Respiratory Syncytial Virus Hospitalization Research Articles

1746. RSV seasonality patterns change during 2016 to 2020 among hospitalized young children in Taiwan

Abstract Background Respiratory syncytial virus (RSV) is a common cause of hospitalizations in young children. Previous studies in Taiwan demonstrated seasonality of RSV hospitalization (RSVH) in young children was rather year-round with small peaks in spring and fall. This study aims to investigate recent seasonality patterns of RSVH in Taiwan using latest National Health Insurance (NHI) database. Methods We linked Taiwan birth cohort database to the NHI database for the years 2016-2020. Children < 5 years having hospital admission record with RSV ICD-10 coding were defined as having RSVH. To assess the correlations between RSVH with monthly average temperature/humidity, we used data from 2016-2019 (not including 2020 due to unusual RSV endemic) and by geographic region (Northern, Central, and Southern Taiwan). Results In children < 1 year, the annual RSVH incidence increased steadily from 1.32% in 2016, 1.55% in 2017, 1.60% in 2018, 1.67% in 2019, to 1.71% in 2020 (p=0.03). In contrast, for children aged 1-4 years, the annual RSVH incidence remained somewhat stable from 0.29%, 0.33%, 0.36%, 0.31% from 2016 to 2019, then substantially increased to 0.76% in 2020 (a 2.47-fold increase compared to 2019, p=0.22). Only one RSVH peak was observed per year for both age groups: in May for 2016, September for 2017-2019 and November for 2020. Temperature and RSVH showed high correlation among years 2016-2019, with correlation coefficients 0.64-0.68 and 0.64-0.66 in children aged < 1 and 1-4 years, respectively. However, RSVH only showed low to moderate correlation with humidity in both age groups. Conclusion The previously established seasonality patterns of RSVH in Taiwan were disrupted. A higher RSVH incidence for children aged 1-4 years was noted during 2020 endemic than previous years. Only one RSVH peak was observed in 2016-2020, and its correlation with temperature was high. Disclosures Ching-Hu Chung, PhD, Sanofi and AstraZeneca: Grant/Research Support Szu-Ying Tsai, n/a, Sanofi: employe Ting-Yu Yeh, n/a, Sanofi: employe

1678. Non-Invasive and invasive Pediatric Group A Streptococcus Infections (iGAS) Admissions During 2021 and 2022 at a Tertiary Health Care Center: Resurgence and Concomitant Viral Infections

Abstract Background A resurgence of invasive Group A Streptococcus (iGAS) infection in children was observed in Colorado and Minnesota by the Centers For Disease Control and Prevention (CDC) during the fall of 2022. Cases were accompanied by hospitalizations for respiratory syncytial virus (RSV) and influenza. We describe hospital admissions with iGAS and non iGAS infections at a tertiary health care center in Augusta, GA during 2021 and 2022; the only children’s Hospital with 150 licensed beds and a population of 201.196 as of 2021. Methods We used the iGAS definition by the CDC as a Group A Streptococcus (GAS) isolated by culture in specimens obtained from a sterile body site, or GAS isolated from wound culture and necrotizing fasciitis or streptococcal toxic shock syndrome. We conducted a retrospective chart review of iGAS and non iGAS cases admitted to the Children’s Hospital of Georgia during January to December 2021 and January to December 2022. We collected demographics, site of infection, concomitant viral infections diagnosed by nasopharyngeal (NP) PCR, intensive care unit (ICU) admission and mortality. Results During 2021, only 1 patient was admitted with non iGAS, a 7-year-old with a wound infection. In 2022, 15 patients were diagnosed with GAS infection, 7 of them had iGAS and 8 had noninvasive disease. We included positive peritoneal and pleural fluid, joint/bone aspirates, bronchoalveolar lavage samples, and blood cultures for iGAS. The age range for iGAS was 6-17 years and for noninvasive, 16 mo to 11 years. In 2022, 25% of noninvasive cases had concomitant influenza compared to 43% of iGAS cases. Only one patient with non iGAS tested positive for RSV. 2 patients had rhinovirus, one had adenovirus. One patient with iGAS was positive for metapneumovirus (HMPV). 57% of iGAS cases were admitted to the ICU (n=4). 50% of noninvasive cases (n=4) were admitted to the ICU. One iGAs case died. All noninvasive cases survived. Conclusion There was increase in iGAS and noninvasive GAS infections during 2022 compared to 2021 in our institution. iGAS was more common in older children. Of iGAS cases, the only coexisting viruses were influenza and HMPV. Most cases were seen during Fall of 2022. The cause of reappearance of iGAS and non iGAS is still unknown but believed to be related to end of mask mandates for COVID 19 infections. Disclosures All Authors: No reported disclosures

1711. Prospective Environmental Surveillance of Floors in a Pediatric Emergency Department During a Respiratory Syncytial Virus Surge in Ottawa, Canada

