Mycoplasma/Chlamydia. Among the 60 patients, 21 had mixed infections, 25 had single infections, and the other 14 had unknown pathogens. Mycoplasma pneumoniae was most common in both mixed infections and single infections. The sensitivity, specificity, positive predictive value, and negative predictive value of mNGS were 95.45, 37.50, 80.77, and 75.00%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the traditional methods were 72.72, 62.50, 84.21, and 45.45%, respectively. The clinical compliance of mNGS was 80.00%, and that of the traditional method was 70.00%. The sensitivity and negative predictive value of mNGS were high, and the difference in the sensitivity for detecting G+ bacteria was statistically significant (p < 0.05). However, the differences in G- bacteria, fungi, and Mycoplasma/Chlamydia were not statistically significant (p > 0.05). Due to the small sample size, statistical analysis could not be conducted on viral infections.ConclusionmNGS has higher overall efficacy than traditional methods for the etiological diagnosis of refractory pneumonia in children. The application of mNGS can significantly improve the detection rate of pathogens in children with refractory pneumonia. The sensitivity and negative predictive value of mNGS for detecting G+ bacteria are greater than those of other methods, and it can exclude the original suspected pathogenic bacteria. Unnecessary antibiotic use was reduced, but there was no statistically significant difference in G- bacteria, fungi, or Mycoplasma/Chlamydia.

