All-cause and pathogen-specific lower respiratory tract infection hospital admissions in children younger than 5 years during the COVID-19 pandemic (2020–22) compared with the pre-pandemic period (2015–19) in South Africa: an observational study

Effectiveness and impact of universal prophylaxis with nirsevimab in infants against hospitalisation for respiratory syncytial virus in Galicia, Spain: initial results of a population-based longitudinal study

The aim of this study was to assess the impact of universal nirsevimab administration on hospitalisations and paediatric intensive care unit (PICU) admissions due to lower respiratory tract infection associated with respiratory syncytial virus (RSV-LRTI). An observational study was conducted at a tertiary hospital in Spain to compare the frequency and characteristics of children under five years of age hospitalised for RSV-LRTI between October 2023 and March 2024 (nirsevimab period), with the data from two prepandemic COVID- 19 seasons (2018–2019 and 2019–2020) and one postpandemic season (2022–2023). A total of 311 patients were included in the study. During the nirsevimab period, a decrease in the number of children hospitalised for RSV-LRTI was observed, particularly for children under six months of age. Compared with the prepandemic period, there was an 83.3% decrease in hospitalisations and a 73.3% reduction in PICU admissions in this age group. Similarly, compared with the postpandemic period, there was a 90.8% reduction in hospitalisations and an 87.9% reduction in PICU admissions. Furthermore, the median age was greater (15.6 months; IQR 11.1–27.3) than it was in the prepandemic period (4 months; IQR 1.6–8.9) and postpandemic period (3.4 months; IQR 1.5–10.6) (p < 0.001). Moreover, the length of hospital stay during the nirsevimab period (4 days; IQR 3–6) was shorter than that observed during the prepandemic period (6 days; IQR 4–9) and the postpandemic period (5 days; IQR 3–8) (p = 0.003).Conclusions: Following the introduction of universal immunoprophylaxis with nirsevimab, notable reductions in hospitalisations and PICU admissions due to RSV-LRTI were observed among young infants. This resulted in a shift in the age profile and a shorter length of hospital stay.What Is Known• Nirsevimab is a novel humanised IgG1 monoclonal antibody with a prolonged half-life that has been demonstrated to reduce RSV-associated hospitalisations in controlled clinical trials; however, real-world data are still limited.What Is New:• The findings of the present study corroborate the effectiveness of nirsevimab. Following the implementation of universal immunoprophylaxis with nirsevimab, a notable reduction in hospitalisations and admissions to the paediatric intensive care unit for RSV-associated lower respiratory tract infections was observed, particularly among infants younger than 6 months, who have been the main target of this passive immunisation strategy. In addition, the patients admitted were older and the length of hospital stay was shorter.

BackgroundThis study aimed to describe the temporal trends in the age and sex burdens of lower respiratory infections (LRIs) in China and globally from 1990 to 2021 and to analyze their epidemiological characteristics to formulate corresponding strategies to control LRIs.MethodsThis study utilized open data from the Global Burden of Disease (GBD) database from 1990 to 2021 to assess the burden of disease based on the prevalence, incidence, mortality, years lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) of LRIs in China and globally. Moreover, a comprehensive comparative analysis of the epidemiological characteristics of LRIs in China and globally was conducted via the Joinpoint regression model, age-period-cohort model (APC model), and stratified analysis of the study method from multiple dimensions, such as age, sex, and period. Finally, we used an autoregressive integrated moving average (ARIMA) model to predict the disease burden in LRIs over the next 15 years.ResultsFrom 1990 to 2021, China's age-standardized incidence, deaths, and disability-adjusted life year (DALY) rates per 100,000 people decreased from 5,481.13 (95% CI: 5,149.05, 5,836.35) to 2,853.81 (95% CI: 2,663.94, 3,067.55), from 60.65 (95% CI. 52.96, 66.66) to 14.03 (95% CI: 11.68, 17) and from 3,128.39 (95% CI: 2,724.11, 3,579.57) to 347.67 (95% CI: 301.28, 402.94). The global age-standardized incidence, deaths, and DALY rates per 100,000 people, on the other hand, decreased from 6,373.17 (95% CI: 5,993.51, 6,746.04) to 4,283.61 (95% CI: 4,057.03, 4,524.89) and from 61.81 (95% CI: 56.66, 66.74) to 28.67 (95% CI: 25.92, 31.07) and from 3,472.9 (95% CI: 3,090.71, 3,872.11) to 1,168.8 (95% CI: 1,016.96, 1,336.95). The decline in the aforementioned indicators is greater in the female population than in the male population, and the decrease in China is more pronounced than the global trend. In China, the age-standardized incidence and mortality rates of LRIs showed an annual average percentage change (AAPC) of −2.12 (95% CI: −2.20, −2.03) and −4.77 (95% CI: −5.14, −4.39), respectively. Globally, the age-standardized incidence and mortality rates for LRIs decreased by −1.28 (95% CI: −1.37, −1.18) and −2.47 (95% CI: −2.61, −2.32). By 2036, the incidence of lower respiratory infections (LRI) among men and women in China is projected to decrease by 36.55 and 46.87%, respectively, while the mortality rates are expected to decline to 12.67% for men and increase by 71.85% for women. In comparison, the global decline in LRI incidence is lower than that observed in China, yet the reduction in mortality rates is greater globally than in China.ConclusionsAge-standardized incidence, mortality and disability-adjusted life years (DALYs) decreased more in China than at the global level between 1990 and 2021. Compared with the previous period, the COVID-19 pandemic has led to a significant decrease in the disease burden of LRIs. As the population continues to age, the disease burden of LRIs in the old adult population will become a major new public health challenge.