Abstract Background Annual respiratory syncytial virus (RSV) epidemics disproportionately impact infants and young children. Clinical surveillance is often restricted to laboratory-confirmed hospitalizations. Built environmental surveillance through floor sampling may provide population-level insights into RSV transmission dynamics and inform public health action to blunt community outbreaks.Figure:Quantification of viral detection from floor swabs in the pediatric emergency department by multiplex PCR Each point represents the number of viral copies, plus one, detected from a swab captured at a given location (y-axis) on a given date (x-axis). A value of one copy indicates non-detection of RSV. Methods A prospective environmental surveillance study was conducted in Ottawa, Canada from November 24, 2022 to March 24, 2023. Floors were swabbed in six areas of the emergency department (ED) of the sole pediatric acute care facility in Eastern Ontario. Samples were tested for RSV by a validated multiplex PCR assay. Floor swab positivity was compared to hospitalization data of patients with laboratory-confirmed RSV using Pearson’s correlation analysis to determine the degree of their association. Results Over an 18-week period, 432 floor swabs were collected in the ED and 250 pediatric patients were hospitalized. RSV was detected in 65% of floor swabs, with more viral copies detected in congregate areas (waiting rooms, triage) (Figure). The correlation between swab positivity and RSV hospitalizations was 0.64 (95%CI 0.23-0.86). Conclusion RSV was frequently detected on floors in the hospital-built environment and correlated somewhat with hospitalizations, likely reflecting community viral prevalence rather than severe RSV disease. Having real-time floor signals in different areas of the ED allowed for spatial resolution of the signal intensity, identifying higher RSV burden in areas where patients with infectious symptoms were more likely to congregate for prolonged periods of time. Floor sampling may be useful in developing spatially-refined approaches to infection prevention and control measures, particularly in indoor areas with increased respiratory viral transmission risks. Disclosures Evgueni Doukhanine, MSc, DNA Genotek: DNA Genotek provided sampling swabs in-kind for this study in an unrestricted fashion. Michael Fralick, MD, ProofDx: Advisor/Consultant

2613. Pediatric respiratory syncytial virus hospitalizations, 2017 to 2022, the Canadian Immunization Monitoring Program Active (IMPACT)

Abstract Background Respiratory syncytial virus (RSV) is a leading cause of pediatric hospitalizations. We aimed to describe the epidemiology and burden of RSV-associated hospitalizations among children in Canadian pediatric centers from 2017 to 2022, including changes during the COVID-19 pandemic. Methods We performed active surveillance for hospitalized children 0 to 16 years of age with laboratory confirmed RSV at 13 Canadian Immunization Monitoring Program Active (IMPACT) pediatric hospitals during 5 seasons (2017-18 to 2021-22). Proportions of RSV hospitalizations over all-cause hospitalizations over time, and intensive care unit (ICU) admissions, prolonged admissions (≥ 7-days) and mortality proportions were calculated, overall and by age groups and regions. RSV hospitalization-associated burden was compared for 2021-22 to the pre-pandemic period of 2017-18 to 2019-20. Seasonality was described using epidemic curves. Results Among 11,014 RSV-associated hospitalizations 6,035 (54.8%) were male and 5,488 (50%) were aged < 6 months. Overall, 2,594 (23.6%) were admitted to ICU, of which 60.8% were aged < 6 months old. The median hospital stay was 4 days (interquartile range: 2-6). The mean number of hospitalizations during the pre-pandemic seasons was 2,522. Only 58 cases were reported in 2020-21, followed by 3,170 in 2021-22. The proportion of RSV hospitalizations over all-cause hospitalizations rose from 3.2% pre-pandemic to 4.5% in 2021-22 (difference 1.3% [95%CI 0.8-1.8]; p=0.07 after multiplicity adjustment). One province, Quebec, had a significant increase in RSV-hospitalization proportion in 2021-22 (2.5 percentage points, 95%CI 1.7-3.2, adjusted p-value 0.045). Age, sex, ICU admission, prolonged length of stay(≥7-days) and mortality proportions did not change in 2021-22 compared to the pre-pandemic period. Interregional differences in RSV seasonality were accentuated in 2021-22. Weekly RSV-associated hospital admissions in children aged 0 to 16 years at IMPACT centers, 2017-2022, by season Monthly RSV-associated hospital admissions in children aged 0 to 16 years at IMPACT centers, 2017-2022, by province Conclusion RSV hospitalization burden in Canadian pediatric hospitals is substantial, especially in infants aged < 6 months. Following a near absence in 2020-21, RSV hospitalizations increased in the 2021-22 season, but severity of illness remained similar to the pre-pandemic period. These data will aid planning of RSV prevention strategies. Disclosures Nirma K. Vadlamudi, MPH, PhD, Broadstreet HEOR: Personal fees outside of the submitted work Scott Halperin, MD, CanSino: Grant/Research Support|CanSino: served on ad hoc advisory board|GlaxoSmithKline: Grant/Research Support|GlaxoSmithKline: served on ad hoc advisory board|Merck: Grant/Research Support|Merck: served on ad hoc advisory board|Moderna: Grant/Research Support|Moderna: served on ad hoc advisory board|Pfizer,: Grant/Research Support|Pfizer,: served on ad hoc advisory board|Sanofi-Pasteur: Grant/Research Support|Sanofi-Pasteur: served on ad hoc advisory board|Seqirus: Grant/Research Support|Seqirus: served on ad hoc advisory board|VBI Vaccines: Grant/Research Support|VBI Vaccines: served on ad hoc advisory board Joanne M. Langley, MD, CanSino: Grant/Research Support|Entos: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi-Pasteur: Grant/Research Support|Seqirus: Grant/Research Support|Symvivo: Grant/Research Support|VBI Vaccines: Grant/Research Support Shaun Morris, MD, MPH, DTM&H, FRCPC, FAAP, GlaxoSmithKline: Honoraria|JNJ China: Honoraria|Merck: served on ad hoc advisory board|Pfizer: Grant/Research Support|Pfizer: served on ad-hoc advisory board|Sanofi-Pasteur: served on ad-hoc advisory board Jeffrey Pernica, MD, MSc, FRCPC, DTMH, MedImmune: Grant/Research Support|Merck: Grant/Research Support Manish Sadarangani, BM BCh, FRCPC, DPhil, GlaxoSmithKline: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support|Symvivo: Grant/Research Support|VBI Vaccines: Grant/Research Support Jesse Papenburg, MD, AstraZeneca: Personal fees outside of the submitted work|MedImmune: Grant/Research Support|Merck: Grant/Research Support|Merck: Personal fees outside of the submitted work

