Human milk oligosaccharides (HMOs) are bioactive components of breast milk with diverse health benefits, including shaping the gut microbiota, modulating the immune system, and protecting against infections. HMOs exhibit dynamic secretion patterns during lactation, influenced by maternal genetics and environmental factors. Their direct and indirect antimicrobial properties have garnered significant research interest. However, a comprehensive understanding of the secretion dynamics of HMOs and their correlation with antimicrobial efficacy remains underexplored.

To synthesize current evidence on the secretion dynamics of HMOs during lactation and evaluate their antimicrobial roles against bacterial, viral, and protozoal pathogens.

A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library focused on studies investigating natural and synthetic HMOs, their secretion dynamics, and antimicrobial properties. Studies involving human, animal, and in vitro models were included. Data on HMO composition, temporal secretion patterns, and mechanisms of antimicrobial action were extracted. Quality assessment was performed using validated tools appropriate for study design.

A total of 44 studies were included, encompassing human, animal, and in vitro research. HMOs exhibited dynamic secretion patterns, with 2'-fucosyllactose (2'-FL) and lacto-N-tetraose peaking in early lactation and declining over time, while 3-fucosyllactose (3-FL) increased during later stages. HMOs demonstrated significant antimicrobial properties through pathogen adhesion inhibition, biofilm disruption, and enzymatic activity impairment. Synthetic HMOs, including bioengineered 2'-FL and 3-FL, were structurally and functionally comparable to natural HMOs, effectively inhibiting pathogens such as Pseudomonas aeruginosa, Escherichia coli, and Campylobacter jejuni. Additionally, HMOs exhibited synergistic effects with antibiotics, enhancing their efficacy against resistant pathogens.

HMOs are vital in antimicrobial defense, supporting infant health by targeting various pathogens. Both natural and synthetic HMOs hold significant potential for therapeutic applications, particularly in infant nutrition and as adjuncts to antibiotics. Further research, including clinical trials, is essential to address gaps in knowledge, validate findings, and explore the broader applicability of HMOs in improving maternal and neonatal health.

While children represented a small percentage of those hospitalized during the COVID-19 pandemic, there was a surge of pediatric viral-related admissions in the immediate postpandemic viral season. Our study compares the epidemiology and health care utilization of children with acute respiratory infections during the 2022-2023 season to prepandemic and subsequent postpandemic seasons to see if trends persisted.

We examined administrative data for children who presented to 2 urban pediatric emergency departments (ED) during 3 periods: 2017-2020 (prepandemic), 2022-2023 (immediate postpandemic), and 2023-2024 (subsequent postpandemic). Outcomes included hospitalization rate for viral-related indications, stepdown/intensive care unit (ICU) admission, and use of advanced respiratory support. Multivariable regression controlled for demographics and specific viruses.

During the study period, there were 65,313 all-cause ED encounters. Compared with prepandemic seasons, viral-related admissions doubled in 2022-2023. In addition to an increase in ED visits, the odds of viral-related admission increased by 98% [adjusted odds ratio (aOR): 1.98; 99.8% CI: 1.75-2.24], odds of stepdown/ICU admission increased by 131% (aOR: 1.31; 99.8% CI: 1.67-3.21) and odds of advanced respiratory support increased by 70% (aOR: 1.70; 99.8% CI: 1.21-2.40). In 2023-2024, the stepdown/ICU admission rate remained the same compared with 2022-2023, and the odds of advanced respiratory support increased (aOR: 1.79, 99.8% CI: 1.22-2.63). Infection with respiratory syncytial virus increased adjusted odds of more advanced care.

Pediatric ED visits and hospitalization rate decreased in 2023-2024 compared with the postpandemic surge, but the admission rate remained high compared with prepandemic seasons, percent admitted to stepdown/ICU persisted, and the use of advanced respiratory support continued to increase.