To the Editor: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. To date, over 2000 CFTR mutations have been identified. CF mostly occurs in the Caucasian population, and its incidence is approximately 1/25,000 to 1/1800.However, the number of CF cases in China is small. To discover the gene mutations and clinical characteristics of Chinese children with CF, as well as their correlation, the clinical data of 10 children with CF or CFTR-related disorders (CFTR-RD) were retrospectively analyzed in this study. Children with newly diagnosed CF or CFTR-RD were hospitalized at the Children's Hospital Affiliated to the Capital Institute of Pediatrics from June 2015 to August 2021 were enrolled. This study was approved by the Ethics Committee of the Capital Institute of Pediatrics (No. SHERLL2021013), and all patients have signed informed consent forms. The diagnostic criteria were as follows:(1) Sweat chloride values ≥60 mmol/L; or (2) Sweat chloride values in the intermediate range (30–59 mmol/L) in the presence of CF-causing CFTR mutations or CFTR dysfunction approved by CFTR physiologic testing. However, individuals with clinical features that might be consistent with CF who had a sweat chloride <30 mmol/L were less likely to have CF.[1] The children's basic data were collected from the electronic medical record system at our hospital. The blood samples of children and their parents were sent to testing institutions (Beijing MyGenostics Co., Ltd, China and Shanghai Hanyao Biomedical Technology Co., Ltd, China) for genetic tests and analysis. The mutated gene was identified by high-throughput sequencing and confirmed by Sanger sequencing. The test results classified the pathogenicity of the genetic variation according to the guidelines issued by the American College of Medical Genetics and Genomics (ACMG) in 2015. The CFTR2 (https//www.cftr2.org/), ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/), and CFTR-France (https://cftr.iurc.montp.inserm.fr/cftr/) databases were used to interpret the pathogenicity of CFTR variants. Sweat was collected for the quantitative detection of chloride ions. Among the 10 children, nine children were diagnosed with CF and one child was diagnosed with CFTR-RD, and all the parents and siblings had no clear history of CF. The age of onset was 29 days to 10 years, with a median age of four months. The age at diagnosis ranged from 10 months to 12.5 years, with a median age of 6.2 years. One children was Uyghur, and the rest were Han Chinese. The main manifestations were repeated cough, and wheezing and pulmonary infection in eight cases, two cases had low sodium, hypochloremia, and hypokalemia with mild cough, three cases had allergic bronchopulmonary aspergillosis (ABPA), and four cases had fatty diarrhea. In addition, there were two cases had intestinal obstruction, liver cirrhosis, diabetes, and pancreatitis [Supplementary Table 1, https://links.lww.com/CM9/B705]. The average value of the sweat chloride tests in nine children with CF was over 60 mmol/L. The sweat chloride test value of the child with CFTR-RD was 28 mmol/L. Sputum bacterial culture and next-generation sequencing were applied to find the etiology. The pathogenic examination of the nine CF children when first diagnosed revealed one case without infection and eight cases with Pseudomonas aeruginosa infection, among which four patients had additional bacterial infections. Pseudomonas aeruginosa was the most common infectious pathogen reported in China.[2] Spirometry and airway resistance tests with impulse oscillation were performed on nine of the 10 children, and seven cases had obstructive ventilation dysfunction to varying degrees. One of the remaining two patients had diffusion dysfunction, and the others had normal pulmonary function. Abdominal ultrasound was performed on all 10 children, including four with diffuse liver enlargement, three with abnormal pancreatic echo genicity, one with chronic inflammation of the intestinal wall, and two with normal tissue. All children with abnormal pancreatic echogenicity had clinical manifestations of fatty diarrhea. All 10 children underwent pulmonary computed tomography (CT) examination, and eight had bronchiectasis with varying degrees of "tree bud sign" and "signet ring sign". Thickening of the bronchial wall was seen in the other two patients. Nine children underwent sinus CT, which revealed sinusitis, mainly bilateral maxillary sinusitis, manifesting as thickening of the maxillary sinus mucosa or blockage of the sinus cavity. Electronic bronchoscopy was performed on nine children, all of whom had bronchitis changes. One patient had suppurative changes in the bronchial intima, and one patient had extensive squamous metaplasia of the bronchial mucosal epithelium. All 10 children underwent genetic testing (records were lost for case 7), a total of 16 mutations were found in this study. The homozygous CFTR variants were p. phe508del (phenylalanine deletion at position 508) (case 8) and p.Y325X (the nucleotide 975 in the coding region changed from thymine to guanine, resulting in the amino acid change of p.Y325X, which is a nonsense mutation)(case 10), the main clinical manifestation of the patient with p. phe508del was recurrent lung infections and steatorrhea, similar to the symptoms observed in the Caucasian population. The p.Y325X mutation was rarely reported, and the clinical manifestation of this patient was repeated fatty diarrhea, intestinal obstruction, and cough. The Sudan III dye test of fecal matter was positive. The chest high resoluation CT confirmed the presence of central bronchiectasis. The paranasal CT showed nasosinusitis. Abdominal CT showed that the pancreas had a high fat density. Nine new mutant nucleotides that were not previously included in the CFTR 2 database were found in this study. Two children with the p.phe508del mutation, rarely reported in China, were identified. One homozygous mutation and one heterozygous mutation were found, the homozygous mutation was found in a Uyghur child and the heterozygous mutation in a Han Chinese child [Supplementary Table 1, https://links.lww.com/CM9/B705]. Two children (case 1 and case 7) underwent double lung transplantation due to the continuous deterioration of lung function. The two children were girls aged 14 years and 13 years at the time of transplantation. At present, they are 3 years and 2 years after lung transplantation, respectively. Their pulmonary function and quality of life after lung transplantation improved. Studies have shown that the 5-year survival rate after lung transplantation could reach 60–70%, and 45% of CF patients could survive for 10 years after lung transplantation.[3] A boy died from recurrent intestinal obstruction at the age of 10. Children with fatty diarrhea were given pancreatin enteric-coated capsules orally. One child had CF-related diabetes and was treated with insulin. Three children with ABPA were treated with oral corticosteroids, and their cough and wheezing symptoms were improved. The other two cases mainly manifested as repeated electrolyte disorders, and pulmonary symptoms, such as cough and expectoration, were not obvious. Oral rehydration salt was administered to correct the electrolyte disorders. The median age at CF diagnosis is 8.7 years in Chinese patients, 0.5 month in European patients[5] and 3 months in American patients according to the 2017 Patient Registry Annual Data Report, indicating a significant delay in diagnosis in China. In our study, the median age at diagnosis was 6.2 years. The CFTR mutations are mainly divided into six classes. The gene mutation in two children in this study was p.phe508del, which was not commonly reported in China. Two children in this study had the p.G970D mutation, which is the most common mutation type in Chinese CF patients but is rare or absent in Caucasias.[4] In this report, there were two cases (cases 4 and case 5) with no obvious respiratory involvement who mainly presented with irreversible hyponatremia, hypochloremia, and hypokalemia after vomiting. At onset, the disease was first considered "Bartter syndrome", but there was no renal tubular damage. The patients were finally diagnosed with CF by the sweat chloride test and gene sequencing studies. Retrospective case studies by Shen et al[5] have also revealed that pseudo-Bartter syndrome can be the only or first manifestation of CF and p.G970D was the most frequent variant in cystic fibrosis-associated pseudo-Bartter syndrome (CF-PBS), with a significant ethnic association with the Chinese population, in which the genotypes differ from those observed in Caucasians. Case 9 had recurrent coughing, wheezing, and lung infections. The genetic test results revealed two variants, c.1405A >G and c.2977G >T. According to the ACMG guidelines, the mutation site c.1405A >G and c.2977G >T were determined to be unknown clinically significant mutations. However, the sweat chloride test was negative, and the disorder could not be diagnosed as CF, but as CFTR-RD. CFTR-RD is a disease with relevant clinical manifestations of CFTR dysfunction, but involving only one system, the detection of sweat chloride ion concentration is in the suspicious interval or normal, does not carry two clear CF pathogenic genes, and cannot meet the diagnostic criteria of CF.[6] Compared with CF patients, the clinical symptoms of CFTR-RD patients are often relatively mild, and the prognosis is relatively good. In contrast to other countries, CFTR mutations in China demonstrate substantial heterogeneity, and many previously unreported CFTR mutant genes are being found. Sweat chloride tests and genetic analysis are actively carried out to enrich the CFTR mutation spectrum, which is of great significance to the individualized diagnosis and treatment of children with CF in the future. Funding This work was supported by a grant from the Special Fund of Pediatric Coordinated Development Center of Beijing Hospitals Authority (No. XTCX2018021). Conflicts of interest None.

