Terho Heikkinen

Background: Male sex is a well‐known risk factor for respiratory syncytial virus (RSV) hospitalization in children, but there are no data on potential differences in clinical features between boys and girls hospitalized with RSV infection. Methods: We compared the average population‐based rates of hospitalization and the clinical features of the illness between boys and girls hospitalized with virologically confirmed RSV infection during 2006–2020 at Turku University Hospital, Finland. During this period, testing for RSV was routine in all children admitted with respiratory infections. The comparisons were performed in different age groups of children up to 5 years of age. Results: Among all 1204 children < 5 years of age hospitalized with RSV, the average annual RSV hospitalization rates were 4.0/1000 in boys and 3.3/1000 in girls (incidence rate ratio [IRR] 1.21; 95% CI, 1.07–1.35; p = 0.001). The difference was greatest in children aged 3–23 months, among whom the corresponding rates were 5.4/1000 in boys and 3.6/1000 in girls (IRR, 1.50; 95% CI, 1.25–1.80; p < 0.001). The occurrence of respiratory distress was consistently higher in boys than in girls among children aged 6–17 months. In this group of 233 children, 128 of 141 (90.8%) boys had documented respiratory distress, compared with 70 of 92 (76.1%) girls ( p = 0.002). Conclusions: Except for the first 3 months after birth, boys have a 50% higher risk of RSV hospitalization than girls during the first 2 years of life. In that same age group, boys hospitalized with RSV have also significantly more respiratory distress than girls.

Background: Long-acting monoclonal antibodies (LAmAbs) could dramatically reduce the RSV disease burden in children if implemented using clear, evidence-based recommendations. Methods: The ARMADA Taskforce – an international, multidisciplinary expert panel – undertook a systematic review to develop LAmAbs consensus recommendations for RSV disease prevention in children. Results: The Taskforce recommends LAmAbs for all infants aged <8 months in the absence of maternal RSV vaccination, preterm infants (<37 weeks’ gestational age) aged <12 months, and children <24 months with high-risk conditions. Seasonal LAmAb administration is recommended, although in RSV endemic countries decisions should be made locally concerning administration year-round or with peak RSV incidences. Conclusions: The Taskforce strongly endorses LAmAbs implementation based on their efficacy, effectiveness and public health impact. These recommendations provide a blueprint to inform guidelines worldwide. Wider equitable access to LAmAbs at affordable prices, especially in low- and middle-income countries is needed to reduce the childhood RSV burden.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic disrupted respiratory syncytial virus (RSV) seasonality. To optimize the use and evaluation of RSV infant immunization strategies, monitoring changes in RSV epidemiology is essential. Methods: Hospitalizations for acute respiratory infections (ARIs) and RSV-coded ARI in children <2 years were extracted in 4 European hospitals, according to predefined case definitions (International Classification of Diseases, Tenth Revision codes). Prepandemic RSV seasons (2017–2018 to 2019–2020) were compared to 2021–2022 and 2022–2023. Results: In 2021–2022 and 2022–2023, the peak number of RSV hospitalizations was higher than prepandemic peaks after short periods of RSV circulation, and lower than prepandemic peaks after long periods of RSV circulation. A greater proportion of RSV hospitalizations occurred in children 1 to <2 years in 2021–2022 in the Netherlands (18% vs 9%, P = .04). No increase in age was observed elsewhere. High-risk children represented a greater proportion of RSV hospitalizations during the pandemic. The proportion of pediatric intensive care unit admissions did not increase. Conclusions: A decrease in population immunity has been linked to older age at RSV hospitalization. We did not observe an increase in age in 3 of the 4 participating countries. Broad age categories may have prevented detecting an age shift. Monitoring RSV epidemiology is essential as Europe implements RSV immunization.

Background: The risk of respiratory syncytial virus (RSV) hospitalization is highest during the first months of life, but few studies have assessed the population‐based rates of hospitalization in monthly age groups of infants.Methods: We determined the average population‐based rates of hospitalization with virologically confirmed RSV infections in children ≤15 years of age admitted during the 10‐year period of 2008–2018. Testing for RSV was routine in all children hospitalized with respiratory infections, and all RSV‐positive children admitted at any time during the study period were included in the analyses.Results: The annual population‐based rate of RSV hospitalization was highest in infants 1 month of age (52.0 per 1000 children; 95% CI, 45.2–59.7), followed by infants <1 month of age (34.8 per 1000; 95% CI, 29.2–41.1) and those 2 months of age (32.2 per 1000; 95% CI, 26.9–38.4). In cumulative age groups, the rate of hospitalization was 39.7 per 1000 (95% CI, 36.2–43.4) among infants <3 months of age, 26.8 per 1000 (95% CI, 24.8–29.0) in infants aged <6 months, and 15.8 per 1000 (95% CI, 14.7–17.0) in those <12 months of age.Conclusion: In monthly age groups of infants, the incidence rates of virologically confirmed RSV hospitalization in all infants up to 3 months of age were substantially higher than those reported in earlier studies. These data may be important for improving the estimates of the cost‐effectiveness of various interventions to reduce the burden of RSV in young infants.