Daily intranasal palivizumab to prevent respiratory syncytial virus infection in healthy preterm infants: a phase 1/2b randomized placebo-controlled trial

Mucosal administration of monoclonal antibodies (mAbs) against respiratory pathogens is a promising alternative for systemic administration because lower doses are required for protection. Clinical development of mucosal mAbs is a highly active field yet clinical proof-of-concept is lacking. In this investigator-initiated, double-blind, randomized placebo-controlled trial, we evaluated intranasal palivizumab for the prevention of RSV infection in preterm infants (Dutch Trial Register NTR7378 and NTR7403). We randomized infants 1:1 to receive intranasal palivizumab (1mg/mL) or placebo once daily during the RSV season. Any RSV infection was the primary outcome and RSV hospitalization was the key secondary outcome. The primary outcome was analyzed with a mixed effect logistic regression on the modified intention-to-treat population. We recruited 268 infants between Jan 14, 2019 and Jan 28, 2021, after which the trial was stopped for futility following the planned interim analysis. Adverse events were similar in both groups (22/134 (16.4%) palivizumab arm versus 26/134 (19.4%) placebo arm). There were 6 dropouts and 168 infants were excluded from the efficacy analyses due to absent RSV circulation during the SARS-CoV-2 pandemic. Any RSV infection was similar in infants in both groups (18/47 (38.3%) palivizumab arm versus 11/47 (23.4%) placebo arm; aOR 2.2, 95% CI 0.7-6.5). Daily intranasal palivizumab did not prevent RSV infection in late preterm infants. Our findings have important implications for the clinical development of mucosal mAbs, namely the necessity of timely interim analyses and further research to understand mucosal antibody half-life. Funded by the Department of Pediatrics, University Medical Centre Utrecht, the Netherlands.

Burden of respiratory syncytial virus diseases among under 5 children in Sub-Saharan Africa: A systematic review and meta-analysis

BackgroundRespiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infections (ALRIs) in young children. To design preventive efforts in sub-Saharan Africa, a better knowledge of the true role of RSV in pediatric ALRIs is required. Therefore we conducted a systematic review and meta-analysis of case–control studies to estimate the etiological role of RSV to ALRIs in under 5 years children in sub-Saharan Africa. MethodsThis study was done according to PRISMA guidelines. PubMed, EMBASE, SCOPUS, Web of Sciences databases, and Google Scholar were used to retrieve articles. STATA software version 17 was used for data analysis. The results of all the included studies were standardized to odds ratios (ORs) with accompanying 95 % confidence intervals (95 % CIs) and the pooled estimates of ORs, attributable fraction among the exposed (AFE), and population attributable fraction (PAF) were reported. The heterogeneity was assessed using Cochrane chi-square (I 2) statistics. ResultA total of 6200 cases and 4986 controls from 14 articles that fulfilled the inclusion criteria were included. The pooled prevalence of RSV among cases and controls was 23.52 % [95 % CI (20.68–26.47)] and 4.33 % [95 % CI (3.11–5.73)], respectively. The pooled OR is 7.04 [95 % CI (4.41–11.24)], which indicated a significant association between RSV and ALRI. Among ALRIs cases positive for RSV, the proportion of disease that was not attributable to the background rate (AFE) was 85.8 % [95 % CI (77.3–91.1)]. The fraction of ALRIs children that can be attributed to RSV (PAF) was 20.2 % [95 % CI (16–24.1)]. ConclusionThis study showed clear associations between RSV and ALRI hospitalization in young children in sub-Saharan Africa indicating the need for prophylactic measures against RSV in this age group.