The evaluation of the spread of respiratory viruses in the context of the COVID-19 pandemic is required to understand how SARS-CoV-2 may have impacted the spectrum of respiratory viruses among children. Our study aimed to examine the viral etiology of respiratory infections other than SARS-CoV-2 in children during the COVID-19 pandemic.

Three databases including PubMed, Scopus, and Web of Science were systematically searched from 2020 to 2023 to assess the pooled prevalence of respiratory viruses in different regions, types of patient care, and types of respiratory disease.

A total of 68 studies were included in this systematic review and meta-analysis. Rhinovirus/Enterovirus (29.1%) and Respiratory syncytial virus (11.3%) were among the most common viruses among children with respiratory infections during the COVID-19 pandemic. In the case of patients younger than 5 years old, Rhinovirus/Enterovirus (36.2%) were the most prevalent viruses among all types of respiratory diseases. Also, Rhinovirus/Enterovirus were the most common viruses in the case of acute respiratory infection (26.1%), upper respiratory tract infection (21.0%), pneumonia (97.3%), and severe acute respiratory infection (54.7%). The most common viruses detected among inpatient cases were Rhinovirus/Enterovirus (47.4%) and Respiratory syncytial virus (14.9%). The prevalence of Influenza A + B viruses and Metapneumovirus among inpatients was also significantly higher than among outpatients.

The high prevalence of viruses such as Rhinovirus/Enterovirus and Respiratory syncytial virus in various respiratory conditions, shows the requirement for enhanced surveillance, vaccination, and treatment strategies. The significance of Influenza viruses and metapneumovirus in inpatient settings delineates the importance of prioritizing them in future preventive measures such as vaccine development to minimize respiratory infection-associated hospitalization.

Decreased severe respiratory illness was observed during the first 2 years of the COVID-19 pandemic, with a relatively smaller decrease among children with medical complexity (CMC) compared to non-CMC. We extended this analysis to the third pandemic year (April 1, 2022, to March 31, 2023) when pandemic public health measures were loosened. A population-based repeated cross-sectional study evaluated respiratory hospitalizations among CMC and non-CMC (<18 years) in Ontario, Canada. Among the 67,517 CMC and 3,006,504 non-CMC in Ontario, there were more CMC respiratory hospitalizations compared with the expected prepandemic levels (n = 3145 hospitalizations, corresponding to rate ratio [RR], 1.20; 95% confidence interval [CI], 1.16-1.25) with an even larger relative increase among non-CMC (n = 6653, RR, 1.36; 95% CI, 1.34-1.38). Increased intensive care unit admissions for respiratory illness were also observed (CMC: RR, 1.44; 95% CI, 1.31-1.59; non-CMC: RR, 2.02; 95% CI, 1.89-2.16). Understanding respiratory surge drivers may provide insights to protect at-risk children from respiratory morbidity.

Though usually self-limiting, viral respiratory infections can escalate to severe cases requiring admission to a pediatric intensive care unit (PICU). This study aims to examine the proportional incidence, affected age ranges, viral pathogens involved, associated severity measures, and the impact of the COVID-19 pandemic on their incidence and virus distribution. This retrospective cohort study conducted in a tertiary care center (2011-2021) reviewed all pediatric patients admitted to PICU with laboratory-confirmed viral respiratory infection. The study included 312 patients, comprising 5.5% of all PICU admissions; 45% were males; 52% had underlying conditions. The median age was 1.1 (IQR 0.3-2.8) years; 18% were born prematurely. The most common viruses were respiratory syncytial virus (35%), adenovirus (26%), influenza (10%), parainfluenza (11%), and human metapneumovirus (11%). All viruses displayed a seasonal pattern, except year-round occurrence in adenovirus. The seasonality pattern was disrupted by COVID-19 pandemic-related restrictions. Mechanical ventilation was required for 46% of patients; 27% required other non-invasive respiratory support. Thirty-day mortality was documented in 18 (5.8%) patients. Underlying conditions, particularly immunosuppression, neuromuscular diseases, and genetic/metabolic syndromes, were associated with increased mortality (p = 0.001, 0.006, and 0.001, respectively). Adenovirus was also linked to higher mortality (p = 0.04), hMPV to prolonged ventilation (p = 0.004) and prolonged PICU stay (p = 0.009), and SARS-CoV-2 to extended ventilation (p = 0.04). During COVID-19, patients were older (p = 0.001), RSV cases decreased (p = 0.006), ventilation duration increased (p = 0.03), and cardiologic complications rose (p = 0.02). No influenza A or B cases appeared post-pandemic.

