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  Abstract SARS-CoV-2 infections in children occasionally manifest with severe neurologic signs . We report a case series of life-threatening encephalopathy associated with SARS-CoV-2 in 25 children in Australia, Japan, Singapore, and Taiwan during February 2022–January 2024. All children had severe encephalopathy develop, characterized by rapidly progressive cerebral edema , conditions known as acute shock with encephalopathy and multiorgan failure or acute fulminant cerebral edema . Among the 25 patients, 22 (88%) eventually died ; 11 (44%) children died within 24 hours of hospitalization. In addition, 18 (72%) had illness manifest with shock, and 14 (56%) had multiorgan failure develop within 6 hours of neurologic onset. Serum concentrations of cytokines/chemokines including interleukin 6 and tumor necrosis factor-α were significantly higher within 24 hours of onset than for controls. SARS-CoV-2–associated encephalopathy cases such as those described here represent an emerging n...

  Highlights •  Viremia in children with La Crosse Virus infection is transient; viral RNA was detected in only 3.2% of sera •  Detection of La Crosse Virus RNA in respiratory samples is slightly higher at 21.7% and may reflect the temporal distribution of the virus after infection •  NAAT has limited utility in routine diagnosis of La Crosse Virus encephalitis in children but may still be useful in cases with delayed seroconversion Abstract Background La Crosse virus (LACV), a member of family Peribunyaviridae, genus Orthobunyavirus , is the leading cause of neuroinvasive arboviral infection in children in the United States . Diagnosis relies on detecting specific antibodies (IgG or IgM), a 4-fold titer rise or seroconversion, in patients with compatible presentations. NAAT used for LACV detection has largely been limited to mosquito, animal models or postmortem brain tissue. There is a lack of data on the performance of NAATs in clinical specimens from living patie...

Abstract Highly pathogenic avian influenza A (H5N1) (H5N1 hereafter) is an emerging pathogen in mammals . The recent recognition of H5N1 in dairy cattle increases opportunities for human exposure and infection and may accelerate a trajectory toward sustained human-to-human transmission . Furthermore, the presence of virus at high concentration in unpasteurized milk raises new risks for humans , especially infants and children . Milk has been identified as a vehicle for viral transmission in and between mammalian species, including humans. Sialic acids (SAs) found on cell surfaces are important mediators of species susceptibility to specific influenza strains and play an important role in viral tropism . New data demonstrate that SA receptors with α2,3 linkages capable of binding avian influenza strains are present in human mammary tissue . The presence of SA receptors that can bind avian influenza and a comparative analysis of viral transmission risk of raw and pasteurized milk in seve...

  Summary Highly pathogenic avian influenza A(H5N1) viruses have been circulating among wild birds and are enzootic in poultry in some areas of the world with spillover to a wide range of terrestrial and marine mammals. Since 1997, sporadic animal to human , primarily poultry to human, transmission of highly pathogenic avian influenza A(H5N1) viruses has been reported in 25 countries . More recently there have been locally acquired infections in the Americas due to the 2.3.4.4b clade of the virus. Most of the recently detected human infections in the USA have been relatively mild but there have been cases of critical illness reported in several countries. In this Grand Round we present the first locally acquired highly pathogenic avian influenza A(H5N1) virus infection in Canada , which was in a 13-year-old female, who developed severe disease requiring prolonged critical care . She was infected with a clade 2.3.4.4b, genotype D1.1 virus and developed evidence of cytokine storm and...

  Abstract Objective :  This systematic review aimed to assess the clinical effectiveness and safety profile of baloxavir marboxil for managing influenza in pediatric populations . Methods :  This review has been registered on the INPLASY platform (INPLASY2025110063). Designed in accordance with the PRISMA 2020 guidelines, we searched four major biomedical databases (PubMed, Embase, Web of Science, Cochrane Library) covering publications from January 1, 2015, to January 30, 2025 . Eligibility criteria encompassed both randomized controlled trials and observational cohort studies evaluating this antiviral agent in children with laboratory-confirmed influenza. Methodological rigor was appraised using the Cochrane Collaboration's risk of bias instrument for randomized controlled trials (RCTs) and the Newcastle-Ottawa Quality Assessment Scale for cohort studies. Statistical synthesis was conducted using RevMan 5.3 software (Version 5.3.5) with metafor package implementation. ...