Respiratory Syncytial Virus-Associated Hospitalization in Adults With Comorbidities in 2 European Countries: A Modeling Study.

Individuals with comorbidities are at increased risk of severe respiratory syncytial virus (RSV) infection. We estimated RSV-associated respiratory hospitalization among adults aged ≥45 years with comorbidities in Denmark and Scotland. By analyzing national hospital and virologic data, we estimated annual RSV-associated hospitalizations by 7 selected comorbidities and ages between 2010 and 2018. We estimated rate ratios of RSV-associated hospitalization for adults with comorbidity than the overall population. In Denmark, annual RSV-associated hospitalization rates per 1000 adults ranged from 3.1 for asthma to 19.4 for chronic kidney disease (CKD). In Scotland, rates ranged from 2.4 for chronic liver disease to 9.0 for chronic obstructive pulmonary disease (COPD). In both countries, we found a 2- to 4-fold increased risk of RSV hospitalization for adults with COPD, ischemic heart disease, stroke, and diabetes; a 1.5- to 3-fold increased risk for asthma; and a 3- to 7-fold increased risk for CKD. RSV hospitalization rates among adults aged 45 to 64 years with COPD, asthma, ischemic heart disease, or CKD were higher than the overall population. This study provides important evidence for identifying risk groups and assisting health authorities in RSV vaccination policy making.

The impact of non-pharmacologic interventions on respiratory syncytial virus hospitalization during the COVID-19 pandemic: A retrospective study from Saudi Arabia

BackgroundAcute respiratory tract infections (ARTIs) are frequently observed in infants and young children. The dynamics and transmission of ARTIs have been significantly impacted by the global COVID-19 pandemic. This study investigates the change in admission rates of Respiratory Syncytial virus (RSV) in a hospital in Saudi Arabia. MethodsThe study included hospitalized pediatric patients who underwent RSV testing in three periods: pre-pandemic (2019), during the pandemic (2020–2021), and the immediate post-pandemic (2022). RSV testing was conducted using either PCR or antigen tests. ResultsBetween January 2019 to December 2022, out of 927 tested patients, 173 (18.7%) were positive for RSV. The yearly positivity rates were as follows: 42 (35.6%) of 118, 24 (33.3%) of 72, 15 (18.5%) of 81, and 92 (14%) of 656, yearly from 2019 to 2022, respectively (P < 0.00001). Among all cases, 150 (16.2%) required hospitalization, including 94 (62.7%) males and 56 (37.3%) females. The admission rate to the intensive care unit (ICU) was 25 (16.7%), and mechanical ventilation was required for 10 (6.6%) patients. The overall case fatality rate was 0.7%. A Binary logistic regression analysis showed upper respiratory tract symptoms were more common in patients admitted in 2019 compared to 2022 (odd ratio:20.9, 95% CI: 4.2–104.1, P value < 0.0001). ConclusionThe study showed that there were differences in RSV infection before and after COVID-19. Understanding how COVID-19 mitigation measures affect RSV transmission can aid in the development of effective prevention and control strategies.

Inpatient burden of respiratory syncytial virus in children ≤2 years of age in Germany: A retrospective analysis of nationwide hospitalization data, 2019-2022.

Respiratory syncytial virus (RSV) causes respiratory tract disease in seasonal waves, primarily in infants and young children. This study aims to quantify the number of RSV-related hospitalizations in children ≤2 years of age and to determine corresponding resource use and costs in Germany. We retrospectively analyzed population-wide hospital data from the Institute for the Hospital Remuneration System (InEK) from 2019 to 2022. RSV cases were identified using the RSV-specific 10th revision of the International Classification of Diseases (ICD-10) codes J12.1, J20.5, and J21.0. The RSV-associated proportion of all hospitalizations caused by severe acute respiratory infections (SARIs), clinical manifestations, length of stay (LOS), intensive care unit (ICU) admissions, ventilation rates, and hospitalization costs were retrieved. We identified 98,220 hospitalizations (26,052, 15,407, 31,362, and 25,399 in 2019, 2020, 2021, and 2022, respectively) with a principal RSV diagnosis in children aged ≤2 years in Germany. The majority of RSV hospitalizations (73,178) occurred in infants (<1 year), with annual incidence rates ranging from 14.9 to 28.6 per 1000 population. Fifty-eight percent of all SARI hospitalizations in this age group were attributable to RSV. In children aged ≤2 years, mean LOS was 4.5 days, 6.1% of cases were admitted to ICU, and 5.3% of cases were ventilated. Mean hospitalization costs per case ranged from €3001 to €3961 over the study period. RSV causes substantial disease burden and is a leading cause of SARI-related hospital admissions of children ≤2 years of age in Germany. Our results confirm the need to explore and evaluate strategies to prevent RSV in infants and young children.

