Respiratory Syncytial Virus Transmission Research Articles

Effect of nirsevimab on hospitalisations for respiratory syncytial virus bronchiolitis in France, 2023–24: a modelling study

Respiratory syncytial virus (RSV) is a major cause of hospitalisations and deaths among infants worldwide. France was one of the first countries to implement a national programme (beginning on Sept 15, 2023) for administration of nirsevimab, a single-dose long-acting monoclonal antibody treatment, to infants born on or after Feb 6, 2023, to prevent lower respiratory tract infection caused by RSV. We aimed to estimate the effectiveness of nirsevimab and the number of hospitalisations averted in children younger than 24 months in real-world settings. In this modelling study, we developed an age-structured deterministic model characterising RSV transmission as well as plausible scenarios for the administration of nirsevimab doses based on maternity ward and community pharmacy supply data. We retrospectively estimated nirsevimab effectiveness in infants younger than 24 months during the 2023-24 RSV season in France (excluding overseas territories) and the number of averted hospitalisations for RSV bronchiolitis occurring after emergency department visits, by calibrating the model to hospital and virological surveillance data from Aug 21, 2017, to Feb 4, 2024, alongside serological data from a previous cross-sectional study. To assess the robustness of our estimates, we conducted sensitivity analyses in which we modified our assumptions about the number of doses administered, the reconstruction of the number of RSV-associated hospitalisations for bronchiolitis, the duration of maternal and post-infection immunity to RSV, and the number of contacts in children aged 0-2 months. We estimated that nirsevimab administration prevented 5800 (95% credible interval 3700-7800) RSV-associated hospitalisations for bronchiolitis after emergency department visits among children younger than 24 months, including 4200 (2900-5600) hospitalisations among those aged 0-2 months, between Sept 15, 2023 (the date nirsevimab was introduced), and Feb 4, 2024-a 23% (16-30) reduction in the total number of hospitalisations and a 35% (25-44) reduction in the 0-2 months age group, compared with the scenario without administration. In our baseline scenario, in which we estimated that 215 000 doses of nirsevimab were administered by Jan 31, 2024, the estimated effectiveness against RSV-associated hospitalisations for bronchiolitis was 73% (61-84), corresponding to one hospitalisation averted for every 39 (26-54) doses administered. In sensitivity analyses, nirsevimab remained effective against RSV-associated hospitalisations for bronchiolitis after emergency department attendance. Our findings show that nirsevimab administration campaigns could effectively reduce the RSV-related hospital burden of bronchiolitis in children younger than 24 months. European Commission, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases programme, and INCEPTION project.

Unraveling the Role of Viral Interference in Disrupting Biennial RSV Epidemics in Northern Stockholm.

Respiratory syncytial virus (RSV) primarily impacts infants and older adults, with seasonal winter outbreaks in temperate countries. Biennial cycles of RSV activity have also been identified in Northern Europe and some states in the United States. Delayed RSV activity was reported worldwide during the 2009 influenza pandemic, and a disrupted biennial pattern of RSV activity was observed in northern Stockholm following the pandemic. Biennial patterns shifted to early/large outbreaks in even-numbered years and late/small outbreaks in odd-numbered years. However, the mechanisms underpinning this change in pattern remain unknown. In this work, we constructed an age-stratified mechanistic model to explicitly test three factors that could lead to the change in RSV transmission dynamics: 1) birth rates, 2) temperatures, and 3) viral interference. By fitting the model to weekly RSV admission data over a 20-year period and comparing different models, we found that viral interference from influenza was the only mechanism that explained the shifted biennial pattern. Our work demonstrates the complex interplay between different respiratory viruses, providing evidence that supports the presence of interactions between the H1N1 pandemic influenza virus and RSV at the population level, with implications for future public health interventions.

Spatial and temporal transmission dynamics of respiratory syncytial virus in New Zealand before and after the COVID-19 pandemic.

