Jun Shen

Background: Fulminant myocarditis (FM) is a life-threatening inflammatory cardiac disease in children, frequently triggered by viral infections. Although mechanical circulatory support has improved short-term survival, data on viral etiology and long-term outcomes remain limited, particularly in Asian populations. Methods: We conducted a mixed retrospective–prospective analysis of pediatric FM patients at the Children’s Hospital of Fudan University from 2015 to 2025. Clinical data from 2015 to 2023 were collected retrospectively, while data from 2024 onward were collected prospectively. Clinical data, microbiological findings (PCR and metagenomic next-generation sequencing), treatment strategies, and outcomes were extracted from electronic medical records. Follow-up data for survivors were collected through December 2025. Results: A total of 53 children with FM were included. Median age was 91.5 months; 43.4% were male, and 56.6% were female. Common presenting symptoms included fever (64.2%) and vomiting (56.6%). Microbiological evidence was identified in 11 patients (20.8%), with rhinovirus (5.7%) and influenza virus (5.7%) being the most frequent, followed by enterovirus (3.8%) in peripheral specimens. During hospitalization, 79.2% required mechanical ventilation, 64.2% received extracorporeal membrane oxygenation (ECMO), and 45.3% underwent continuous renal replacement therapy (CRRT). Intravenous immunoglobulin (IVIG) was administered to 84.9%. In-hospital mortality was 13.2% (7/53), and 17.0% (9/53) of patients were discharged against medical advice (DAMA). Among 35 followed patients (median 12.4 months), most achieved favorable cardiac recovery; however, persistent conduction abnormalities, structural cardiac changes, and neurological sequelae were observed in a minority. Conclusions: Pediatric FM carries substantial in-hospital morbidity and resource utilization, despite favorable recovery rates in most survivors. The low pathogen detection rate in peripheral blood and the lack of endomyocardial tissue sampling preclude definitive conclusions regarding the underlying etiology, whether active viral replication or immune-mediated injury predominates. Endomyocardial biopsy-based investigations are urgently needed to clarify the underlying pathobiology.

Enterovirus D68 (EV-D68) is a re-emerging pathogen associated with severe acute flaccid myelitis (AFM) and pneumonia, predominantly in children but also capable of causing severe disease in immunocompromised adults. Seroprevalence data are essential for understanding population immunity, age-specific susceptibility, and viral transmission dynamics; yet, such data for the period after the COVID-19 pandemic are scarce. We conducted a cross-sectional serological survey to characterize the neutralizing antibody profile of EV-D68 among children in Xiamen, China, in 2022. A total of 453 children aged 0–16 years (217 with acute respiratory tract infection [ARTI] and 236 without) were enrolled. Neutralizing antibody (NtAb) titers against the EV-D68 STL strain were measured using a microneutralization assay, seropositivity was defined as a titer ≥1:16. Multivariable regression and analysis of covariance were used to adjust for age and sex. Overall seroprevalence was 96.0% (435/453), exceeding 90.0% in every age subgroup (0–1 y: 100%; 1–3 y: 97.6%; 3–5 y: 92.6%; ≥5 y: 96.2%). The geometric mean titer (GMT) was 76.78 (95% CI: 68.32–85.24). After adjustment, ARTI status was not significantly associated with seropositivity (adjusted OR = 1.42, 95% CI: 0.46–4.41, p = 0.542). In an exploratory comparison, children with ARTI showed nominally higher antibody titers than those without (Mann–Whitney U test, p = 0.003), although the absence of EV-D68-specific PCR testing precludes etiologic attribution of respiratory symptoms to EV-D68 infection. Infants < 1 year showed the highest GMT (86.31), while children aged 1–3 years had the lowest GMT (63.52) and the largest low-titer fraction, indicating a susceptibility gap. Our study revealed EV-D68 circulated endemically in this pediatric population, establishing a high population immune baseline (>90.0%) with distinct age-dependent patterns. These findings provide key reference data for ongoing serosurveillance, outbreak risk assessment, and the evaluation of future vaccines or immunoprophylactic strategies should they become available.

