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RSV hospitalization epidemiology is subject to rapid changes brought about by the COVID-19 pandemic and the prospect of vaccine prevention. The purpose of this report is to characterize recent epidemiologic and clinical fluctuations and to analyze their potential impact on an immunization program with nirsevimab. This is a 2018-2024 retrospective analysis of all hospitalizations caused by RSV in patients below 16 years of age occurring at an academic Children's Hospital that serves a defined population. We simulated the vaccine impact against RSV hospitalization by applying the expected effects of the infant immunization program with nirsevimab proposed in Switzerland to observed case counts. We analyzed 1339 hospitalizations. The consecutive occurrence of two major epidemics in 2022-2023 and 2023-2024 had never been recorded previously. The 2023-2024 season witnessed a major shift to older age. Only 61% of patients were below 12 months of age, while prepandemic long-term surveillance since 1997 found a range between 64 and 85% (median, 73%). Age below 3 months, prematurity, airway anomalies, congenital heart disease, and neuromuscular disorders were independently associated with ICU admission. Simulation of the vaccine impact using two scenarios of coverage and efficacy (scenario 1, 50% and 62%, respectively; scenario 2, 90% and 90%) and three different age distributions resulted in an infant vaccine impact of 31.0% (scenario 1) and 81.0% (scenario 2), respectively. Vaccine impact for all patients below 16 years ranged from 22.7 to 24.9% (scenario 1) and 54.2 to 68.8% (scenario 2)., Conclusion: RSV hospitalization epidemiology was characterized by substantial variability in patient age on admission. As the proposed RSV immunization program primarily targets infants, year-to-year fluctuation of cases among older children will cause a variability of vaccine impact of approximately 15%. This information may be useful for physicians and hospital administrators when they anticipate the resources needed during the winter season., What Is Known: • RSV hospitalization epidemiology was subject to massive disturbances during the COVID-19 pandemic. • Extended half-life monoclonal antibodies and active maternal immunization offer new means of passive protection of infants against severe RSV disease., What Is New: • We demonstrate substantial year-to-year fluctuation of the age distribution at the time of RSV hospitalization. • Up to 40% of annual RSV hospitalizations in a given season occur in children above 12 months of age who do not benefit from maternal RSV immunization and may not be eligible for receipt of a monoclonal antibody., (© 2024. The Author(s).)

Background: To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections., Methods: Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39)., Results: In the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1, VPS37C, TGFB1, MX2, and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%-98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%-97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV., Conclusions: MIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

Purpose: There are limited data on SARS-CoV-2 (COVID-19) infection in children with cancer or after haematopoietic stem cell transplant (HSCT). We describe the severity and outcomes of SARS-COV-2 in these patients and identify factors associated with severe disease., Methods: This was a multinational, observational study of children (aged <19 years) with cancer or HSCT and SARS-CoV-2 confirmed by polymerase chain reaction. COVID-19 was classified as asymptomatic, mild, moderate, severe or critical (≥1 organ support). Exact polytomous regression was used to determine the relationship between clinical variables and disease severity., Results: One hundred and thirty-one patients with COVID-19 across 10 countries were identified (median age 8 years). Seventy-eight (60%) had leukaemia/lymphoma, 48 (37%) had solid tumour and five had primary immunodeficiency and HSCT. Fever (71%), cough (47%) and coryza (29%) were the most frequent symptoms. The median duration of detectable virus was 16 days (range, 1-79 days). Forty-nine patients (37%) were hospitalised for COVID-19 symptoms, and 15 (11%) required intensive care unit-level care. Chemotherapy was delayed/modified in 35% of patients. COVID-19 was asymptomatic in 32% of patients, mild in 47%, moderate in 8%, severe in 4% and critical in 9%. In 124 patients (95%), a full recovery was documented, and four (3%) died due to COVID-19. Any comorbidity (odds ratio, 2.94; 95% confidence interval [CI], 1.81-5.21), any coinfection (1.74; 95% CI 1.03-3.03) and severe baseline neutropenia (1.82; 95% CI 1.13-3.09) were independently and significantly associated with increasing disease severity., Conclusion: Although most children with cancer had asymptomatic/mild disease, 13% had severe COVID-19 and 3% died. Comorbidity, coinfection and neutropenia may increase the risk of severe disease. Our data may help management decisions in this vulnerable population., Competing Interests: Conflict of interest statement A.H.G. has research support from Gilead Sciences, Merck Sharp and Dohme and Pfizer; is a consultant for Amplyx, Astellas, Basilea, F2G, Gilead Sciences, Merck Sharp and Dohme and Pfizer; and served at the speakers' bureau of Astellas, Basilea, F2G, Gilead Sciences, Merck Sharp and Dohme and Pfizer. A.A. is a consultant for Jazz Pharmaceuticals, Amgen, Novartis, Gilead Sciences and MSD/Merck and served at the speakers' bureau of Jazz Pharmaceuticals, Amgen and Novartis. T.L. has an unrestricted research support from Gilead Sciences; is a consultant for Gilead Sciences, Merck Sharp and Dohme, Pfizer, Astellas and Roche; and serves at the speakers' bureau of Gilead Sciences, Merck Sharp and Dohme, Astellas, Pfizer and GlaxoSmithKline. All the other authors do not have to declare a conflict of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In anticipation of an interseasonal respiratory syncytial virus (RSV) epidemic, a clinician-led reporting system was rapidly established to capture RSV infections in Swiss hospitals, starting in January 2021. Here, we present details of the reporting system and first results to June 2021. An unusual epidemiology was observed with an interseasonal surge of RSV infections associated with COVID-19-related non-pharmacological interventions. These data allowed real-time adjustment of RSV prophylaxis guidelines and consequently underscore the need for and continuation of systematic nationwide RSV surveillance.