Viral respiratory infections can lead to severe complications. Their high prevalence in infants and young children highlights the need to extend vaccination age ranges for vaccine-preventable viral infections, monitor uptake in at-risk children, and implement public health interventions in daycare settings.

• Viral respiratory infections in children are a significant cause of illness and mortality.

• Severe infections in children beyond current vaccine eligibility suggest the need to expand vaccination to broader age groups. • SARS-CoV-2 dominance during the COVID-19 pandemic altered disease characteristics of respiratory infections.

To assess factors associated with the risk of severe disease in children aged 5 years or younger with laboratory-confirmed respiratory syncytial virus (RSV) infection.

We conducted a nationwide retrospective cohort study in Mexico.

Eligible participants included children aged 5 years or younger with laboratory-confirmed RSV infection January 1, 2023, and May 15, 2024. We collected relevant clinical and epidemiological data. Risk ratios (RR) and 95% confidence intervals (CI) were employed to identify factors associated with the risk of severe disease, characterized by clinical and radiographic evidence of bronchiolitis or pneumonia requiring hospital admission.

Data from 2022 children were analyzed and the overall risk of severe disease was 21.0% (n = 424/2022). In multiple generalized linear regression analysis, a personal history of immunosuppression (due to any cause) showed a protective effect (RR = 0.14, 95% CI 0.05-0.42, P = 0.001) against severe RSV disease, while an increased risk was documented for each additional day elapsed between the date of symptom onset and the date of seeking healthcare RR = 1.06, 95% CI 1.02-1.10, P = 0.004).

These findings provide insights into risk stratification and suggest specific directions for future research. This information informs the development of targeted intervention strategies to mitigate the impact of RSV infections in this vulnerable population.

To address the research gap in the epidemiology of pediatric respiratory tract infections (RTIs) in Luzhou, Southern Sichuan, China, by analyzing respiratory pathogens in a large pediatric cohort from 2018 to 2021, covering the pre- and during-COVID-19 periods.

This study conducted a retrospective analysis of children with RTIs in Luzhou from July 2018 to January 2021. Strict exclusion criteria were applied to ensure an accurate representation of the pediatric population. Pathogen detection included viruses, bacteria, and atypical agents.

Pathogens were identified in 52.8% of 12,546 cases. Viruses accounted for 32.2% of infections, bacteria for 29.8%, and atypical agents for 29.7%, with significant findings of Staphylococcus aureus, Moraxella catarrhalis, and Mycoplasma pneumoniae. Age-related analysis indicated a higher incidence of bacterial infections in infants and viral infections in preschool-aged children, with atypical pathogens being most prevalent in 3-5-year-olds. Gender-based analysis, adjusted for age, revealed similar overall pathogen presence; however, females were more susceptible to viral infections, while males were more prone to Streptococcus pneumoniae. Notably, there was an unusual increase in pathogen cases during spring, potentially influenced by behavioral changes and public health measures related to COVID-19. Co-infections were identified as a significant risk factor for the development of pneumonia.

The study provides essential insights into the epidemiology of respiratory pathogens in pediatric populations, emphasizing the need for healthcare strategies tailored to age, gender, and seasonality. The findings highlight the impact of environmental and public health factors, including COVID-19 measures, on respiratory pathogen prevalence, underscoring the importance of targeted diagnostic and treatment protocols in pediatric respiratory infections.