BackgroundThe safety of the monoclonal antibody nirsevimab and the effect of nirsevimab on hospitalizations for respiratory syncytial virus (RSV)–associated lower respiratory tract infection when administered in healthy infants are unclear.MethodsIn a pragmatic trial, we randomly assigned, in a 1:1 ratio, infants who were 12 months of age or younger, had been born at a gestational age of at least 29 weeks, and were entering their first RSV season in France, Germany, or the United Kingdom to receive either a single intramuscular injection of nirsevimab or standard care (no intervention) before or during the RSV season. The primary end point was hospitalization for RSV-associated lower respiratory tract infection, defined as hospital admission and an RSV-positive test result. A key secondary end point was very severe RSV-associated lower respiratory tract infection, defined as hospitalization for RSV-associated lower respiratory tract infection with an oxygen saturation of less than 90% and the need for supplemental oxygen.ResultsA total of 8058 infants were randomly assigned to receive nirsevimab (4037 infants) or standard care (4021 infants). Eleven infants (0.3%) in the nirsevimab group and 60 (1.5%) in the standard-care group were hospitalized for RSV-associated lower respiratory tract infection, which corresponded to a nirsevimab efficacy of 83.2% (95% confidence interval [CI], 67.8 to 92.0; P<0.001). Very severe RSV-associated lower respiratory tract infection occurred in 5 infants (0.1%) in the nirsevimab group and in 19 (0.5%) in the standard-care group, which represented a nirsevimab efficacy of 75.7% (95% CI, 32.8 to 92.9; P=0.004). The efficacy of nirsevimab against hospitalization for RSV-associated lower respiratory tract infection was 89.6% (adjusted 95% CI, 58.8 to 98.7; multiplicity-adjusted P<0.001) in France, 74.2% (adjusted 95% CI, 27.9 to 92.5; multiplicity-adjusted P=0.006) in Germany, and 83.4% (adjusted 95% CI, 34.3 to 97.6; multiplicity-adjusted P=0.003) in the United Kingdom. Treatment-related adverse events occurred in 86 infants (2.1%) in the nirsevimab group.ConclusionsNirsevimab protected infants against hospitalization for RSV-associated lower respiratory tract infection and against very severe RSV-associated lower respiratory tract infection in conditions that approximated real-world settings. (Funded by Sanofi and AstraZeneca; HARMONIE ClinicalTrials.gov number, NCT05437510).

