Non-Pharmacological Interventions During SARS-CoV-2 Pandemic: Effects on Pediatric Viral Respiratory Infections.

INTRODUCTION: Viral lower respiratory tract infections frequently cause morbidity and mortality in children. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic led to isolation and hygiene measures, resulting in decreased respiratory virus transmission and pediatric admissions. This study aimed to assess the impact of these measures and their uplifting on respiratory virus circulation in children before and during the SARS-CoV-2 pandemic (January 2017-December 2022). METHODS: We conducted a weekly time series analysis of multiple virus molecular assays in children. This included those admitted to a university reference hospital's Pediatric Intensive Care Unit (PICU) and those with risk pathologies exhibiting fever and/or respiratory symptoms. We included patients aged 0-18 years residing in Catalonia and adjusted the positive results to account for diagnostic effort. RESULTS: We performed a total of 2991 respiratory virus tests during the period. Confinement significantly decreased the detection of all viruses, especially Rhinovirus (RV). After the deconfinement of children, the viral detection trend remained stable for all viruses, with no short-term impact on virus transmission. The mandatory implementation of facemasks in those aged ≥6 years led to decreased viral circulation, but we observed an influenza virus rebound after facemask removal. At that time, we also noticed an interrupted drop in the detection rates of RV and respiratory syncytial virus (RSV). The reopening of schools led to a progressive increase in viral detections, especially of Rhinovirus. CONCLUSION: Non-pharmacological interventions significantly impact the circulation of respiratory viruses among children. We observed these effects even when some measures did not specifically target preschool-aged children.

Nirsevimab immunization's real-world effectiveness in preventing severe bronchiolitis: A test-negative case-control study.

BACKGROUND: Several clinical trials have shown that nirsevimab, an antibody targeting the respiratory syncytial virus (RSV), reduces RSV bronchiolitis requiring admission. In 2023-2024, Catalonia and Andorra adopted immunization strategies for children <6 months and those born during the epidemic season. This study evaluates the effectiveness of nirsevimab in preventing hospitalizations from RSV bronchiolitis. METHODS: In the epidemic season of 2023-2024, a test-negative case-control study was conducted in three hospitals from Catalonia and Andorra. Patients <12 months old admitted with bronchiolitis and tested for RSV using molecular microbiology tests were included. The effectiveness in preventing RSV bronchiolitis hospitalization and severe disease was estimated using multivariate models. Comparisons between immunized, non-immunized, and non-eligible patients were made in prospectively collected epidemiological, clinical, and microbiological variables. RESULTS: Two hundred thirty-four patients were included. RSV was detected in 141/234 (60.2%), being less common in the immunized group (37% vs 75%, p < .001). The rate of immunized patients among those eligible was 59.7%. The estimated effectiveness for RSV-associated lower respiratory tract infection was 81.0% (95% confidence interval: 60.9-90.7), and for preventing severe disease (the need for NIV/CMV), 85.6% (41.7-96.4%). No significant differences by immunization status were observed in patients with RSV concerning viral coinfections, the need for NIV/CMV or length of hospital stay. CONCLUSIONS: This study provides real-world evidence of the effectiveness of nirsevimab in preventing RSV-lower respiratory tract infection hospitalization and severe disease in infants during their first RSV season following a systematic immunization program. Immunized patients did not exhibit a higher rate of viral coinfections nor differences in clinical severity once admitted.

Impact of universal immunization program with monoclonal antibody nirsevimab on reducing the burden of serious bronchiolitis that need pediatric intensive care.

RSV bronchiolitis remains the leading cause of hospitalization in children under 1 year of age. It is estimated that 2-6% of cases will be hospitalized on pediatric intensive care units (PICUs). In October 2023, a universal immunization program with the monoclonal antibody nirsevimab was implemented in Catalonia. The aim of the study was to analyze the impact of the nirsevimab immunization on the burden of bronchiolitis admitted to a PICU and resulting changes in epidemiological, clinical, and microbiological characteristics comparing the pre-nirsevimab (pre-N) with the post-nirsevimab (post-N) period. This was a prospective, descriptive, and observational study. Patients with severe bronchiolitis admitted to reference children's hospital PICU, between September 2010 and February 2024 were included. Demographic and clinical data were collected and viral laboratory etiological diagnosis was carried out. 1531 patients were recruited, 1458 in the pre-N seasons and 73 after its introduction (58% males, median age 52 days), of which 67% were immunized with nirsevimab. The total number of PICU bronchiolitis admissions, the ratio, and the RSV etiology were significantly lower in the post-N period (p = 0.03, p < 0.001, and p = 0.039, respectively). Significant higher age at admission (p < 0.001) and lower hospital length of stay (p < 0.001) was observed comparing pre-N vs. post-N period. CONCLUSION: Nirsevimab appears to have an important impact on reducing the number and length of stay of PICU admissions due to RSV bronchiolitis. WHAT IS KNOWN: • Bronchiolitis is the most common viral infection of the lower respiratory tract in infants. • It represents 13% of the total pediatric intensive care admissions, typically during winter. This is one of the causes that produces a collapse in the health care systems all around the world. WHAT IS NEW: • In October 2023, universal immunization with monoclonal antibody nirsevimab of all children under 6 months of age was started in the majority of autonomous communities in Spain. • Recent publications from the nirsevimab clinical trials have evidenced a high RSV protective effect, but data on its effect on real life patients who require pediatric intensive care unit admission are missing.

Hybrid capture shotgun sequencing detected unexpected viruses in the cerebrospinal fluid of children with acute meningitis and encephalitis.

PURPOSE: Investigation of undiagnosed cases of infectious neurological diseases, especially in the paediatric population, remains a challenge. This study aimed to enhance understanding of viruses in CSF from children with clinically diagnosed meningitis and/or encephalitis (M/ME) of unknown aetiology using shotgun sequencing enhanced by hybrid capture (HCSS). METHODS: A single-centre prospective study was conducted at Sant Joan de Déu University Hospital, Barcelona, involving 40 M/ME episodes of unknown aetiology, recruited from May 2021 to July 2022. All participants had previously tested negative with the FilmArray Meningitis/Encephalitis Panel. HCSS was used to detect viral nucleic acid in the patients' CSF. Sequencing was performed on Illumina NovaSeq platform. Raw sequence data were analysed using CZ ID metagenomics and PikaVirus bioinformatics pipelines. RESULTS: Forty episodes of M/ME of unknown aetiology in 39 children were analysed by HCSS. A significant viral detection in 30 CSF samples was obtained, including six parechovirus A, three enterovirus ACD, four polyomavirus 5, three HHV-7, two BKV, one HSV-1, one VZV, two CMV, one EBV, one influenza A virus, one rhinovirus, and 13 HERV-K113 detections. Of these, one sample with BKV, three with HHV-7, one with EBV, and all HERV-K113 were confirmed by specific PCR. The requirement for Intensive Care Unit admission was associated with HCSS detections. CONCLUSION: This study highlights HCSS as a powerful tool for the investigation of undiagnosed cases of M/ME. Data generated must be carefully analysed and reasonable precautions must be taken before establishing association of clinical features with unexpected or novel virus findings.