While low winter temperatures are associated with increased mortality, this phenomenon has been suggested to be most severe in regions with seemingly mild winters. The study aimed to establish a temperature-based formula that could elucidate the previously ambiguous regional differences in vulnerability to low temperature. European weekly mortality data (2000-2019) were matched with meteorological data to determine for each region vulnerability to temperature decrease and the optimal temperature with lowest mortality. Regression models were developed to generalize and explain these findings considering regional temperature characteristics. Optimal temperature could be predicted based on local average summer temperature (R2 = 85.6%). Regional vulnerability to temperature decrease could be explained by combination of winter and summer temperatures (R2 = 86.1%). Regions with warm winters and cold summers showed the highest vulnerability to decrease of temperature during winter. Contrary to theories about economic disparities Eastern Europe exhibited resistance comparable to Scandinavia. The southern edges of Europe demonstrated serious low temperature vulnerability to decreased temperatures, even if temperature was relatively high around 20 °C. This suggests that the observed connection primarily reflects the modulation of the length of respiratory virus infection seasons by climate conditions, counterbalanced by varying levels of acquired immunity and the presence of heatwaves eliminating the most frail individuals. Thus, relatively low vulnerability and a flat mortality cycle in countries with harsh climates paradoxically imply the presence of threats throughout the whole year.

Respiratory syncytial virus (RSV) is one of the leading causes of hospitalisation, morbidity, and mortality due to respiratory infection in the first years of life. This longitudinal prospective study outlines the 2022/23 season's viral patterns in Austria after the epidemiological changes determined by public health measures. We aimed to highlight differences within the RSV subtypes and genotypes in 0-36-month-old children without chronic diseases in the outpatient setting.

From November 2022 to March 2023 children younger than 36 months admitted to Vienna's largest paediatric primary healthcare centre with an acute respiratory infection were enrolled in this study. Nasal swabs and multiplex PCR panels detected 20 viruses including RSV subtypes and genotypes. Clinical presentation, features, and treatment of the participants were documented and analysed using the Modified Tal Score (MTS). Patients were scheduled for a telemedical follow-up one week after the initial appointment. Analysis was done using descriptive statistics, including Cramér V and binominal logarithmic regression.

Among the 345 samples from 329 children, RSV was the most common virus (31.9%), followed by influenza (17.5%) and rhinovirus infections (20.58%). Of the RSV positive samples, only 13 cases were RSV subtype A (11.8%), whereas 97 were of subtype B (87.3%); ON1 and BA9 were the only detectable RSV genotypes (ON1: BA9 = 1:9.25). RSV was the main predictor of hospitalisation (OR: 7.5, 95% CI: (1.46-38.40), and age had a significant but smaller effect (OR: 0.89, 95% CI: (0.81-0.99). Almost all patients' clinical status improved within the first days.

RSV cases showed a rapid onset in late November 2022, and subtype B was predominant throughout the season. RSV infection was associated with higher hospitalisation rates, even after excluding high-risk patients (preterm and severe chronic diseases population).Further testing in the upcoming winter seasons will improve our knowledge of the dominant subtype and its association with disease severity, especially with the development of novel RSV vaccine candidates.

The US confronted a "triple-demic" of influenza, respiratory syncytial virus (RSV), and COVID-19 in the winter of 2022, leading to increased respiratory infections and a higher demand for medical supplies. It is urgent to analyze these epidemics and their spatial-temporal co-occurrence, identifying hotspots and informing public health strategies.

We employed retrospective and prospective space-time scan statistics to assess the situations of COVID-19, influenza, and RSV in 51 US states from October 2021 to February 2022, and from October 2022 to February 2023, respectively. This enabled monitoring of spatiotemporal variations for each epidemic individually and collectively.

Compared to winter 2021, COVID-19 cases decreased while influenza and RSV infections significantly increased in winter 2022. We found a high-risk cluster of influenza and COVID-19 (not all three) in winter 2021. In late November 2022, a large high-risk cluster of triple-demic emerged in the central US. The number of states at high risk for multiple epidemics increased from 15 in October 2022 to 21 in January 2023.