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection and hospitalisations in infants worldwide. The primary analyses of HARMONIE showed that nirsevimab reduced infant hospitalisations due to RSV-associated lower respiratory tract infection through the RSV season. This analysis aims to evaluate nirsevimab's efficacy at 180 days after dosing, a period exceeding the typical 5-month RSV season. HARMONIE is an ongoing, open-label, parallel arm, randomised, controlled, phase 3b study conducted in France, Germany, and the UK. Infants aged 12 months or younger, born at a gestational age of at least 29 weeks, were randomly assigned (1:1) to receive either a single intramuscular dose of nirsevimab (50 mg for children <5 kg or 100 mg for children ≥5 kg) or standard care (without RSV prophylaxis) before or during their first RSV season. Randomisation was electronically done, stratified by country and age-group. The primary efficacy endpoint for this analysis was the incidence of hospitalisations due to RSV-associated lower respiratory tract infection up to 180 days after nirsevimab administration or randomisation in all randomised participants. Safety up to 365 days following nirsevimab administration was also assessed. This trial is ongoing and registered with ClinicalTrials.gov, number NCT05437510. Between Aug 8, 2022, and Feb 28, 2023, 8057 infants were randomly assigned to either the nirsevimab group (n=4038) or the standard care group (n=4019). The median age at randomisation was 4·00 months (IQR 1·0-7·0; range 0·0-12·0, and 4195 (52·1%) were male and 3862 (47·9%) were female. Up to 180 days, 12 (0·3%) of 4038 infants in the nirsevimab group and 68 (1·7%) of 4019 infants in the standard care group had been hospitalised for RSV-associated lower respiratory tract infection, corresponding to a nirsevimab efficacy of 82·7% (95% CI 67·8-91·5; p<0·0001). Most participants experienced grade 1 (2759 [68·7%] of 4016 in the nirsevimab group; 2696 [67·1%] of 4018 in the standard care group) or grade 2 (1447 [36·0%] of 4016 in the nirsevimab group; 1436 [35·7%] of 4018 in the standard care group) treatment-emergent adverse events, and no apparent safety concerns were raised up to 365 days after dosing. Nirsevimab offers consistent and sustained protection against hospitalisation due to RSV-associated lower respiratory tract infection for at least 6 months. This finding provides global health systems greater flexibility when implementing nirsevimab, providing substantial benefit in the ongoing effort to reduce the burden of infant RSV and the potential wider public health value. Sanofi and AstraZeneca.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in neonates, infants, and children worldwide. The virus is estimated to infect 97% of this population in the United States by the age of 2 years, leading to hospitalization for severe lower respiratory tract disease in 2-3% of infants younger than age 6 months. Two preventive options, prenatal administration of a maternal vaccine and administration of a long-acting monoclonal antibody to the infant, are now available for the prevention of RSV-associated lower respiratory tract infection in infants in the United States. The U.S. Food and Drug Administration (FDA) has approved and the Centers for Disease Control and Prevention (CDC) has recommended a new maternal vaccination, RSVPreF, to be administered between 32 0/7 and 36 6/7 weeks of gestation to reduce the risk of RSV-associated lower respiratory tract infection in infants in the first 6 months of life. The monoclonal antibody nirsevimab was approved by the FDA and recommended by the CDC for prevention of RSV-associated lower respiratory tract infection in infants younger than age 8 months who are born during or entering their first RSV season and for infants and children aged 8-19 months who are at high risk for RSV-associated lower respiratory tract infection and entering their second RSV season. Either maternal vaccination during pregnancy or monoclonal antibody administration to the infant is recommended to prevent RSV-associated lower respiratory tract infection among infants, but both are not needed for most infants. Given that the availability of these products may vary as these recommendations are implemented, it is important that obstetricians and other prenatal practitioners have the information they need to counsel their pregnant patients about both options. We review the safety and efficacy of these products, current recommendations for their use, and relative advantages and disadvantages of both newly approved options for the prevention of RSV-associated lower respiratory tract infection in infants to assist obstetricians and other prenatal practitioners in their counseling of pregnant patients.