Background Respiratory syncytial virus (RSV) infections cause an estimated 22-50 million episodes of acute lower respiratory infections (ALRI) every year in children younger than 5 years. To date, no overall estimate of RSV-associated hospitalisations in children under 5 years has been published for the European Union (EU). Through statistical modelling, we estimated the RSV hospitalisation burden in children under 5 years of age in EU countries and Norway, by age group and country. Methods We collated national RSV-associated hospitalisation estimates calculated using linear regression models in children under 5 years via the RESCEU project for Denmark, England, Finland, Norway, the Netherlands and Scotland during 2006-2018. A systematic literature review was conducted to collect additional estimates. Using the multiple imputation and nearest neighbour matching extrapolation methods, we estimated RSV-associated hospitalisation rates in all EU countries. Results Additional estimates for Spain and France were found in the literature and added to the analysis. We estimated that an average of 245,244 (95%CI 224,688-265,799) hospital admissions with a respiratory infection per year were associated with RSV in children under the age of 5, with most cases occurring among children aged less than 1 year (75%). Infants aged less than 2 months represented the most affected group (71.6 per 1,000 children; 95%CI: 66.6-76.6). The hospitalisation rates varied widely across countries: for example, estimated rates in the 0-2 months age group ranged from 47.4 (37.5-57.3) per 1,000 in the Netherlands to 98.3 (88.5-108.1) per 1,000 in France. Conclusion To our knowledge, this is the first attempt to estimate the overall RSV hospitalisation burden in children under the age of 5 years in the EU. Our findings will help support decisions regarding prevention efforts, and they will also represent an important benchmark to understand changes in the RSV burden following the introduction of RSV immunisation programs in Europe.

Background: Limited long-term data are available on potential changes in the demographics and management of children hospitalized with influenza. Methods: We identified all children ≤15 years old hospitalized with virologically confirmed influenza at Turku University Hospital, Finland, during the 25-year period of July 1993–June 2018. Data on clinical variables, comorbidities and management were retrieved directly from the medical records. Population-based rates of hospitalization were calculated using official annual databases of children living in the hospital catchment area. Results: Between 1993–1998 and 2013–2018, the median age of children increased from 1.3 years to 3.3 years (P < 0.0001). The proportion of children P < 0.0001 for both). The population-based rates of hospitalization decreased by 49% in children 1 year of age (incidence rate ratio, 0.51; 95% confidence interval: 0.27–0.92; P = 0.018) and increased by 194% in children 6–15 years old (incidence rate ratio, 2.94; 95% confidence interval: 1.70–5.32; P < 0.0001). The median duration of hospitalization shortened from 2.0 days (interquartile range [IQR], 1.0–4.0) to 1.0 day (IQR, 1.0–2.0; P < 0.0001). Conclusions: During the 25 years, the median age of hospitalized children increased by 2 years, while the duration of hospitalization shortened.

Background: Oseltamivir treatment is currently the only way of managing influenza in young infants for whom influenza vaccines are not licensed, but little data exist on the effectiveness of the treatment in this age group.Methods: In a prospective study, we enrolled 431 newborn infants and followed them up for 10 months during their first respiratory season (September 2017‐June 2018). During each respiratory illness, we examined the infants and obtained nasopharyngeal specimens for determination of the viral etiology. Infants with influenza were re‐examined at short intervals, and additional nasopharyngeal specimens were obtained at each visit for measuring the viral load. All infants with symptoms P = .0003). For infants with influenza B, the corresponding durations were 110.0 and 173.9 hours, respectively (P = .03). In infants with influenza A, total symptom scores were significantly lower in oseltamivir‐treated infants at all time points between days 3 and 11 after the onset of therapy. In most children with either influenza A or B, viral antigen concentrations declined rapidly within 1‐2 days after the initiation of oseltamivir treatment.Conclusions: Oseltamivir treatment of infants with influenza rapidly decreased the viral load in nasopharyngeal secretions and shortened the duration and severity of symptoms. The clinical effectiveness of oseltamivir appeared to be greater against influenza A than against influenza B infections.

Background: Every year, influenza viruses infect millions of children and cause an enormous burden of disease. Young children are at the highest risk for influenza‐attributable hospitalizations. Nevertheless, most young children are treated as outpatients, and limited data are available on the burden of influenza in these children.Methods: We carried out a prospective cohort study and followed 431 infants born in June‐August 2017 for 10 months from September 1, 2017, to June 30, 2018. The parents filled out daily symptom diaries and were instructed to bring their child for clinical examination at our study clinic each time the child had fever or any signs or symptoms of respiratory tract infection. During each visit, we obtained nasopharyngeal swab specimens for determination of the viral etiology of the illness.Results: A total of 55 episodes of laboratory‐confirmed influenza were diagnosed among the 408 actively participating children, which corresponds to an annual incidence rate of 135/1000 children (95% Cl, 102‐175). Excluding five children with double viral infection, acute otitis media developed as a complication of influenza in 23 (46%) children. One (2%) child with influenza was hospitalized because of febrile convulsion. The effectiveness of influenza vaccination was 48% (95% CI, −29%‐80%).Conclusions: The burden of influenza during the first year of life is heavy in the outpatient setting where most infants with influenza are managed. Effective strategies for the prevention of influenza particularly in infants under 6 months of age are needed to diminish the burden of disease in this age group.

Background: Influenza A viruses are conventionally thought to cause more severe illnesses than B viruses, but few studies with long observation periods have compared the clinical severity of A and B infections in hospitalized children. Methods: We analyzed the clinical presentation, outcomes and management of all children P = 0.80), and lumbar puncture was performed to 16 (5.7%) children with influenza A and 11 (9.8%) children with influenza B ( P = 0.15). Conclusions: The clinical severity of influenza A and B infections is similar in children. For optimal protection against severe influenza illnesses, the use of quadrivalent vaccines containing both lineages of B viruses seems warranted in children.