Our study offers a novel spatiotemporal approach that combines both univariate and multivariate surveillance, as well as retrospective and prospective analyses. This approach offers a more comprehensive and timely understanding of how the co-occurrence of COVID-19, influenza, and RSV impacts various regions within the United States. Our findings assist in tailor-made strategies to mitigate the effects of these respiratory infections.

The COVID-19 pandemic has resulted in the implementation of strict mitigation measures that have impacted the transmission dynamics of human respiratory syncytial virus (HRSV). The measures also have the potential to influence the evolutionary patterns of the virus. In this study, we conducted a comprehensive analysis comparing genomic variations and evolving characteristics of its neutralizing antigens, specifically F and G proteins, before and during the COVID-19 pandemic. Our findings showed that both HRSV A and B exhibited an overall chronological evolutionary pattern. For the sequences obtained during the pandemic period (2019-2022), we observed that the HRSV A distributed in A23 genotype, but formed into three subclusters; whereas the HRSV B sequences were relatively concentrated within genotype B6. Additionally, multiple positively selected sites were detected on F and G proteins but none were located at neutralizing antigenic sites of the F protein. Notably, amino acids within antigenic site III, IV, and V of F protein remained strictly conserved, while some substitutions occurred over time on antigenic site Ø, I, II and VIII; substitution S389P on antigenic site I of HRSV B occurred during the pandemic period with nearly 50% frequency. However, further analysis revealed no substitutions have altered the structural conformations of the antigenic sites, the vial antigenicity has not been changed. We inferred that the intensive public health interventions during the COVID-19 pandemic did not affect the evolutionary mode of HRSV.

Nonpharmacological interventions (NPIs) reduce the incidence of respiratory infections. After NPIs imposed during the coronavirus disease 2019 pandemic ceased, respiratory infections gradually increased worldwide. However, few studies have been conducted on severe respiratory infections requiring hospitalization in pediatric patients. This study compares epidemiological changes in severe respiratory infections during pre-NPI, NPI, and post-NPI periods in order to evaluate the effect of that NPI on severe respiratory infections in children.

We retrospectively studied data collected at 13 Korean sentinel sites from January 2018 to October 2022 that were lodged in the national Severe Acute Respiratory Infections (SARIs) surveillance database.

A total of 9,631 pediatric patients were admitted with SARIs during the pre-NPI period, 579 during the NPI period, and 1,580 during the post-NPI period. During the NPI period, the number of pediatric patients hospitalized with severe respiratory infections decreased dramatically, thus from 72.1 per 1,000 to 6.6 per 1,000. However, after NPIs ceased, the number increased to 22.8 per 1,000. During the post-NPI period, the positive test rate increased to the level noted before the pandemic.

Strict NPIs including school and daycare center closures effectively reduced severe respiratory infections requiring hospitalization of children. However, childcare was severely compromised. To prepare for future respiratory infections, there is a need to develop a social consensus on NPIs that are appropriate for children.

BACKGROUND Respiratory tract infections (RTIs) in children often involve a complex interplay between viruses and bacteria. This study aimed to evaluate clinical presentation in children under 5 years old diagnosed with non-COVID-19 bacterial and viral respiratory tract co-infections between October 2021 and May 2022 in Białystok, Poland. MATERIAL AND METHODS We recruited 100 children under 5 years with RTIs who tested negative for SARS-CoV-2. Nasopharyngeal swabs were screened for 19 viruses and 7 bacterial strains using molecular assays. RESULTS Viral pathogens were detected in 71% of patients and bacterial pathogens were detected in 59%. The most common pathogens were Haemophilus influenzae (n=48), rhinoviruses (n=32), and Streptococcus pneumoniae (n=30). Single pathogens were detected in 36%, dual in 37%, triple in 15%, and quadruple in 2%. Bacterial pathogens were co-detected with viruses in 40 cases, mostly with rhinoviruses (n=15). Two different viruses were found in 14 children and the most common co-detection was adenovirus with rhinovirus (n=5); dyspnea (63% vs 11%) and wheezing (75% vs 22%) were more common in children with human bocavirus. Fever was a common symptom in children with human adenovirus (88% vs 58%). Detection of bacteria and multiple detections were more common in day-care attendees, but were not associated with clinical picture of RTI. CONCLUSIONS Consistent with previous studies, we found a high prevalence of rhinoviruses, despite ongoing implementation of non-pharmaceutical interventions to contain the COVID-19 pandemic. Co-detection of 2 different respiratory pathogens was frequent, but we found no evidence that this was associated with the severity of infections.