  Abstract Influenza-associated encephalitis/encephalopathy (IAE) is a severe neurological complication characterized by central nervous system dysfunction and structural damage following influenza virus infection . Predominantly affecting infants and young children , IAE exhibits its highest incidence in those under five years of age . Key clinical manifestations of IAE include acute seizures, sudden high fever, and impaired consciousness , frequently progressing to coma . Neuroimaging , particularly magnetic resonance imaging (MRI), often reveals multifocal brain lesions involving multiple brain regions, including the cerebellum, brainstem, and corpus callosum . The prognosis of IAE is poor , with a mortality rate reaching 30%. Current diagnosis relies heavily on clinical presentation and characteristic neuroimaging findings, as the precise pathogenesis of IAE remains elusive . While various research models, including cell lines, brain organoids, and animal models , have been dev...

  Summary Background Lower respiratory infections (LRIs) remain the world's leading infectious cause of death. This analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides global, regional, and national estimates of LRI incidence, mortality, and disability-adjusted life-years (DALYs), with attribution to 26 pathogens , including 11 newly modelled pathogens, across 204 countries and territories from 1990 to 2023. With new data and revised modelling techniques, these estimates serve as an update and expansion to GBD 2021. Through these estimates, we also aimed to assess progress towards the 2025 Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) target for pneumonia mortality in children younger than 5 years. Methods Mortality from LRIs, defined as physician-diagnosed pneumonia or bronchiolitis, was estimated using the Cause of Death Ensemble model with data from vital registration, verbal autopsy, surveillan...

  Abstract This study assessed the epidemiological and microbiological invasive pneumococcal disease (IPD) changes that occurred before and after the emergence of COVID-19 in Italy . All IPD cases reported through the nationwide surveillance system during 2018–2023 were included. IPD incidence and serotype distributions were analyzed by age group. IPD incidence in 2020–2021 declined in all age groups compared with 2018–2019 , especially in children less than 2 years of age and elderly people aged > 64 years. A resurgence of IPD cases was observed from late 2022 onwards , with values in children exceeding those seen before the pandemic. The post COVID-19 increase in children was mainly driven by some PCV13 serotypes , such as 3, 19A, and 19F , but also non-vaccine serotypes, including 10A, 8, and 24F , while in the elderly population , a predominance of serotypes 3 and 8 was observed . In conclusion, a steep drop in IPD incidence was observed during the peak of the COVID-19 pande...

  Summary Background Following a decline during the COVID-19 pandemic, Mycoplasma pneumoniae infections resurged in several countries . We aimed to characterise the clinical presentation of paediatric patients admitted to hospital for M pneumoniae during 2023 and 2024 in France. Methods We conducted a nationwide, multicentre, retrospective, and prospective observational study across 37 French paediatric hospitals (September, 2023–September, 2024). Children younger than 18 years who were hospitalised with laboratory-confirmed M pneumoniae infection (PCR or serology) were included. Demographics (excluding race), clinical features, laboratory and radiological findings, management, and outcomes data were described and analysed. Logistic regression was used to identify factors associated with paediatric intensive care unit (PICU) admission. The trial was registered at ClinicalTrials.gov (NCT06260371) and is complete. Findings We included 969 children and adolescents with M pneumoniae in...

  Abstract Background Changes in the vaccine advisory process in the United States have disrupted immunization guidance , which reinforces the need for independent evidence review to inform decisions regarding immunization for respiratory viruses during the 2025–2026 season. Methods We conducted a systematic review of U.S.-licensed immunizations against coronavirus disease 2019 (Covid-19), respiratory syncytial virus (RSV), and influenza . We searched databases on PubMed/MEDLINE, Embase, and Web of Science for updates of the most recent review by the Advisory Committee on Immunization Practices (ACIP) Evidence-to-Recommendations for each disease, which was performed during the 2023–2024 period. Outcomes included vaccine efficacy and effectiveness against hospitalization, other clinical end points, and safety. Results Of 17,263 identified references, 511 studies met the inclusion criteria. Covid-19 mRNA vaccines against the XBB.1.5 subvariant had pooled vaccine effectiveness against...