Recombination events in human adenovirus (HAdV) have led to some new highly pathogenic or infectious types. It is vital to monitor recombinant HAdVs, especially in children with acute respiratory tract infections (ARIs). In the retrospective study, HAdV positive specimens were collected from pediatric patients with ARIs during 2015 to 2021, then typed by sequence analysis of the penton base, hexon and fiber gene sequence. For those with inconsistent typing results, a modified method with species-specific primer sets of a fiber gene sequence was developed to distinguish co-infections of different types from recombinant HAdV infections. Then, plaque assays combined with meta-genomic next-generation sequencing (mNGS) were used to reveal the HAdV genomic characteristics. There were 466 cases positive for HAdV DNA (2.89%, 466/16,097) and 350 (75.11%, 350/466) successfully typed with the most prevalent types HAdV-B3 (56.57%, 198/350) and HAdV-B7 (32.00%, 112/350), followed by HAdV-C1 (6.00%, 21/350). Among 35 cases (7.51%, 35/466) with inconsistent typing results, nine cases were confirmed as co-infections by different types of HAdVs, and 26 cases as recombinant HAdVs in six genetic patterns primarily clustered to species C (25 cases) in pattern 1–5, or species D (1 case) in pattern 6. The novel recombinant HAdV of species D was identified with multiple recombinant events among HAdV-D53, HAdV-D64, and HAdV-D8, and officially named as HAdV-D115. High-frequency recombination of HAdVs in six genetic recombination patterns were identified among children with ARIs in Beijing. Specifically, there is a novel Adenovirus D human/CHN/S8130/2023/115[P22H8F8] designed as HAdV D115.