Healthcare Utilization in Children Following Hospitalization for RSV‐ Versus Non‐RSV Related Lower Respiratory Tract Infections: A Nationwide Retrospective Study

BackgroundRespiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants.MethodsHealthy pregnant women, at 28 weeks 0 days through 36 weeks 0 days of gestation, with an expected delivery date near the start of the RSV season, were randomly assigned in an overall ratio of approximately 2:1 to receive a single intramuscular dose of RSV fusion (F) protein nanoparticle vaccine or placebo. Infants were followed for 180 days to assess outcomes related to lower respiratory tract infection and for 364 days to assess safety. The primary end point was RSV-associated, medically significant lower respiratory tract infection up to 90 days of life, and the primary analysis of vaccine efficacy against the primary end point was performed in the per-protocol population of infants (prespecified criterion for success, lower bound of the 97.52% confidence interval [CI] of ≥30%).ResultsA total of 4636 women underwent randomization, and there were 4579 live births. During the first 90 days of life, the percentage of infants with RSV-associated, medically significant lower respiratory tract infection was 1.5% in the vaccine group and 2.4% in the placebo group (vaccine efficacy, 39.4%; 97.52% CI, −1.0 to 63.7; 95% CI, 5.3 to 61.2). The corresponding percentages for RSV-associated lower respiratory tract infection with severe hypoxemia were 0.5% and 1.0% (vaccine efficacy, 48.3%; 95% CI, −8.2 to 75.3), and the percentages for hospitalization for RSV-associated lower respiratory tract infection were 2.1% and 3.7% (vaccine efficacy, 44.4%; 95% CI, 19.6 to 61.5). Local injection-site reactions among the women were more common with vaccine than with placebo (40.7% vs. 9.9%), but the percentages of participants who had other adverse events were similar in the two groups.ConclusionsRSV F protein nanoparticle vaccination in pregnant women did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. The suggestion of a possible benefit with respect to other end-point events involving RSV-associated respiratory disease in infants warrants further study. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov NCT02624947.)

Infections, Immunity &amp; their Effects on Asthma

Aims and objectives: The pandemic of COVID-19 is evolving worldwide, and it is associated with high mortality and morbidity. There is a growing need to discuss the elements of a coordinated strategy to control the spread and mitigate the severity of COVID-19. H1N1 and Streptococcus pneumonia vaccines are available. The current analysis was performed to analyze the severity of COVID-19 and influenza (H1N1) vaccination in adults ≥ 65. Also, to correlate the lower respiratory tract infections (LRIs), and influenza attributable to the lower respiratory tract infections' incidence with Covid-19 mortality. Evolutionarily influenza is close in resemblance to SARS-CoV-2 viruses and shares some common epitopes and mechanisms.Methods: Recent influenza vaccination data of 34 countries from OECD and other publications were correlated with COVID-19 mortality from worldometer data. LRIs attributable to influenza and streptococcus pneumonia were correlated with COVID-19 mortality. Specifically, influenza-attributable LRI incidence data of various countries (n = 182) was correlated with COVID-19 death by linear regression and receiver operating characteristic (ROC) curve analyzes. In a logistic regression model, population density and influenza LRI incidence were correlated with COVID-19 mortality.Results: There is a correlation between COVID-19-related mortality, morbidity, and case incidence and the status of influenza vaccination, which appears protective. The tendency of correlation is increasingly highlighted as the pandemic is evolving. In countries where influenza immunization is less common, there is a correlation between LRIs and influenza attributable to LRI incidence and COVID-19 severity, which is beneficial. ROC curve showed an area under the curve of 0.86 (CI 0.78 to 0.944, P < 0.0001) to predict COVID-19 mortality >150/million and a decreasing trend of influenza LRI episodes. To predict COVID-19 mortality of >200/million population, the odds ratio for influenza incidence/100,000 was −1.86 (CI −2.75 to −0.96, P < 0.0001). To predict the parameter Covid-19 mortality/influenza LRI episodes*1000>1000, the influenza parameter had an odd's ratio of −3.83 (CI −5.98 to −1.67), and an AUC of 0.94.Conclusion: Influenza (H1N1) vaccination can be used as an interim measure to mitigate the severity of COVID-19 in the general population. In appropriate high-risk circumstances, Streptococcus pneumonia vaccination would also be an adjunct strategy, especially in countries with a lower incidence of LRIs.