  Summary Background Since October, 2023, Palestinian children in the Gaza Strip have suffered war-induced displacement, food insecurity, malnutrition, and elevated risks of famine and mortality . In this study, we aimed to document the extent of, and patterns in, wasting malnutrition in children aged 6–59 months across the Gaza Strip between January, 2024, and August, 2025. Methods This longitudinal, cross-sectional, surveillance study was conducted across a total of 16 UN Relief and Works Agency for Palestine Refugees in the Near East health centres and 78 medical points established within school shelters and tent encampments across the five governorates of Gaza. Children aged 6–59 months were screened for wasting malnutrition by mid-upper arm circumference (MUAC) measurement. Children with a MUAC of less than 125 mm were enrolled into therapeutic feeding regimens. MUAC Z scores were derived from published WHO age-specific and sex-specific arm circumferential growth curves. Month...

  Abstract Background :  The purpose of this study was to retrospectively analyse the clinical presentation of RSV, Influenza , and SARS-CoV-2 infections in children across three consecutive seasons (2022/2023; 2023/2024; and 2024/2025).  Methods :  Of the 321 hospitalised patients , 129 ( 36% ) tested positive for RSV , 110 ( 38% ) for Influenza , and 82 ( 26% ) for SARS-CoV-2 . Children were aged ≤ 17 years (median: 15 months). The data were statistically analysed using the χ2 test, multinomial multivariable logistic regression, OR (odds ratio), and 95% CI (confidence interval).  Results :  Significant independent predictors of RSV infection were auscultatory abnormalities (OR: 15.9 [1.49–169]) and hospital admission ≥ 4 days after symptom onset (OR: 32.5 [1.19–907]). Among RSV-positive patients , compared with those aged < 6 months , those aged 7–24 months were more likely to present with higher CRP levels (OR 1.06 [1.003–1.13]), reduced appetite (OR ...

  Summary Background Post-acute sequelae of SARS-CoV-2 infection (PASC) remain a major public health challenge . Although previous studies have focused on characterising PASC in children and adolescents after an initial infection , the risks of PASC after reinfection with the omicron variant remain unclear. We aimed to assess the risk of PASC diagnosis (U09.9) and symptoms and conditions potentially related to PASC in children and adolescents after a SARS-CoV-2 reinfection during the omicron period. Methods This retrospective cohort study used data from 40 children's hospitals and health institutions in the USA participating in the Researching COVID to Enhance Recovery (RECOVER) Initiative. We included patients younger than 21 years at the time of cohort entry; with documented SARS-CoV-2 infection after Jan 1, 2022; and who had at least one health-care visit within 24 months to 7 days before the first infection. The second SARS-CoV-2 infection was confirmed by positive PCR, antigen...

  Summary -- What is already known about this topic? -  Influenza-associated encephalopathy (IAE) is a rare, severe neurologic complication of influenza. -- What is added by this report? - During the high-severity 2024–25 influenza season, 109 U.S. pediatric IAE cases were identified; 55% of affected children were previously healthy . Thirty-seven IAE cases were subcategorized as acute necrotizing encephalopathy (ANE), a severe form of IAE characterized by rapid neurologic decline and a poor prognosis . Overall, 74% of IAE patients were admitted to an intensive care unit , and 19% died ; 41% of ANE patients died. Only 16% of vaccine-eligible IAE patients had received the 2024–25 influenza vaccine. -- What are the implications for public health practice? - All children are at risk for severe neurologic complications of influenza . Annual influenza vaccination is recommended for all children aged ≥6 months to prevent influenza and associated complications, potentially including ...

  Abstract This study compares infant (0–24 months) respiratory infection presentations to a Northern Italian paediatric emergency department across two post-pandemic winters ( 2022–2023 vs 2023–2024 ). Despite an approximate 44% reduction in visits in 2023–2024 (N=176 in 2023–2024 vs N=317 in 2022–2023), infants in the 2023–2024 season experienced significantly higher proportions of ventilatory support (51.1% vs 32.8%, p<0.001) and intensive care unit admission (15.9% vs 1.9%, p<0.001) than those presenting in 2022–2023, with a non-significant trend towards higher hospitalisation (88.1% vs 81.7%, p=0.052). Respiratory syncytial virus re-emerged as the dominant pathogen (43.2% vs 27.7%, p<0.001) in 2023–2024, alongside increased human metapneumovirus and influenza A H1N1 . These findings highlight a concerning shift towards increased severity, underscoring the need for ongoing surveillance. Source: BMJ Paediatric Open,  https://bmjpaedsopen.bmj.com/content/9/1/e003695...