Human respiratory syncytial virus (RSV) is a major cause of acute respiratory infection. In 2020, RSV was effectively eliminated from the community in New Zealand due to non-pharmaceutical interventions (NPI) used to control the spread of COVID-19. However, in April 2021, following a brief quarantine-free travel agreement with Australia, there was a large-scale nationwide outbreak of RSV that led to reported cases more than five times higher, and hospitalisations more than three times higher, than the typical seasonal pattern. In this study, we generated 1,471 viral genomes of both RSV-A and RSV-B sampled between 2015 and 2022 from across New Zealand. Using a phylodynamics approach, we used these data to better understand RSV transmission patterns in New Zealand prior to 2020, and how RSV became re-established in the community following the relaxation of COVID-19 restrictions. We found that in 2021, there was a large epidemic of RSV in New Zealand that affected a broader age group range compared to the usual pattern of RSV infections. This epidemic was due to an increase in RSV importations, leading to several large genomic clusters of both RSV-A ON1 and RSV-B BA9 genotypes in New Zealand. However, while a number of importations were detected, there was also a major reduction in RSV genetic diversity compared to pre-pandemic seasonal outbreaks. These genomic clusters were temporally associated with the increase of migration in 2021 due to quarantine-free travel from Australia at the time. The closest genetic relatives to the New Zealand RSV genomes, when sampled, were viral genomes sampled in Australia during a large, off-season summer outbreak several months prior, rather than cryptic lineages that were sustained but not detected in New Zealand. These data reveal the impact of NPI used during the COVID-19 pandemic on other respiratory infections and highlight the important insights that can be gained from viral genomes.

Comparison of the Burden and Temporal Pattern of Hospitalisations Associated With Respiratory Syncytial Virus (RSV) Before and After COVID-19 in New Zealand.

Changes in the epidemiology of illnesses caused by respiratory syncytial virus (RSV) infection following the COVID-19 pandemic are reported. The New Zealand (NZ) COVID-19 situation was unique; RSV community transmission was eliminated with the 2020 border closure, with a rapid and large increase in hospitalizations following the relaxation of social isolation measures and the opening of an exclusive border with Australia. This active population-based surveillance compared the age-specific incidence and seasonality of RSV-associated hospitalizations in Auckland, NZ, for 2 years before and after the 2020 border closures. Hospitalisation rates between years were compared by age, ethnicity (European/other, Māori, Pacific and Asian) and socioeconomic group (1 = least, 5 = most deprived). There was no RSV transmission in 2020. In all other years, hospitalisation rates were highest for people of Pacific versus other ethnic groups and for people living in the most deprived quintile of households. RSV hospitalisation rates were higher in 2021 and 2022 than in 2018-19. The epidemic peak was higher in 2021, but not 2022, and the duration was shorter than in 2018-19. In 2021, the increase in RSV hospitalisation rates was significant across all age, sex, ethnic and socioeconomic groups. In 2022, the increase in hospitalisation rates was only significant in one age (1- < 3 years), one ethnic (Asian) and one socioeconomic group (quintile 2). COVID pandemic responses altered RSV-related hospitalisation seasonal patterns. Atypical features of RSV hospitalisation epidemiology were the increase in rates in older children and young adults, which lessened in 2022. Despite these variations, RSV hospitalisations in NZ continue to disproportionately affect individuals of Pacific ethnicity and those living in more socioeconomically deprived households. Whilst future public health strategies focused on RSV disease mitigation need to consider the potential shifts in epidemiological patterns when the transmission is disrupted, these variances must be considered in the context of longer-standing patterns of unequal disease distribution.

School holidays and respiratory syncytial virus transmission in Sweden: An interrupted time series analysis.

Respiratory syncytial virus (RSV) represents a significant cause of morbidity for children worldwide, especially for newborns. As RSV vaccines are not routinely used for children yet, non-pharmaceutical interventions (NPIs) represent the main strategy for prevention. The objective of this study was to investigate the correlation between school holidays and RSV transmission. Data were collected from the weekly reports on RSV incidence for the 2021/2022 and 2022/2023 seasons in Sweden. The 7-day cumulative incidence of RSV was compared before and after the designated school holidays (Fall, Christmas, and Winter holidays). Our findings reveal an immediate (-1.7%, p < 0.001, 95% CI [-3.1%, -0.4%]) and gradual (-1.4%/week, p < 0.001, 95%CI [-1.8, -1.0]) reduction in RSV incidence following the Fall holiday in 2021, especially among children under 1 year of age, both immediately (-107.6%, p < 0.05, 95% CI [-203.7, -11.5]) and gradually afterwards (-58.5%/week, p < 0.001, 95% CI [-72.7, -44.3]). Mixed results were obtained for the Fall in 2022/2023 and for the Winter and holidays in both the studied years. While the Fall holiday in 2021/2022 was associated with a decrease in RSV incidence in Sweden, our results do not support a universal effect of school holidays on reducing RSV transmission.

Epidemiology of respiratory syncytial virus in hospitalized children before, during, and after the COVID-19 lockdown restriction measures in Greece.