ObjectiveThe study aims to analyze the clinical characteristics of acute phase of SARS-CoV-2 infection in children aged 0–17 years with the Omicron variant, and summarize the persistent symptoms or new-onset clinical manifestations from 4 to 12 weeks after acute COVID. Explore the association between the vaccination status and SARS-CoV-2 neutralizing antibody levels post infection among preschool-aged children. The comprehensive study systematically describes the clinical characteristics of children infected with SARS-CoV-2, providing a foundation for diagnosis and evaluating long-term COVID in pediatric populations.MethodsThe study enrolled children who were referred to the Children's Hospital, Capital Institute of Pediatrics, (Beijing, China) from January 10, 2023 to March 31, 2023. Participants were classified as infant and toddlers, preschool, school-age, and adolescent groups. Children or their legal guardians completed survey questionnaires to provide information of previous SARS-CoV-2 infection history, as well as clinical presentation during the acute phase and long-term symptoms from 4 to 12 weeks following infection. Furthermore, serum samples were collected from children with confirmed history of SARS-CoV-2 infection for serological testing of neutralizing antibodies.ResultsThe study recruited a total of 2,001 children aged 0–17 years who had previously tested positive for SARS-CoV-2 through nucleic acid or antigen testing. Fever emerged as the predominant clinical manifestation in 1,902 (95.1%) individuals with body temperature ranging from 37.3 to 40.0°C. Respiratory symptoms were identified as secondary clinical manifestations, with cough being the most common symptom in 777 (38.8%) children, followed by sore throat (22.1%), nasal congestion (17.8%), and runnning nose (17.2%). Fatigue (21.6%), headache (19.8%) and muscle-joint pain (13.5%) were frequently reported systemic symptoms in children. The proportion of children with symptoms of SARS-CoV-2 infection varied across age groups. 1,100 (55.0%) children experienced persistent symptoms from 4 to 12 weeks post the acute phase of infection. Trouble concentrating (22.1%), cough (22.1%), and fatigue (12.1%) were frequently reported across age groups in the extended period. A limited number of children exhibited cardiovascular symptoms with chest tightness, tachycardia, and chest pain reported by 3.5%, 2.5%, and 1.8% of children, respectively. Among 472 children aged 3–5 years, 208 children had received two doses of SARS-CoV-2 vaccine at least 6 months prior to infection, and no association was found between the incidence of long-term COVID and pre-infection vaccination statuses among the 3–5 years age groups (χ2 = 1.136, P = 0.286).ConclusionsIn children aged 0–17 years infected with SARS-CoV-2 Omicron variant, fever was the primary clinical manifestation in the acute phase, followed by respiratory symptoms, systemic non-specific and digestive presentations. In particular, respiratory and digestive system symptoms were more frequent in children aged above 6 years. Regarding the long-term symptoms from 4 to 12 weeks post-infection, the most common presentations were concentrating difficulty, cough, and fatigue. The incidence of persistent symptoms of SARS-CoV-2 did not exhibit a significant correlation with vaccination status, which was attributed to the waning efficacy of the vaccine-induced humoral immune response after 6 months.

There were several factors associated with respiratory syncytial virus (RSV) severe acute lower respiratory infection (RSV-sALRI) in infants and young children. It is vital to develop a convenient scoring system to predict RSV-sALRI in children. Pediatric patients with RSV-ALRI from January 2009 to December 2021 were recruited retrospectively. Two-third of them were randomly grouped into the development set and one-third to the validation set. In the development set, risk factors for RSV-sALRI were transferred into the logistic regression analysis, then their receiver operating characteristic (ROC) curves were built to obtain the area under the ROC curve (AUC), and regression coefficients for each predictor were converted to points. Finally, the value of the scoring system was evaluated in the validation set. A total of 1 066 children with RSV-ALRI were recruited, including 710 in the development set and 356 in the validation set. By logistic regression analysis, six factors (younger than 2 years, gestational age <37 weeks, have siblings, birth weight ≤2500 g, artificial/mix feeding, CHD) showed statistical difference and then were scored with points according to the coefficient value (OR) in the development set. In the validation set, the sensitivity of the scoring system was 70.25%, the specificity 85.53%, the positive predictive value 71.43%, the negative predictive value 84.81%, and coincidence rate 0.80. The Kolmogorov–Smirnov test showed the distribution of AUC 0.765 (SE = 0.027; 95% CI = 0.713–0.818; p < 0.001). A simplified scoring system was developed in the study with high prediction value for RSV-sALRI in children.

We collected respiratory specimens from 128 pediatric patients diagnosed with pneumonia in Beijing in late 2023. Mycoplasma pneumoniae was detected in 77.3% (99/128) patients, with 36.4% (4/11), 82.9% (34/41), 80.3% (61/76) in children aged less than 3 years, 3–6 years, over 7 years, respectively. Mycoplasma pneumoniae (M. pneumoniae) was characterized using P1 gene typing, MLVA typing and sequencing of domain V of the 23S rRNA gene. P1 gene type 1 (P1-1; 76.1%, 54/71) and MLVA type 4-5-7-2 (73.7%, 73/99) were predominant. MLVA identified a new genotype: 3–4–6-2. Macrolide resistance-associated mutations were detected in 100% of samples, with A2063G accounting for 99% and A2064G for 1%. The positive rate of M. pneumoniae was higher compared to previous reports, especially in children less than 3 years, suggesting a M. pneumoniae epidemic showing a younger age trend occurred in late 2023 in Beijing, China. Higher proportions of macrolide-resistant M. pneumoniae, P1-1 and 4-5-7-2 genotype M. pneumoniae indicated increased macrolide resistance rate and genotyping shift phenomenon, which might be attributable to this epidemic. Additionally, complete clinical information from 73 M. pneumoniae pneumonia inpatients were analyzed. The incidence of severe M. pneumoniae pneumonia was 56.2% (41/73). Mycoplasma pneumoniae pneumonia patients exhibited longer duration of fever, with a median value of 10.0 days (IQR, 8.0–13.0), and higher incidence of complications (74.0%, 54/73). However, in this cohort, we found that the severity of M. pneumoniae pneumonia, co-infection, or complications were not associated with M. pneumoniae P1 gene or MLVA types. Clinicians should be aware that patients infected with macrolide-resistant M. pneumoniae exhibited more severe clinical presentations.

