Real-world evidence on nirsevimab impact beyond the first season when given under universal immunisation programmes is emerging. We aimed to assess the medium-term impact of universal infant respirato Show more
Real-world evidence on nirsevimab impact beyond the first season when given under universal immunisation programmes is emerging. We aimed to assess the medium-term impact of universal infant respiratory syncytial virus (RSV) prophylaxis with nirsevimab across inpatient and outpatient settings during two consecutive RSV seasons. NIRSE-GAL is an ongoing, population-based, prospective, longitudinal study in Galicia, Spain. For this study, we included all infants eligible for nirsevimab in the 2023-24 RSV campaign in Galicia, followed up from their first RSV season (2023-24) until the end of their second RSV season (2024-25). The primary endpoint was RSV-related lower respiratory tract infection (LRTI) hospitalisation. Secondary endpoints were LRTI hospitalisation, acute bronchitis or bronchiolitis hospitalisation, pneumonia admissions, all-cause hospitalisations, and primary health-care outcomes (acute bronchitis or bronchiolitis, wheezing or asthma, LRTI, respiratory infections, acute otitis media, and all otitis diagnoses). The first recurrences of these endpoints were also assessed as secondary endpoints. Impact was estimated by Poisson regression models using weekly incidence rates of historical non-pandemic seasons (2017-18 to 2022-23) as comparators, adjusted for RSV seasonality, and evaluated across three follow-up periods: the first RSV season, the second RSV season, and up to 18 months. This study is registered with ClinicalTrials.gov, NCT06180993. Of 12 492 eligible infants, 11 796 received nirsevimab (94·4% coverage). Compared with historical cohorts, RSV-related LRTI hospitalisations decreased by 85·9% (95% CI 80·2-90·0) in the first season and 55·3% (22·5-74·3) in the second, with an estimated 123 infants needing to be immunised to prevent a second-season admission. First LRTI hospitalisations decreased by 59·8% (46·5-69·8) in the first season and 48·1% (33·1-59·7) up to 18 months. Acute bronchitis or bronchiolitis admissions decreased by 59·0% (37·9-72·9) in the first season and 58·7% (40·6-71·3) up to 18 months. All-cause hospitalisation declined by 20·3% (3·1-34·4) in the first season, with no significant reduction thereafter. First recurrent admissions in the second season decreased by 78·2% (25·6-93·6) for RSV-related LRTI, 62·4% (30·9-79·6) for LRTI, and 76·9% (5·3-94·4) for acute bronchitis or bronchiolitis. First outpatient visits declined during the first season by 30·8% (17·5-41·9) for bronchitis or bronchiolitis, 33·4% (21·6-43·4) for LRTI, and 27·7% (14·9-38·5) for wheezing or asthma. First recurrent outpatient visits also declined, by 52·5% (39·7-62·6) for acute bronchitis or bronchiolitis, 28·2% (17·8-37·3) for wheezing or asthma, and 47·3% (35·3-57·2) for LRTI. Universal infant nirsevimab prophylaxis markedly reduced RSV-related hospitalisations and outpatient morbidity, with sustained reductions in RSV-related LRTI hospitalisations into the second season and no signal of adverse shift in RSV morbidity. These findings provide robust population-level evidence that could be valuable for infant immunisation policies and cost-effectiveness models. Sanofi and AstraZeneca. For the Spanish translation of the abstract see Supplementary Materials section. Show less
The interaction between neurexins and neuroligins promotes the formation of functional synaptic structures. Recently, it has been reported that neurexins and neuroligins are proteolytically processed Show more
The interaction between neurexins and neuroligins promotes the formation of functional synaptic structures. Recently, it has been reported that neurexins and neuroligins are proteolytically processed by presenilins at synapses. Based on this interaction and the role of presenilins in familial Alzheimer's disease (AD), we hypothesized that dysfunction of the neuroligin-neurexin pathway might be associated with AD. To explore this hypothesis, we carried out a meta-analysis of five genome-wide association studies (GWAS) comprising 1, 256 SNPs in the NRXN1, NRXN2, NRXN3, and NLGN1 genes (3,009 cases and 3,006 control individuals). We identified a marker in the NRXN3 gene (rs17757879) that showed a consistent protective effect in all GWAS, however, the statistical significance obtained did not resist multiple testing corrections (OR = 0.851, p = 0.002). Nonetheless, gender analysis revealed that this effect was restricted to males. A combined meta-analysis of the former five GWAS together with a replication Spanish sample consisting of 1,785 cases and 1,634 controls confirmed this observation (rs17757879, OR = 0.742, 95% CI = 0.632-0.872, p = 0.00028, final meta-analysis). We conclude that NRXN3 might have a role in susceptibility to AD in males. Show less