Purpose The second year of life is gaining increased attention in the era of long-acting RSV immunoprophylaxis. This multicenter study, across pre- and post-COVID seasons, aimed to assess the association between specific key risk-factors and severe RSV-related disease among hospitalized children aged 12–23 months. Methods This retrospective study included children aged 12–23 months hospitalized with RSV across 11 medical-centers (2017–2021). We compared outcomes of prolonged hospitalization (> 3 days) and PICU (Pediatric Intensive Care Unit) admission for children with risk factors (prematurity < 37 weeks, major congenital heart disease (CHD), chronic lung disease of prematurity (CLD) or Down syndrome (DS)) and those without the respective risk factor, adjusting for demographic variables and COVID-19 pandemic admission. Clinical outcomes were also compared between children with ≥ 1 risk factors and those with none. Results Among 1023 children, 228 (22%) had ≥ 1 risk factor: prematurity (n = 183), CLD (n = 28), CHD (n = 45) or DS (n = 20). In multivariable analysis, prematurity with CLD (aOR 4.7,95%CI:1.97–11.22) or without CLD (aOR 2.26, 95%CI:1.54–3.3), CHD (aOR-3.29, 95%CI:1.6–6.77), DS (aOR-4.14, 95%CI:1.26–13.6) and having ≥ 1 risk (aOR-3.55, 95%CI:2.55–4.96) were independently associated with prolonged hospitalization. DS (aOR 6.7, 95%CI:2.1–22.4), CHD (aOR 3.0,95%CI:1.04–8.66) and having ≥ 1 risk factor (aOR-3.58, 95%CI:1.89–6.80) were also associated with PICU admission. Conclusion Children aged 12–23 months with prematurity, CLD, major CHD or DS had significantly higher rates of prolonged RSV hospitalization. Those with ≥ 1 risk factor, and presumably patients with DS and CHD are at highest risk for severe complications. Preventive strategies for these high-risk populations should be considered in their second-year of life. What is Known: • Children with prematurity, congenital heart disease (CHD), chronic lung disease of prematurity (CLD) or Down syndrome (DS) are at increased risk for severe RSV-related illness in the first year of life. • The second year of life is now relevant for long-acting RSV prevention strategies. What is New: • This multicenter study shows that prematurity, CLD, CHD, and DS remain strong predictors of prolonged RSV hospitalization in children aged 12–23 months. • Those with ≥ 1 risk factor, and presumably those with DS and major CHD, faced the highest risk, with increased likelihood of PICU admission.

There are limited data concerning the immunogenicity and reactogenicity of COVID-19 vaccines in children. A total of 110 children, 5–11 years old were vaccinated with two doses (with a 3-week interval between doses) of the Pfizer-BioNTech COVID-19 vaccine and were followed for 21, 90, and 180 days after vaccination for immunogenicity, adverse events, and breakthrough infections. Ninety days after the first vaccine dose, the GeoMean (CI 95%) of IgG ascended to 1291.0 BAU (929.6–1790.2) for uninfected children and 1670.0 BAU (1131.0–2466.0) for Infected children. One hundred and eighty days after receiving the first dose of the vaccine, the titers decreased to 535.5 BAU (288.4–993.6) for the uninfected children, while only a small decline was detected among infected children—1479.0 (878.2–2490.0). The neutralizing antibodies titer almost did not change over time in the uninfected children, and even elevated for the infected children. Of the 110 vaccinated children, 75.5% were infected, with only mild COVID-19 infection symptoms. Child vaccination was found to be safe, with mild, mostly local, and of short duration, reported AEs. No serious adverse events (SAEs) were reported after vaccination. The durability of two doses of vaccine in children is longer, thus a booster may not be needed as early as in adults.

Community surveillance found the 2019–2020 A(H1N1)pdm09 predominant influenza season in Israel to be a high‐intensity season with an early and steep morbidity peak. To further characterize disease severity in the 2019–2020 season, we analyzed a cohort of hospitalized patients with laboratory‐confirmed influenza from this season (n = 636). Quantitative polymerase chain reaction was performed on clinical samples to detect the presence of influenza. Demographic, clinical, and laboratory data were retrieved via electronic health records and MDClone. Electronic health records were accessed to obtain data on intensive care unit patients, missing data and for data verification purposes. Univariate analysis was performed to compare demographic, comorbidity, and clinical characteristics across the three influenza strains. The A(H1N1)pdm09 predominant 2019–2020 influenza season in Israel was characterized by an early and steep morbidity peak, vaccine delays and shortages, and with the A(H3N2) and B/Victoria strains disproportionately targeting children and young adults, most probably due to reduced immunity to these strains. A greater proportion of children <5 years infected with A(H3N2) and B/Victoria developed severe influenza compared with those infected with A(H1N1)pdm09. Our study emphasizes the vulnerability of infants and young children in the face of rapidly evolving influenza strains and underscores the importance of influenza prevention measures in this population.