In May 2023, the U.S. FDA advisors endorsed Pfizer's pregnancy-administered vaccine (branded ABRYSVO) to protect infants from respiratory syncytial virus (RSV) infection. Vaccination can reduce the burden of RSV-related respiratory disease, with previous studies showing its substantial medical and financial burden in Jordan. However, pregnant women may exhibit hesitancy to get vaccinated due to concerns about potential risks to themselves or their fetuses. This study aimed to assess the acceptance of the RSV vaccine among young females and identify the determinants influencing their decision using a newly constructed instrument. A survey instrument was developed and validated, comprising 26 items to measure RSV vaccine acceptance. A cross-sectional study design was employed, with data collection from a sample of females aged 18 to 45 residing in Jordan during 5-6 July 2023, using a convenient approach via an online distributed questionnaire. The final study sample comprised 315 respondents, with 67.6% who have heard of RSV before the study. If the vaccine was safe, effective, and provided freely, 70.2% showed willingness to get the RSV vaccine, 15.2% resisted, and 14.6% were hesitant. Principal component analysis identified six internally consistent sub-scales with the following suggested themes: Advice, Burden, Conspiracy, Dangers, Efficiency, and Fear, comprising 21 items collectively as assigned as the "ABCDEF" scale for RSV vaccine acceptance. RSV vaccine acceptance in this study was associated with the advice and fear constructs. The validated survey instrument successfully captured important determinants of RSV vaccine acceptance among young females. RSV vaccine promotion efforts should focus on the following: enhancing vaccine education, improving trust in healthcare institutions and providers, reducing burdens through resolving cost issues and focusing on the role of social support, addressing safety concerns, and tailoring communication strategies to effectively promote the benefits of the vaccine. These insights can inform public health policies and interventions aiming to promote RSV vaccination and mitigate the burden of RSV-related diseases among infants. Follow-up studies are recommended with pregnant women as the target group to assess their attitude towards RSV vaccination and to confirm the validity of the conceived ABCDEF survey instrument.

The United States confronted a "triple-demic" of influenza, respiratory syncytial virus, and COVID-19 in the winter of 2022, resulting in increased respiratory infections and a higher demand for medical supplies. It is urgent to analyze each epidemic and their co-occurrence in space and time to identify hotspots and provide insights for public health strategy.

We used retrospective space-time scan statistics to retrospect the situation of COVID-19, influenza, and RSV in 51 US states from October 2021 to February 2022, and then applied prospective space-time scan statistics to monitor spatiotemporal variations of each individual epidemic, respectively and collectively from October 2022 to February 2023.

Our analysis indicated that compared to the winter of 2021, COVID-19 cases decreased while influenza and RSV infections increased significantly during the winter of 2022. We revealed that a twin-demic high-risk cluster of influenza and COVID-19 but no triple-demic clusters emerged during the winter of 2021. We further identified a large high-risk cluster of triple-demic in the central US from late November, with COVID-19, influenza, and RSV having relative risks of 1.14, 1.90, and 1.59, respectively. The number of states at high risk for multiple-demic increased from 15 in October 2022 to 21 in January 2023.

Our study provides a novel spatiotemporal perspective to explore and monitor the transmission patterns of the triple epidemic, which could inform public health authorities' resource allocation to mitigate future outbreaks.