Enterovirus D68 (EV-D68) causes severe respiratory diseases and acute flaccid myelitis (AFM), for which no licensed vaccines or therapeutics are currently available. Neutralizing antibodies (nAbs) block infection via binding capsid epitopes. This review summarizes the EV-D68 antigenic structure, nAb mechanisms (receptor blockade and conformational disruption), therapeutic prospects of nAbs, and vaccine progress (inactivated, virus-like particle [VLP], and nucleic acid). Key challenges, like antigenic drift and blood-brain barrier (BBB) penetration, are also highlighted to guide countermeasure development.

Introduction: The persistent circulation of influenza viruses following the COVID-19 pandemic remains a major public health concern, yet local genomic epidemiology in pediatric populations is not well-defined. Methods: In 2024, we collected 490 influenza antigen-positive specimens from a pediatric hospital in Qidong, eastern China, and performed influenza genome enrichment-based whole-genome sequencing, yielding 425 genomes (86.73%) with at least hemagglutinin (HA) and neuraminidase (NA) segments. Results: A/H1N1 (45.41%), A/H3N2 (18.35%), and B/Victoria (36.24%) co-circulated, with two activity peaks in January and December. Phylogenetic analysis assigned these viruses to clades 6B.1A.5a.2a (A/H1N1), 3C.2a1b.2a.2a.3a.1 (A/H3N2), and V1A.3a.2 (B/Victoria). Positively selected sites in HA included lineage-specific residues such as position 210 in B/Victoria and positions 187 and 372 in A/H3N2. The oseltamivir resistance marker NA-H275Y was detected in 7/193 (3.65%) A/H1N1 strains, whereas no detected resistance to RNA polymerase inhibitors. Discussion: These findings highlight the co-circulation patterns, genetic diversity, and antiviral susceptibility profile of influenza viruses in a pediatric population in eastern China, supporting the importance of sustained genomic surveillance to guide local prevention strategies and clinical management.

Enterovirus D68 (EV-D68), a neurotropic respiratory pathogen, poses a considerable clinical threat through its link to pediatric acute flaccid myelitis (AFM) and severe respiratory illness. The possibility of recurrent epidemics, evidenced since the 2014 outbreak, remains a major concern. Genomic determinants of virulence are central to this threat. Sequence variations that affect host–receptor interactions, immune evasion, and replication efficiency serve as critical modifiers of pathogenicity. This article systematically reviews the evidence for specific genomic sites that enhance EV-D68 virulence, focusing on three critical regions: the VP1 receptor-binding site, the 2Apro/TRAF3 cleavage site, and the 3Cpro immunoregulatory region. Mutations in the VP1 receptor-binding site can alter affinity for host receptors such as sialic acid, heparan sulfate, and MFSD6, thereby shaping viral entry and tissue tropism. Alterations in the 2Apro/TRAF3 cleavage site may impair proteolytic cleavage of host TRAF3, attenuating immune evasion and reducing viral pathogenicity. Variations in the 3Cpro region affect its efficiency in cleaving host proteins involved in translation and autophagy, ultimately modulating viral replication and antiviral responses. Finally, we propose that monitoring for mutations in these key virulence determinants, particularly within the surface-exposed VP1, is essential for effective outbreak preparedness.

Enterovirus D68 (EV-D68) is an emerging pathogen that causes severe respiratory infections in children worldwide and has the potential to re-outbreak. The aim of this study was to assess EV-D68 detection and genetic variability in pediatric patients with community-acquired pneumonia (CAP) during and after the COVID-19 pandemic in China. Respiratory samples, including bronchoalveolar lavage fluid (BALF), were collected from hospitalized children with CAP in Shanghai, Shandong, Fujian, Zhejiang and Jiangsu province between January 1, 2021 and December 31, 2024. Samples were screened for EV-D68 using real-time RT-PCR, and clinical characteristics of positive cases and virus strain sequences were analyzed. Of 2,842 cases, 0.7% (21/2,842) positive with EV-D68. The median age of these patients was 5.0 years (IQR: 3.6-8.0 years), with 42.9% (9/21) presented severe CAP. Of the 21 identified virus strains, 15 belonged to subclade B3 and 6 to subclade D3. In 2024, a total of 14 strains were detected, including 6 from the newly emerged subclade D3. Seven strains, 5 of which were subclade D3, were found in BALF samples from severe CAP patients. One child with severe CAP exhibited subclade D3 EV-D68 viremia. Notable mutations in the VP1 protein included H99D, K168E, and E169K. Our research showed that the EV-D68 continued to spread among children in eastern China before and after the COVID-19 pandemic. From 2021 to 2024, subclades B3 and D3 predominated, with increase detections in 2024 and association with pediatric severe CAP.