The COVID-19 pandemic modified the epidemiology and the transmission of respiratory syncytial virus (RSV). We collected data on RSV positivity and incidence from children hospitalized in the largest tertiary paediatric hospital in Greece before (2018-2020, period A), during (2020-2021, period B), and after (2021-2023, period C) the COVID-19 lockdown. A total of 9,508 children were tested for RSV. RSV positivity (%) was 17.6% (552/3,134) for period A, 2.1% (13/629) for period B, and 13.4% (772/5,745) for period C (p < 0.001). The mean age (±SD) of RSV-positive children among the three periods was A: 5.9(±9.3), B: 13.6 (±25.3), and C: 16.7 (±28.6) months (p < 0.001). The peak of RSV epidemiology was shifted from January-March (period A) to October-December (period C). RSV in-hospital incidence per 1,000 hospitalizations in paediatric departments was A:16.7, B:1.0, and C:28.1 (p < 0.001), and the incidence in the intensive care unit was A: 17.3, B: 0.6, and C: 26.6 (p < 0.001). A decrease in RSV incidence was observed during the COVID-19 lockdown period, whereas a significant increase was observed after the lockdown. A change in epidemiological patterns was identified after the end of the lockdown, with an earlier seasonal peak and an age shift of increased RSV incidence in older children.

Respiratory syncytial virus seasonality, transmission zones, and implications for seasonal prevention strategy in China: a systematic analysis

Respiratory syncytial virus (RSV) represents a substantial global health challenge, with a disproportionately high disease burden in low-income and middle-income countries. RSV exhibits seasonality in most areas globally, and a comprehensive understanding of within-country variations in RSV seasonality could help to define the timing of RSV immunisation programmes. This study focused on China, and aimed to describe the geographical distribution of RSV seasonality, identify distinct RSV transmission zones, and evaluate the potential suitability of a seasonal RSV prevention strategy. We did a systematic analysis of RSV seasonality in China, with use of data on RSV activity extracted from a systematic review of studies published on Embase, MEDLINE, Web of Science, China National Knowledge Infrastructure, Wanfang Data, Chongqing VIP Information, and SinoMed, from database inception until May 5, 2023. We included studies of any design in China reporting at least 25 RSV cases, which aggregated RSV case number by calendar month or week at the province level, and with data covering at least 12 consecutive months before the year 2020 (prior to the COVID-19 pandemic). Studies that used only serology for RSV testing were excluded. We also included weekly data on RSV activity from open-access online databases of the Taiwan National Infection Disease Statistics System and Hong Kong Centre for Health Protection, applying the same eligiblity requirements. Across all datasets, we excluded data on RSV activity from Jan 1, 2020, onwards. We estimated RSV seasonal epidemic onset and duration using the annual average percentage (AAP) approach, and summarised seasonality at the provincial level. We used Pearson's partial correlation analysis to assess the correlation between RSV season duration and the latitude and longitude of the individual provinces. To define transmission zones, we used two independent approaches, an infant-passive-immunisation-driven approach (the moving interval approach, 6-month interval) and a data-driven approach (k-means), to identify groups of provinces with similar RSV seasonality. The systematic review was registered on PROSPERO, CRD42022376993. A total of 157 studies were included along with the two online datasets, reporting data on 194 596 RSV cases over 442 study-years (covering the period from Jan 1, 1993 to Dec 31, 2019), from 52 sites in 23 provinces. Among 21 provinces with sufficient data (≥100 reported cases), the median duration of RSV seasonal epidemics was 4·6 months (IQR 4·1-5·4), with a significant latitudinal gradient (r=-0·69, p<0·0007), in that provinces on or near the Tropic of Cancer had the longest epidemic duration. We found no correlation between longitude and epidemic duration (r=-0·15, p=0·53). 15 (71%) of 21 provinces had RSV epidemics from November to March. 13 (62%) of 21 provinces had clear RSV seasonality (epidemic duration ≤5 months). The moving interval approach categorised the 21 provinces into four RSV transmission zones. The first zone, consisting of five provinces (Fujian, Guangdong, Hong Kong, Taiwan, and Yunnan), was assessed as unsuitable for seasonal RSV immunisation strategies; the other three zones were considered suitable for seasonal RSV immunisation strategies with the optimal start month varying between September (Hebei), October (Anhui, Chongqing, Henan, Hubei, Jiangsu, Shaanxi, Shandong, Shanghai, Sichuan, and Xinjiang), and November (Beijing, Gansu, Guizhou, Hunan, and Zhejiang). The k-means approach identified two RSV transmission zones, primarily differentiated by whether the province was on or near the Tropic of Cancer (Fujian, Guangdong, Hong Kong, Taiwan, Yunan, and Hunan) or not (the remaining 15 provinces). Although substantial variations in RSV seasonality were observed across provinces of China, our study identified distinct transmission zones with shared RSV circulating patterns. These findings could have important implications for decision making on RSV passive immunisation strategy. Furthermore, the methodological framework in this study for defining RSV seasons and identifying RSV transmission zones is potentially applicable to other countries or regions. Nanjing Medical University. For the Chinese translation of the abstract see Supplementary Materials section.