Risk factors for severe respiratory syncytial virus infection during the first year of life: development and validation of a clinical prediction model

Novel immunisation methods against respiratory syncytial virus (RSV) are emerging, but knowledge of risk factors for severe RSV disease is insufficient for optimal targeting of interventions against them. Our aims were to identify predictors for RSV hospital admission from registry-based data and to develop and validate a clinical prediction model to guide RSV immunoprophylaxis for infants younger than 1 year. In this model development and validation study, we studied all infants born in Finland between June 1, 1997, and May 31, 2020, and in Sweden between June 1, 2006, and May 31, 2020, along with the data for their parents and siblings. Infants were excluded if they died or were admitted to hospital for RSV within the first 7 days of life. The outcome was hospital admission due to RSV bronchiolitis during the first year of life. The Finnish study population was divided into a development dataset (born between June 1, 1997, and May 31, 2017) and a temporal hold-out validation dataset (born between June 1, 2017, and May 31, 2020). The development dataset was used for predictor discovery and selection in which we screened 1511 candidate predictors from the infants', parents', and siblings' data, and developed a logistic regression model with the 16 most important predictors. This model was then validated using the Finnish hold-out validation dataset and the Swedish dataset. In total, there were 1 124 561 infants in the Finnish development dataset, 130 352 infants in the Finnish hold-out validation dataset, and 1 459 472 infants in the Swedish dataset. In addition to known predictors such as severe congenital heart defects (adjusted odds ratio 2·89, 95% CI 2·28-3·65), we confirmed some less established predictors for RSV hospital admission, most notably oesophageal malformations (3·11, 1·86-5·19) and lower complexity congenital heart defects (1·43, 1·25-1·63). The prediction model's C-statistic was 0·766 (95% CI 0·742-0·789) in Finnish data and 0·737 (0·710-0·762) in Swedish validation data. The infants in the highest decile of predicted RSV hospital admission probability had 4·5 times higher observed risk compared with others. Calibration varied according to epidemic intensity. The model's performance was similar to a machine learning (XGboost) model using all 1511 candidate predictors (C-statistic in Finland 0·771, 95% CI 0·754-0·788). The prediction model showed clinical utility in decision curve analysis and in hypothetical number needed to treat calculations for immunisation, and its C-statistic was similar across different strata of parental income. The identified predictors and the prediction model can be used in guiding RSV immunoprophylaxis in infants, or as a basis for further immunoprophylaxis targeting tools. Sigrid Jusélius Foundation, European Research Council, Pediatric Research Foundation, and Academy of Finland.

Cost of Medically Attended RSV Among Medicaid Beneficiaries ≤2 Years of Age by Underlying Risk Condition.

We evaluated costs for respiratory syncytial virus (RSV) medical attention in children aged <24 months using MarketScan® Medicaid Multi-State claims database 2015-2019. Average cost was highest for RSV hospitalization with intensive care unit (ICU) admission ($23 514-24 835), followed by no ICU admission ($8039-8990), ED visits ($463-482), and outpatient visits ($145-151). Cost was higher for those with comorbidities.

Respiratory Syncytial Virus-Associated Hospital Admissions by Deprivation Levels Among Children and Adults in Scotland.

Socioeconomic deprivation may predispose individuals to respiratory tract infections. We estimated RSV-associated hospitalizations by socioeconomic deprivation in Scotland. Using national routine health care records and virological surveillance from 2010 to 2016, we used a time-series linear regression model and a direct measurement based on ICD-10 coded diagnoses to estimate RSV-associated hospitalizations by Scottish Index of Multiple Deprivation (SIMD) quintile and age in comparison to influenza-associated hospitalizations. We estimated an annual average rate per 1000 people of 0.76 (95% CI: 0.43-0.90) in the least deprived group to 1.51 (1.03-1.79) for the most deprived group using model-based approach. The rate ratio (RR) was 1.96 (1.23-3.25), 1.60 (1.0-2.66), 1.35 (0.85-2.25), and 1.12 (0.7-1.85) in the 1st to 4th quintile versus the least deprived group. The pattern of RSV-associated hospitalization rates variation with SIMD was most pronounced in children 0-2y. The ICD-10 approach provided much lower rates than the model-based approach but yielded similar RR estimates between SIMD. Influenza-associated hospitalization rate generally increased with higher deprivation levels among individuals 1y+. Higher RSV and influenza hospitalization rates are related to higher deprivation levels. Differences between deprivation levels are most pronounced in infants and young children for RSV, and are more apparent among individuals 1y+ for influenza.