Coronavirus disease-associated central nervous system complications (CNS-C) in hospitalized children, especially during the Omicron wave, and in comparison with influenza associated CNS-C, are not well understood. The study population included 755 children aged <18 years hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Sheba Medical Center, during March 2020 to July 2022. A comparative cohort consisted of 314 pediatric patients with influenza during the 2018-2019 and 2019-2020 influenza seasons. Overall, 5.8% (n = 44) of patients exhibited CNS-C. Seizures at presentation occurred in 33 patients with COVID-19 (4.4%), with 2.6% (n = 20) experiencing nonfebrile seizures, 1.1% (n = 8) febrile seizures, and 0.7% (n = 5) status epilepticus. More patients with CNS-C experienced seizures during the Omicron wave versus the pre-Omicron period (77.8% vs 41.2%, P = 0.03). Fewer patients were admitted to the intensive care unit in the Omicron wave (7.4%) versus prior waves (7.4% vs 41.2%, P = 0.02). Fewer patients with SARS-CoV-2 experienced CNS-C (5.8%) versus patients with influenza (9.9%), P = 0.03. More patients with SARS-CoV-2 experienced nonfebrile seizures (2.6% vs 0.6%, P = 0.06), whereas more patients with influenza experienced febrile seizures (7.3% vs 1.1%, P < 0.01). The Omicron wave was characterized by more seizures and fewer intensive-care-unit admissions than previous waves. Pediatric patients with SARS-CoV-2 experienced fewer CNS-C and more nonfebrile seizures compared with patients with influenza.

Background/Objectives: During the 2025–26 influenza season, the antigenically distinct A(H3N2) subclade K emerged and spread globally, raising significant concerns regarding seasonal vaccine effectiveness. This study aimed to map antigenic and structural divergence of this novel strain compared to the 2025/26 A(H3N2) vaccine component. Furthermore, we investigated how this vaccine mismatch impacts functional humoral immunity by directly comparing antibody neutralization profiles between individuals with vaccine-induced protection and those with infection-acquired immunity. Methods: Phylogenetic and structural modeling analyses were performed on 2025–26 Israeli influenza samples to identify genetic distances and mutations in the hemagglutinin protein compared to the 2025/26 A(H3N2) vaccine component. Hemagglutination inhibition (HI) and microneutralization assays were conducted using 2025–26 winter serum samples from a cohort of vaccinated healthcare workers and vaccinated convalescents to quantify antibody responses against both vaccine-like and subclade K strains. Results: Phylogenetic analysis revealed a clear dominance of the subclade K strain in Israel during the winter of 2025–26. Significant vaccine mismatch was defined by eight newly identified hemagglutinin mutations in the circulating subclade K strains. Serological testing demonstrated that while vaccination alone produced a modest two-to-three-fold increase in antibody titers, baseline protection against subclade K remained critically low. Conversely, natural infection in vaccinated convalescents elicited a significantly stronger, broader immune response, demonstrating a 6-fold and 13-fold increase in neutralizing antibodies against the vaccine-like and subclade K strains, respectively. Conclusions: Natural infection provides a more pronounced increase in both binding and neutralizing antibodies compared to vaccination alone, which might contribute to broader cross-protection against antigenically drifted variants. These findings highlight the primary limitations of current influenza strain prediction and emphasize the urgent need for faster, more adaptable vaccine manufacturing platforms to better match actual circulating strains.

Candida species are the leading cause of invasive fungal infections in children and are associated with substantial morbidity and mortality. We conducted a multicenter retrospective study across nine hospitals in Israel, including all candidemia episodes in patients aged 0–18 years between 2010 and 2022. Clinical, microbiological, and outcome data were collected, and multivariable logistic regression was used to identify predictors of 30-day mortality. A total of 498 candidemia episodes were identified in 482 patients. Most episodes occurred in immunocompromised children or those admitted to intensive care units. Non-albicans Candida species predominated (63.3%), although C. albicans remained the single most common species (36.7%). The most frequent non-albicans species were C. parapsilosis (25.5%), C. tropicalis (15.9%), and C. glabrata (9.6%). No cases of C. auris were identified. Fluconazole non-susceptibility was observed in 19.4% of isolates and increased from 15.5% during 2010–2016 to 23.3% during 2017–2022 (OR 2.89, 95% CI 1.45–5.11, p = 0.007). The 30-day mortality rate was 23.4%. Independent predictors of mortality included liver disease, neutropenia, total parenteral nutrition, urinary tract infection, skin lesions, and peritonitis. Pediatric candidemia remains associated with considerable mortality, while increasing fluconazole non-susceptibility among non-albicans Candida species highlights the need for ongoing surveillance and antifungal stewardship.