Impact of Nonpharmaceutical Interventions during the COVID-19 Pandemic on the Prevalence of Respiratory Syncytial Virus in Hospitalized Children with Lower Respiratory Tract Infections: A Systematic Review and Meta-Analysis.

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.

A comparative analysis of non-pharmaceutical interventions for preventing the respiratory syncytial virus in 30 European countries.

Respiratory syncytial virus (RSV) is a leading cause of childhood respiratory infections. Non-pharmaceutical interventions (NPIs) can help to reduce RSV transmission and our aim was to provide an overview of recommended NPIs across Europe during the 2022-2023 epidemic season. The webpages of national European public health agencies and ministries were reviewed and the information they provided on RSV prevention was compared with the December 2022 guidelines from the European Centre for Disease Prevention and Control. We examined 30 countries, leading to 21 issued recommendations for RSV prevention through institutional channels, including six that were specific for the 2022-2023 season. The top five recommendations were: hand and respiratory hygiene (95%), avoiding crowded spaces (67%), staying at home when ill (62%), cleaning household items (57%) and limiting contact with sick people (57%). They also included: face masks (33%), ventilating indoor spaces (29%), properly disposing of contaminated material (13%) and keeping siblings home from preschool if there was a newborn infant in the family (10%). There was significant heterogeneity in the NPIs recommended by different countries during RSV epidemics. Ongoing evaluation is essential to optimise the effectiveness of NPIs and adapt to changing RSV patterns.

The Impact of the COVID-19 Pandemic on Respiratory Syncytial Virus Infection in the Neonatal Period.

Respiratory syncytial virus (RSV) is the most common viral respiratory infection in infants. This study aimed to establish the potential changes in the clinical course of RSV in the neonatal period with the onset of the coronavirus disease 2019(COVID-19) pandemic. During the observational study period, newborns diagnosed with community-acquired RSV infection and admitted to the neonatal intensive care unit (NICU) were evaluated. RSV-infected neonates before the COVID-19 pandemic were classified as Group 1, those during the strict isolation period as Group 2, and RSV-infected newborns after the removal of restrictions were classified as Group 3. A total of 208 community-acquired RSV-infected neonates were analyzed. The median age at admission to the NICU was 26 days, and the mean gestational week was 37.2 ± 2.7. The ratio of hospitalized babies with RSV infection to all hospitalized newborns rose after the pandemic significantly (1.9, 1.6, and 5.2%; p < 0.001). Following the pandemic, there was an increase in full-term, early-term, and late-preterm cases. Nevertheless, no change was observed in the number of preterm cases (p > 0.05). There was also a statistically significant increase in the need for intubation, noninvasive ventilation (NIV), supplemental oxygen, inhaled bronchodilator drugs, and length of hospital stay in Group 3 after the pandemic (p < 0.001). All these parameters related to more severe RSV infection when the precautions were removed, while there was a milder disease with restrictions during the pandemic in Group 2 (p < 0.001). However, none died due to RSV infection during the study because of timely supportive care. Following the COVID-19 pandemic, the frequency and severity of RSV infection in newborns have increased, and it can result in a serious clinical picture even in full-term babies with no comorbidities. Attention to strict contact precautions, particularly in newborns, who are a more vulnerable population after the pandemic, may play an important role in any future outbreak. · The course of neonatal RSV infection has changed after the pandemic.. · A statistically significant increase was observed in the need of intubation in newborns with RSV.. · The strict precautions during the pandemic also helped to prevent the transmission of RSV..

Assessing the impact of COVID-19 on epidemiological changes of severe pediatric respiratory syncytial virus infections in Malaysia.

