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Introduction Acute bronchiolitis is the main cause of hospitalization in children under 2 years of age, with a regular seasonality, mostly due to the respiratory syncytial virus. Objectives To describe the epidemiology of bronchiolitis hospitalizations in our center in the last 12 years, and analyze the changes in clinical characteristics, microbiology, and adverse outcomes during the SARS‐CoV‐2 pandemic. Methods Observational study including patients admitted for bronchiolitis between April 2010 and December 2021 in a Spanish tertiary paediatric hospital. Relevant demographic, clinical, microbiological, and adverse outcome variables were collected in an anonymized database. The pandemic period (April 2020 to December 2021) was compared to 2010−2015 seasons using appropriate statistical tests. Results There were 2138 bronchiolitis admissions, with a mean of 195.6 per year between 2010 and 2019 and a 2−4‐month peak between November and March. In the expected season of 2020, there was a 94.4% reduction of bronchiolitis hospitalizations, with only 11 cases admitted in the first year of the pandemic. Bronchiolitis cases increased from the summer of 2021 during a 6‐month long peak, reaching a total of 171 cases. Length of stay was significantly shorter during the pandemic, but no differences were found in clinical and microbiological characteristics or other adverse outcomes. Conclusions The SARS‐CoV‐2 pandemic has modified the seasonality of bronchiolitis hospitalizations, with a dramatic decrease in cases during the expected season of 2020−2021, and an extemporaneous summer−autumn peak in 2021 with longer duration but similar patient characteristics and risk factors.

Purpose STAT1 gain-of-function (GOF) and dominant-negative (DN) STAT3 syndromes share clinical manifestations including infectious and inflammatory manifestations. Targeted treatment with Janus-kinase (JAK) inhibitors shows promising results in treating STAT1 GOF-associated symptoms while management of DN STAT3 patients has been largely supportive. We here assessed the impact of ruxolitinib on the JAK-STAT1/3 pathway in DN STAT3 patients' cells. Methods Using flow cytometry, immunoblot, qPCR, and ELISA techniques, we examined the levels of basal STAT1 and phosphorylated STAT1 (pSTAT1) of cells obtained from DN STAT3, STAT1 GOF patients, and healthy donors following stimulation with type I/II interferons (IFNs) or interleukin (IL)-6. We also describe the impact of ruxolitinib on cytokineinduced STAT1 signaling in these patients. Results DN STAT3 and STAT1 GOF resulted in a similar phenotype characterized by increased STAT1 and pSTAT1 levels in response to IFNα (CD3 + cells) and IFNγ (CD14 + monocytes). STAT1-downstream gene expression and C-X-C motif chemokine 10 secretion were higher in most DN STAT3 patients upon stimulation compared to healthy controls. Ex vivo treatment with the JAK1/2-inhibitor ruxolitinib reduced cytokine responsiveness and normalized STAT1 phosphorylation in DN STAT3 and STAT1 GOF patient' cells. In addition, ex vivo treatment was effective in modulating STAT1 downstream signaling in DN STAT3 patients. Conclusion In the absence of effective targeted treatment options for AD-HIES at present, modulation of the JAK/STAT1 pathway with JAK inhibitors may be further explored particularly in those AD-HIES patients with autoimmune and/or autoinflammatory manifestations.