Background: Variations in the fusion (F) protein of respiratory syncytial virus (RSV) with main antigenic sites I–V and Ø may affect the development of RSV vaccines and therapies. Methods: In the study, 30 respiratory specimens positive for RSV were randomly selected from children with acute lower respiratory infections (ALRI) in Beijing every year from 2012 to 2021 for F gene sequencing. Then, 300 F gene sequences and 508 uploaded to GenBank from China were subjected to phylogenetic analysis. Results: The results indicated the nucleotide identities were 95.4–100% among 446 sequences of RSV A, and 96.3–100% among 362 of RSV B. The most common variant loci were N80K (100.00%) and R213S (97.76%) for site Ø, and V384I/T (98.43%) for site I among sequences of RSV A, and M152I (100.00%), I185V (100.00%), and L172Q/H (94.48%) for site V, and R202Q (99.45%) for site Ø among sequences of RSV B. N276S appears in 95.29% sequences of RSV A, while S276N and N262 I/S appear in 1.38% and 0.55% sequences of RSV B, respectively. No variation was found in all sequences at the binding sites of 14N4 and motavizumab. Conclusions: There were cumulative variations of the RSV F gene, especially at some binding sites of antigenic sites.

Acute respiratory distress syndrome(ARDS) is an important pathological process in patients with severe viral pneumonia.The coagulation disorder is one of the important characteristics of patients with viral pneumonia.In recent years, more and more studies have been exploring the related mechanisms of ARDS caused by viral pneumonia.Although the application of low molecular weight heparin(LMWH) to prevent and treat thrombotic complications in patients with viral pneumonia has become an industry consensus, in addition to anticoagulation, LMWH also has multiple effects such as anti-inflammatory and antioxidant.Therefore, the therapeutic effect of LMWH on ARDS remains to be fully explored.This article focuses on the pathological and clinical characteristics of viral pneumonia, to explore the evidence and clinical mechanisms of LMWH in the treatment of ARDS.

社区获得性肺炎(community acquired pneumonia,CAP)是全球儿童感染的原因之一,本病在儿科领域尤为常见,且对5岁以下儿童造成的伤害较为显著.CAP发病率及死亡率相对其他呼吸系统疾病更高,使患儿身心均受到巨大损害,不利于儿童健康成长.CAP的致病微生物复杂多样,且不同年龄、季节、地区病原分布差异明显,这在一定程度上造成临床诊治困难,因此,早期明确病种尤其重要.基于此,本文对近年来儿童CAP的流行病学情况及病原感染情况进行了综述.

The common human coronaviruses (HCoVs) HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 which are members of the coronavirus family are long co-existed with humans and widely distributed globally. Common HCoVs usually cause mild, self-limited upper respiratory tract infections (URTI), and also associated with lower respiratory tract infections (LRTI), especially in children. However, there are little multicentre studies have been conducted in children of several different areas in China, and the epidemic potential of common HCoVs remains unclear. Understanding of the common HCoVs is valuable for clinical and public health. Herein, we retrospectively analysed the medical records of children with acute lower respiratory tract infection admitted to 9 hospitals from different regions in China from 2014 to 2019. Of the 124 patients who tested positive for coronaviruses, OC43 was the predominant type, accounting for 36.3% (45/124) of the detections. Children aged ≤ 6 months and 12–23 months had the highest detection rate of common HCoVs, and the detection rate gradually declined after 2 years old. These four HCoVs could be detected all year round. Among the areas of our study, the overall positive rate was higher in southern China, especially in Guangzhou (29/124, 23.4%). Moreover, common HCoV-positive patients were codetected with 9 other common respiratory pathogens. 229E (11/13, 84.6%) was the most frequently associated with codetection, with EV/RhV was the most frequently codetected virus. Cough (113/124, 91.1%) and fever (73/124, 58.9%) were the most common symptoms of common HCoVs infection.