During the COVID-19 pandemic, nonpharmaceutical interventions (NPIs) were implemented in order to control the transmission of SARS-CoV-2, potentially affecting the prevalence of respiratory syncytial virus (RSV). This review evaluated the impact of NPIs on RSV-related hospitalizations in children during the lockdown (2020-2021) compared to the pre-pandemic (2015-2020) and post-lockdown (2021-2022) periods. In this systematic review and meta-analysis, we searched through PubMed, Scopus, and Web of Science for studies published in English between 1 January 2015 and 31 December 2022. Additionally, we conducted hand searches of other records published between 1 January 2023 and 22 January 2024. Our target population was hospitalized children aged 0-18 years with RSV-related lower respiratory tract infections confirmed through immunofluorescence, antigen testing, or molecular assays. We focused on peer-reviewed observational studies, analyzing the primary outcome of pooled RSV prevalence. A generalized linear mixed model with a random-effects model was utilized to pool each RSV prevalence. Heterogeneity was assessed using Cochran's Q and I2 statistics, while publication bias was evaluated through funnel plots and Egger's tests. We identified and analyzed 5815 publications and included 112 studies with 308,985 participants. Notably, RSV prevalence was significantly lower during the lockdown period (5.03% [95% CI: 2.67; 9.28]) than during the pre-pandemic period (25.60% [95% CI: 22.57; 28.88], p < 0.0001). However, RSV prevalence increased notably in the post-lockdown period after the relaxation of COVID-19 prevention measures (42.02% [95% CI: 31.49; 53.33] vs. 5.03% [95% CI: 2.67; 9.28], p < 0.0001). Most pooled effect estimates exhibited significant heterogeneity (I2: 91.2% to 99.3%). Our findings emphasize the effectiveness of NPIs in reducing RSV transmission. NPIs should be considered significant public health measures to address RSV outbreaks.

Background RSV-associated lower respiratory tract infection (LRTI) is the leading cause of infant hospitalization. Most studies of RSV have focused on infants with underlying comorbidities, including prematurity. The purpose of this analysis is to describe the burden of RSV LRTI across all medical settings and in all infants experiencing their first RSV season. Methods Using de-identified claims data from two commercial (MarketScan Commercial, MSC; Optum Clinformatics, OC) and one public (MarketScan Medicaid, MSM) insurance database, we estimated the prevalence of MA RSV LRTI among infants born between April 1, 2016 and June 30, 2019 in their first RSV season. Estimates were made by gestational age, presence/absence of comorbidities, and setting (inpatient, emergency department and outpatient). Due to limited laboratory testing, we defined MA RSV LRTI using two sets of ICD-10-CM diagnosis codes: a specific definition (identifying RSV explicitly) and a sensitive definition that included unspecified bronchiolitis. The first specific diagnosis triggered a search for another MA RSV LRTI diagnosis (either specific or sensitive) within the next 7 days. In the sensitive analysis, the first diagnosis was allowed to meet the sensitive definition. Setting was recorded as the highest level of care attached to a MA RSV LRTI diagnosis within this 7-day period. Results Using the specific (sensitive) definitions, 4.2% (12.2%), 6.8% (16.8%), and 2.7% (7.2%) of newborns had an MA RSV LRTI diagnosis during their first respiratory season across the MSC, MSM, and OC datasets (Table 1). Term infants without comorbidities accounted for 77% (83%), 79% (86%), and 80 (81%) of all MA RSV LRTI, and 21% (10%), 19% (10%), and 21% (10%) of all infants with MA RSV LRTI had an inpatient hospital stay (Table 2). Term infants without comorbidities accounted for 69% (68%), 67% (79%), and 73% (73%) of all MA RSV LRTI inpatients (Table 2). Conclusion In commercial and public claims data, during their first RSV season, term infants without comorbidities accounted for a sizable majority of inpatient, emergency room, and outpatient encounters for RSV LRTI in the US. To address the burden of RSV LRTI, future RSV prevention efforts should target all infants. Funding Sanofi Pasteur, AstraZeneca Disclosures Jason Gantenberg, MPH, Sanofi Pasteur (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Nicole Zimmerman, MS, IBM Watson Health (Employee, Nicole Zimmerman is an employee of IBM, which was compensated by Sanofi to complete this work.)Sanofi (Other Financial or Material Support, Nicole Zimmerman is an employee of IBM, which was compensated by Sanofi to complete this work.) Andrew R. Zullo, PharmD, PhD, ScM, Sanofi Pasteur (Grant/Research Support, Research Grant or Support) Brendan Limone, PharmD, PharmD, Sanofi Pasteur (Other Financial or Material Support, IBM was contracted by Sanofi to perform analysis) Clarisse Demont, n/a, Sanofi Pasteur (Employee, Shareholder) Sandra S. Chaves, MD, MSc, Sanofi Pasteur (Employee) William V. La Via, MD, AstraZeneca (Shareholder)Sanofi Pasteur (Employee) Christopher Nelson, PhD, Epidemiology, Sanofi Pasteur (Employee) Christopher Rizzo, MD, Sanofi (Employee) David A. Savitz, PhD, Sanofi Pasteur (Grant/Research Support) Robertus Van Aalst, MSc, Sanofi Pasteur (Employee, Shareholder)