Pediatric RSV-Associated Hospitalizations Before and During the COVID-19 Pandemic.

Respiratory syncytial virus (RSV) is a leading cause of pediatric hospitalizations. To describe the epidemiology and burden of RSV-associated hospitalizations among children and adolescents in Canadian tertiary pediatric hospitals from 2017 to 2022, including changes during the COVID-19 pandemic. This cross-sectional study was conducted during 5 RSV seasons (2017-2018 to 2021-2022) at 13 pediatric tertiary care centers from the Canadian Immunization Monitoring Program Active (IMPACT) program. Hospitalized children and adolescents aged 0 to 16 years with laboratory-confirmed RSV infection were included. The proportion of all-cause admissions associated with RSV and counts and proportions of RSV hospitalizations with intensive care unit (ICU) admission, prolonged stay (≥7 days), and in-hospital mortality were calculated overall and by season, age group, and region. Seasonality was described using epidemic curves. RSV hospitalizations for 2021-2022 were compared with those in the prepandemic period of 2017-2018 through 2019-2020. Bonferroni corrections were applied to P values to adjust for multiple statistical comparisons. Among 11 014 RSV-associated hospitalizations in children and adolescents (6035 hospitalizations among male patients [54.8%]; 5488 hospitalizations among patients aged <6 months [49.8%]), 2594 hospitalizations (23.6%) had admission to the ICU, of which 1576 hospitalizations (60.8%) were among children aged less than 6 months. The median (IQR) hospital stay was 4 (2-6) days. The mean (SD) number of RSV-associated hospitalizations during prepandemic seasons was 2522 (88.8) hospitalizations. There were 58 hospitalizations reported in 2020-2021, followed by 3170 hospitalizations in 2021-2022. The proportion of all-cause hospitalizations associated with RSV increased from a mean of 3.2% (95% CI, 3.1%-3.3%) before the pandemic to 4.5% (95% CI, 4.3%-4.6%) in 2021-2022 (difference, 1.3 percentage points; 95% CI, 1.1-1.5 percentage points; corrected P < .001). A significant increase in RSV-associated hospitalizations was found in 2021-2022 for 3 provinces (difference range, 2.5 percentage points; 95% CI, 1.4-3.6 percentage points for Quebec to 2.9 percentage points; 95% CI, 1.4-3.5 percentage points for Alberta; all corrected P < .001). Age, sex, ICU admission, prolonged length of stay, and case fatality rate did not change in 2021-2022 compared with the prepandemic period. Interregional differences in RSV seasonality were accentuated in 2021-2022, with peaks for 1 province in October, 4 provinces in December, and 3 provinces in April, or May. This study found that the burden of RSV-associated hospitalizations in Canadian pediatric hospitals was substantial, particularly among infants aged less than 6 months, and RSV hospitalizations increased in 2021-2022 compared with the prepandemic period, while severity of illness remained similar. These findings suggest that RSV preventive strategies for infants aged less than 6 months would be associated with decreased RSV disease burden in children.

Report of the WHO technical consultation on the evaluation of respiratory syncytial virus prevention cost effectiveness in low- and middle-income countries, April 7–8, 2022

Policymakers often rely on impact and cost-effectiveness evaluations to inform decisions about the introduction of health interventions in low- and middle-income countries (LMICs); however, cost-effectiveness results for the same health intervention can differ by the choice of parameter inputs, modelling assumptions, and geography. Anticipating the near-term availability of new respiratory syncytial virus (RSV) prevention products, WHO convened a two-day virtual consultation in April 2022 with stakeholder groups and global experts in health economics, epidemiology, and vaccine implementation. The objective was to review methods, parameterization, and results of existing cost-effectiveness analyses for RSV prevention in LMICs; identify the most influential inputs and data limitations; and recommend and prioritize future data gathering and research to improve RSV prevention impact estimates in LMICs. Epidemiological parameters identified as both influential and uncertain were those associated with RSV hospitalization and death, specifically setting-specific hospitalization rates and RSV-attributable death rates. Influential economic parameters included product price, delivery costs, willingness-to-pay for health on the part of potential donors, and the cost of RSV-associated hospitalization. Some of the influential parameters identified at this meeting should be more precisely measured by further research. Other influential economic parameters that are highly uncertain may not be resolved, and it is appropriate to use sensitivity analyses to explore these within cost-effectiveness evaluations. This report highlights the presentations and major discussions of the meeting.

Wastewater-based surveillance identifies start to the pediatric respiratory syncytial virus season in two cities in Ontario, Canada.