  Abstract Risk of death for both mother and fetus following Ebola virus infection is extremely high . In this study, healthy women in Rwanda aged ≥18 years were randomized to two-dose Ebola vaccination (Ad26.ZEBOV, MVA-BN-Filo) during pregnancy (group A) or postpartum (group B). Unvaccinated pregnant group B women served as control. This was a parallel, randomized, controlled, open-label, single-center trial to evaluate the safety (primary endpoint—outcomes of interest and serious adverse events (SAEs)) and immunogenicity (secondary endpoint) of the two-dose Ebola vaccination. Among 3,484 women screened, 2,013 were randomized, and 2,012 women and 1,945 infants born alive were descriptively analyzed . Adverse outcomes of interest occurred in women ( 5.2% in group A and 7.3% in group B ) and infants ( 26.0% in group A and 25.6% in group B ). The most common maternal outcome of interest was pathways to preterm birth (3.2% in group A and 3.4% in group B), and the most common infant ou...

  Abstract As intrinsic differences in humoral immune response to SARS-CoV-2 between children and adults remain unclear , we improved characterisation by defining the kinetics, specificity and function of antibodies to SARS-CoV-2 in children (n = 146, aged 9.4 ± 4.8 years with n = 257 samples) compared to adults (n = 85, aged 39.5 ± 15.2 years with n = 122 samples). We used plasma samples from an infection and vaccination-naive cohort study with RT-PCR confirmed ancestral B.1* SARS-CoV-2 virus infection with asymptomatic or mild disease, collected in Hong Kong between March to December 2020, from acute (0–14 days post infection) to convalescent (15–206 days) timepoints. Children had significantly lower primary antibody responses against SARS-CoV-2 proteins overall, leading to a less isotype switched response. While children had lower OC43 Spike and SARS-CoV-2 S2 IgG and avidity than adults, they exhibited higher avidities for SARS-CoV-2 whole Spike and Nucleocapsid , and higher lev...

Summary Background The Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology (PREMISE) programme was established to translate knowledge gained from global immunoepidemiological surveillance into a better understanding of population-level dynamics of emerging and re-emerging infections , as well as into the discovery and development of biomedical countermeasures against potential pandemic threats. As proof of principle for this approach, we conducted a longitudinal immunoepidemiological study in children in the USA, focusing on enterovirus D68 (EV-D68) infection dynamics but also capturing surveillance of a broad array of other endemic respiratory pathogens. Serendipitously, our sampling spanned the lifting of widespread COVID-19 non-pharmaceutical interventions (NPIs) in 2022–23, following a unique period during which virus exposure markedly diminished. Methods This prospective, multicentre, longitudinal, immunoepidemiological surveillance study enroll...

Abstract Mycoplasma pneumonia pneumonia(MPP) is a common respiratory disease that often occurs in children . The purpose of this study was to explore the clinical characteristics of children with mycoplasma pneumoniae pneumonia, the first outbreak after the prevalence of COVID-19 epidemic . Meanwhile, this study also analyzed the predictive value of serum protein indicators and coagulation parameters in the MPP group, as well as the correlation between these indicators. Children with Mycoplasma pneumoniae admitted to the pediatric ward of Chengdu Fifth People’s Hospital from May 2023 to March 2024 were selected. After screening, 411 children who met the research criteria were selected as the study subjects. All of the blood samples were tested for coagulation function , procalcitonin, serum protein and glucose among MPP group and control group. All data were processed for statistical analysis using GraphPad Prism 10.2.3. Comparison of the serum proteins and coagulation function between...

Key Points -- Question: What were the clinical characteristics, management approaches, and outcomes among children with influenza-associated acute necrotizing encephalopathy (ANE) in the US during the 2023-2024 and 2024-2025 influenza seasons? -- Findings:   In this multicenter case series of 41 children from 23 US hospitals , influenza-associated ANE carried a 27% mortality rate despite multimodal therapy. Most patients (76%) had no significant medical history , despite 15 of 32 tested (47%) having genetic risk alleles potentially related to risk of ANE identified during diagnostic evaluation. The H1 2009 influenza A strain predominated (34% of cases), and only 16% had received seasonal influenza vaccination . Among survivors, 63% had moderate to severe disability at 90-day follow-up. -- Meaning:  Influenza-associated ANE represents a rare but devastating neurologic complication primarily affecting previously healthy children. The high morbidity and mortality emphasize t...