Objective: Brainstem encephalitis (BE) can cause sudden death in children. Fewer studies have been conducted on the incidence, clinical manifestations, pathogens and post-infectious sequelae of pediatric infectious BE. Methods: Pediatric patients diagnosed with BE in our Medical Center from 01 January 2015 to 31 July 2024 were retrospectively reviewed. The clinical data of these children were obtained from the hospital’s medical database on 15 August 2024. The number of outpatient and inpatient patients at our Medical Center during that period were provided by the hospital data center. Data analysis was conducted using Excel 2019. Results: A total of twenty-eight cases were diagnosed with BE in our National Children′s Medical Center over the past decade. Among them, 57.1% (16/28) cases were diagnosed with infectious BE. The incidence of infectious BE was estimated to be 16 cases per 30 million outpatient visits and 13 cases per 500,000 hospitalized patients. Fever, consciousness disorders and seizures were observed in 75.0% (12/16), 68.8% (11/16) and 62.5% (10/16) of the cases, respectively. Among them, 31.3% (5/16) cases were diagnosed as human enterovirus infections, 12.5% (2/16) cases were confirmed to be influenza B virus infections, while one case each was diagnosed with herpes simplex virus 1 and human herpesvirus 6 infection. The mortality rate during hospitalization was 12.5% (2/16). Among the surviving patients, 50.0% (7/14) of them had follow-up records, 85.7% (6/7) of the survivors suffered from sequelae such as motor disorders. Conclusion: Fever, consciousness disorders and seizures were the major clinical manifestations in patients with infectious BE visited our Medical Center. These rare cases exhibited a notably high mortality rate and a significant frequency of long-term complications.

Background Receiving multiple micronutrient supplementations (MMS) in developing countries has demonstrated favorable effects on birth outcomes. The objective of this review is to assess the effectiveness of MMS interventions in relation to the long-term physical and cognitive development of children. Methods We conducted a comprehensive search for eligible studies through databases in May 2023. Meta-analyses were conducted using Stata, version 15, on all randomized controlled trials (RCTs) that evaluated the long-term developmental outcomes of children by assessing the impact of preconceptional and antenatal MMS. Results The review encompassed a total of twelve studies. The trials included a total of 13,899 pregnant women and 12,986 children, serving as the foundation for individual participant data meta-analyses MMS involving iron plus folic acid supplementation (IFAS). Our analysis revealed that MMS did not demonstrate any significant improvements in key anthropometric and body composition measurements, including weight-for-age z score (WAZ) (Mean Difference [MD]: 0.01; 95% Confidence Interval [CI]: -0.05 to 0.07), height-for-age z score (HAZ) (MD: 0.00; 95% CI: -0.05 to 0.05), Body Mass Index (BMI)-for-age (MD: 0.04; 95% CI: -0.04 to 0.12), weight-for-length z score (WLZ) (MD: 0.00; 95% CI: -0.07 to 0.08), head circumference (HC) (MD: 0.06; 95% CI: -0.05 to 0.17), and mid-upper arm circumference (MUAC) (MD: 0.04; 95% CI: -0.04 to 0.12). However, the administration of prenatal MMS exhibited a significant positive correlation with the enhancement of children's Full Scale Intelligence Quotient (FSIQ) scores (MD: 0.97, 95% CI: 0.09 to 1.84). Conclusions The antenatal maternal MMS interventions do not appear to have a discernible impact on child growth outcomes. However, there is potential evidence suggesting that maternal MMS interventions may positively influence the cognitive development of offspring. Trial registration: CRD42023428221 (31/05/2023)