Impact of respiratory syncytial virus infection as a cause of lower respiratory tract infection in children younger than 3 years of age in Japan.

Respiratory Syncytial Virus (RSV) is one of the primary pathogen responsible for severe lower respiratory tract infections in preterm infants, placing a significant burden on patients, their families, and society. Nirsevimab, a recently developed RSV monoclonal antibody, has demonstrated promising efficacy in this population according to preliminary studies. However, there remains a need for comprehensive systematic reviews and meta-analyses to evaluate the effectiveness of nirsevimab in preventing RSV-related lower respiratory tract infections in preterm infants. A search of the PubMed and EMBASE databases was conducted to identify randomized controlled trials (RCTs) and observational studies assessing the prevention of RSV infection in preterm infants using nirsevimab. Relevant data were extracted and subjected to meta-analysis. Five studies involving a total of 7,347 preterm infants (3,987 in the nirsevimab group and 3,360 in the control group) were included. The meta-analysis revealed that nirsevimab significantly reduced the incidence of medically attended RSV-associated lower respiratory tract infections (OR = 0.25; 95% CI: 0.15, 0.40; P < 0.0001) and hospitalizations due to RSV-associated lower respiratory tract infections (OR = 0.27; 95% CI: 0.19, 0.38; P < 0.0001). Nirsevimab significantly decreases the risk of RSV-related infection in preterm infants and represents a valuable intervention for RSV prevention in this vulnerable population. https://www.crd.york.ac.uk/prospero/, identifier CRD42025629937.

Rational: Human metapneumovirus (HMPV) and Respiratory syncytial virus (RSV) both can cause respiratory illness in people of all ages. The clinical syndromes associated with these two viruses are similar and range from mild upper respiratory infection to severe lower respiratory tract infections (LRTI) that require hospitalization. Here, we sought to identify peripheral blood gene expression patterns associated with HMPV- or RSV-associated LRTI in hospitalized adults. Methods: 1112 adults hospitalized with LRTI were enrolled with consent under IRB approval. All subjects underwent comprehensive microbiologic testing. Globin reduced RNA isolated from whole blood was used to generate libraries for RNASeq using the Illumina NovaSeq. We compared expression patterns for subjects with HMPV infection (n=43), RSV infection (n=54) and non-infected controls (n=62) using the Wald test in DESeq2.Results: A total of 7,352 genes passed quality control filtering criteria and were used for differential expression analysis. We identified a set of genes (n=93) showing significant differences in expression (FDR&amp;lt;0.05) in patients with HMPV versus RSV. Excluding subjects with bacterial co-infection increased the number of genes identified (n=197). Genes identified which were increased in HMPV (n=120 at log2 FC&amp;gt;0.5 of 141 at FDR&amp;lt;0.05) were associated with antigen binding, immunoglobulin production and adaptive immunity. The genes identified which were decreased in HMPV (n=16 of 56) were associated with CD8 T and NK T cells. Interestingly, fewer genes were significantly different when comparing non-infected controls to HMPV (n=0 or 2) or RSV (n=13 or 99).Summary: We can detect peripheral blood gene expression patterns for adult LRTI subjects with HMPV, which are distinct from those with RSV. The results from the study provide novel insight, which may help to guide future prophylactic and interventional strategies, and/or measure the efficacy of existing strategies.