Detection of community respiratory syncytial virus (RSV) infections informs the timing of immunoprophylaxis programs and hospital preparedness for surging pediatric volumes. In many jurisdictions, this relies upon RSV clinical test positivity and hospitalization (RSVH) trends, which are lagging indicators. Wastewater-based surveillance (WBS) may be a novel strategy to accurately identify the start of the RSV season and guide immunoprophylaxis administration and hospital preparedness. We compared citywide wastewater samples and pediatric RSVH in Ottawa and Hamilton between August 1, 2022, and March 5, 2023. 24-h composite wastewater samples were collected daily and 5 days a week at the wastewater treatment facilities in Ottawa and Hamilton, Ontario, Canada, respectively. RSV WBS samples were analyzed in real-time for RSV by RT-qPCR. RSV WBS measurements in both Ottawa and Hamilton showed a lead time of 12 days when comparing the WBS data set to pediatric RSVH data set (Spearman's ρ = 0.90). WBS identify early RSV community transmission and declared the start of the RSV season 36 and 12 days in advance of the provincial RSV season start (October 31) for the city of Ottawa and Hamilton, respectively. The differing RSV start dates in the two cities is likely associated with geographical and regional variation in the incidence of RSV between the cities. Quantifying RSV in municipal wastewater forecasted a 12-day lead time of the pediatric RSVH surge and an earlier season start date compared to the provincial start date. These findings suggest an important role for RSV WBS to inform regional health system preparedness, reduce RSV burden, and understand variations in community-related illness as novel RSV vaccines and monoclonal antibodies become available.

The Estimate of Parental Quality of Life Loss Due to Respiratory Syncytial Virus (RSV) Hospitalization.

Respiratory syncytial virus (RSV) is one of the leading causes of pediatric hospitalizations, mainly in children under 2 years of age. Hospitalization affects the caregivers' quality of life (QoL). We assessed the caregivers' QoL during RSV-confirmed hospitalizations of children under 2 years old, identified the most affected QoL dimensions and calculated utilities focusing on the assessment methods and potential confounders. The caregivers filled out the EQ-5D questionnaire, consisting of a descriptive system (assessing 5 QoL dimensions) and a visual analog scale (EQ VAS). Utility, utility loss and quality-adjusted life years (QALY) loss were calculated, and a concordance between the two systems was assessed. A disturbance in any of the five assessed dimensions was reported by 42% (55 out of 132) of the caregivers, mostly anxiety/depression (37%) and pain/discomfort (17%). The utilities varied between 0.17 and 1 in the descriptive system and 0.33-1 (median 0.86) in the EQ VAS, with a utility loss of 0.14 (IQR: 0.1-0.2). The calculated QALY loss reached a median of 2.45 × 10-3 (IQR: 1.37 × 10-3-4.56 × 10-3) and was not influenced by the patient's age or the final clinical diagnosis (QALY loss for bronchiolitis: 2.74 × 10-3, pneumonia: 1.84 × 10-3, bronchitis: 1.78 × 10-3, differences statistically insignificant). Only a moderate concordance between the descriptive system and the EQ VAS was seen (Spearman's rank correlation coefficient = 0.437, p < 0.05), with the latter revealing a higher degree of QoL disturbances. RSV hospitalization influences parental QoL significantly, and anxiety/depression is the most commonly reported issue. Utility impairment scores depend on the assessment method but not on the patient's age or final diagnosis. Thus, the impact of RSV on caregivers' QoL cannot be underestimated.

50 New Analysis on the Cost-effectiveness of Palivizumab (PVZ) for the Prevention of Severe Respiratory Syncytial Virus (RSV) Infection in Canadian Infants Born 29-31 and 32-35 weeks’ Gestational Age (wGA)

Abstract Background PVZ remains the only licensed intervention to prevent severe RSV infection. The last formal cost-utility analysis (CUA) of its use in Canadian premature infants was published in 2010 (Smart J Med Econ 2010). Since then, the 3-variable International Risk Scoring tool (IRST) has been published (Blanken Pediatr Pulmonol 2018), which can guide prophylaxis for infants born 32-35 wGA at greatest risk of RSV hospitalization (RSVH). Objectives The objective of this study was to incorporate the IRST and non-hospitalized, medically-attended (emergency room/outpatient) RSV infections (MARI) into a CUA for the first time to provide an up-to-date economic evaluation of palivizumab versus no prophylaxis in Canadian 29-31 wGA and 32-35 wGA infants. Design/Methods Infants followed a semi-Markov process, having an RSVH, MARI, or being uninfected/non-medically attended. Hospitalized infants could be admitted to the intensive care unit (ICU; 17.9%) and ICU-admitted infants could die (0.43%). All surviving infants could experience respiratory morbidity up to 18 years, according to RSV infection and PVZ status. The RSVH rate in non-prophylaxed 29-31 wGA and moderate to high (MH) risk 32-35 wGA infants was 5.9% and 6.3%, respectively. PVZ reduced RSVH by 63.3% and 82.2% in 29-31 wGA and 32-35 wGA infants, respectively. PVZ costs (assuming 50 mg: CAN$752; 100 mg: $1,505) were calculated using Canadian birth statistics. The base case assumed all 29-31 wGA infants and MH-risk 32-35 wGA infants received PVZ, inclusion of indirect costs, no vial sharing, and a lifetime time horizon with 1.5% discounting. A cost per quality-adjusted life-year (QALY) of ≤$50,000 was considered cost-effective. Results PVZ prophylaxis resulted in a cost/QALY of $29,579 in 29-31 wGA infants and $27,951 in MH-risk 32-35 wGA infants versus no prophylaxis. In deterministic sensitivity analyses (±20% on main variables) the model was most sensitive to utility scores, PVZ cost, non-prophylaxed RSVH rate, and PVZ efficacy. Probabilistic sensitivity analyses (10,000 iterations) resulted in incremental costs of $30,857/QALY, with a 76.0% probability of cost-effectiveness at a $50,000 willingness-to-pay threshold for 29-31 wGA infants, and $28,167/QALY and 79.1% for MH-risk 32-35 wGA infants. Conclusion This new CUA, the first to incorporate the IRST and MARI, found that PVZ is highly cost-effective in Canadian 29-35 wGA infants (vs no prophylaxis) and has implications for prophylaxis policies in Canada. Potential competing interests Xavier Carbonell-Estrany and Bosco Paes have received research funding and/or compensation as advisor/lecturer from AbbVie and AstraZeneca. Jean-Eric Tarride has nothing to disclose. Barry Rodgers-Gray, Ian Keary and John Fullarton employers have received payment from AbbVie and AstraZeneca for work on various projects.

Cost-effectiveness of nirsevimab and palivizumab for respiratory syncytial virus prophylaxis in preterm infants 29–34 6/7 weeks' gestation in the United States

Respiratory syncytial virus (RSV) hospitalizations have increased since the 2014 guideline update recommended against the use of palivizumab for preterm infants born ≥29 0/7 weeks' gestational age (GA) without additional risk factors. A novel drug candidate, nirsevimab, has been developed for this population. We analyzed the cost-effectiveness of palivizumab/nirsevimab vs. no prophylaxis in this population. A hybrid-Markov model predicted the RSV clinical course in the first year of life and sequelae in the subsequent four years for preterm infants from the healthcare and societal perspectives. Model parameters were derived from the literature. We calculated costs and quality-adjusted life-years (QALYs) to produce an incremental cost-effectiveness ratio (ICER) evaluated at a willingness-to-pay threshold of $150,000/QALY. Sensitivity analyses assessed model robustness. A threshold analysis examined nirsevimab pricing uncertainty. Compared to no prophylaxis, palivizumab costs $9572 and $9584 more from the healthcare and societal perspectives, respectively, with 0.0019 QALYs gained per patient over five years, resulting in ICERs >$5 million per QALY from each perspective. Results were robust to parameter uncertainties; probabilistic sensitivity analysis revealed that no prophylaxis had a 100% probability of being cost-effective. The threshold analysis suggested that nirsevimab is not cost-effective when compared to no prophylaxis if the price exceeds $1962 from a societal perspective. Palivizumab is dominated by no prophylaxis for preterm infants 29 0/7-34 6/7 weeks' GA with no additional risk factors. Relevant stakeholders should consider alternatives to palivizumab for this population that are both effective and economical.

Potential benefits of expanded palivizumab in American Indian children under the age of 2-years.

Respiratory syncytial virus (RSV) causes a severe respiratory syndrome that disparately impacts American Indian communities. We significantly reduced RSV-related infections and hospitalizations through the expanded the use of palivizumab, an approved yet commonly restricted prophylactic monoclonal therapy.

Genome-wide Association Study of Susceptibility to Respiratory Syncytial Virus Hospitalization in Young Children

Worldwide, respiratory syncytial virus (RSV) infections are among the most common causes of infant hospitalization. Host genetic factors influencing the risk and severity of RSV infection are not well known. We conducted a genome-wide association study (GWAS) to investigate single-nucleotide polymorphisms (SNPs) associated with severe RSV infections using a nested case-control design based on 2 Danish cohorts. We compared SNPs from 1786 children hospitalized with RSV to 45 060 controls without an RSV-coded hospitalization. We performed gene-based testing, tissue enrichment, gene-set enrichment, and a meta-analysis of the 2 cohorts. Finally, an analysis of potential associations between the severity of RSV infection and genetic markers was performed. We did not detect any significant genome-wide associations between SNPs and RSV infection or the severity of RSV. We did find potential loci associated with RSV infections on chromosome 5 in 1 cohort but failed to replicate any signals in both cohorts. Despite being the largest GWAS of severe RSV infection, we did not detect any genome-wide significant loci. This may be an indication of a lack of power or an absence of signal. Future studies might include mild illness and need to be larger to detect any significant associations.