Respiratory syncytial virus (RSV) is one of the leading causes of hospitalization and mortality among children with respiratory tract infections. The non-pharmaceutical preventive measures against severe acute respiratory syndrome coronavirus (COVID-19) may have reduced the transmission of RSV, altering its tropical epidemiological seasonality. Thus, this study represents the first attempt to evaluate changes in RSV epidemiology in the context of COVID-19 pandemic in Malaysia. Conducted at a tertiary hospital in Kuala Lumpur, Malaysia, this retrospective study analyzed collated data of children aged <12 years who were admitted for severe respiratory infections from 2017 to 2022. Time series models were used to predict the differences between actual and forecasted RSV cases, while logistic regression assessed the statistical association between RSV and COVID-19. Among the 4,084 children analyzed, we reported a significant inverse relationship between RSV and COVID-19 infections during the pandemic (2020-2021) (p < 0.05). In 2020, the RSV positivity rate sharply declined to 8.3 and 5.9%, respectively, in the two prominent seasons. Time series analysis showed a tremendous decrease in cases compared to the expected values, with reductions of 98.3% in the first season and 95.7% in the second season. However, following the lifting of the restriction order in 2022, RSV infections rose sharply with a positivity rate of 36.3%, higher than pre-COVID-19 pandemic levels. This study provides evidence of increasing RSV cases post-COVID-19 pandemic, due to immunity debt. Hence, the healthcare system must be prepared to address future RSV outbreaks with the appropriate implementation of prophylaxis and public health measures.

Evidence that an interaction between the respiratory syncytial virus F and G proteins at the distal ends of virus filaments mediates efficient multiple cycle infection.

Evidence for a stable interaction between the respiratory syncytial virus (RSV) F and G proteins on the surface of virus filaments was provided using antibody immunoprecipitation studies on purified RSV particles, and by the in situ analysis on the surface of RSV-infected cells using the proximity ligation assay. Imaging of the F and G protein distribution on virus filaments suggested that this protein complex was localised at the distal ends of the virus filaments, and suggested that this protein complex played a direct role in mediating efficient localised cell-to-cell virus transmission. G protein expression was required for efficient localised cell-to-cell transmission of RSV in cell monolayers which provided evidence that this protein complex mediates efficient multiple cycle infection. Collectively, these data provide evidence that F and G proteins form a complex on the surface of RSV particles, and that a role for this protein complex in promoting virus transmission is suggested.

Incidence and transmission of respiratory syncytial virus in urban and rural South Africa, 2017-2018

Data on respiratory syncytial virus (RSV) incidence and household transmission are limited. To describe RSV incidence and transmission, we conducted a prospective cohort study in rural and urban communities in South Africa over two seasons during 2017-2018. Nasopharyngeal swabs were collected twice-weekly for 10 months annually and tested for RSV using PCR. We tested 81,430 samples from 1,116 participants in 225 households (follow-up 90%). 32% (359/1116) of individuals had ≥1 RSV infection; 10% (37/359) had repeat infection during the same season, 33% (132/396) of infections were symptomatic, and 2% (9/396) sought medical care. Incidence was 47.2 infections/100 person-years and highest in children <5 years (78.3). Symptoms were commonest in individuals aged <12 and ≥65 years. Individuals 1-12 years accounted for 55% (134/242) of index cases. Household cumulative infection risk was 11%. On multivariable analysis, index cases with ≥2 symptoms and shedding duration >10 days were more likely to transmit; household contacts aged 1-4 years vs. ≥65 years were more likely to acquire infection. Within two South African communities, RSV attack rate was high, and most infections asymptomatic. Young children were more likely to introduce RSV into the home, and to be infected. Future studies should examine whether vaccines targeting children aged <12 years could reduce community transmission.

Respiratory syncytial virus disease morbidity in Australian infants aged 0 to 6 months: a systematic review with narrative synthesis

BackgroundA significant proportion of the global respiratory syncytial virus (RSV) associated morbidity is accounted for by infants aged 0 to 6 months, who are particularly vulnerable to severe disease. In 2015, 44% of global hospitalisations in infants in this age group were secondary to RSV. The objective of this systematic review is to appraise and synthesise the local evidence of RSV infection morbidity among Australian infants aged 0 to 6 months and to assess the implications for future immunisation strategies.MethodsElectronic databases (Medline, Embase, Pubmed and Global Health) were searched for full-text articles published between 2000 and 2023 in English language. Studies that examined markers of RSV disease morbidity in infants aged 0 to 6 months in Australia who had laboratory confirmed RSV infection were eligible for inclusion. The outcomes of interest were incidence, prevalence, testing rate, positivity rate, mortality, emergency department visits, community health visits, hospitalisation, intensive care unit admission, supplementary oxygen use, mechanical ventilation, risk factors for disease severity and monoclonal antibody use.ResultsThe database search identified 469 studies. After removal of duplicates and full-text review, 17 articles were eligible for inclusion. This review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Synthesis without meta-analysis guidelines.ConclusionsQualitative analysis of the included studies showed that Australian infants aged 0 to 6 months have higher rates of RSV testing, positivity and incidence; and more likely to develop severe disease that requires hospitalisation, intensive care unit admission or respiratory support, compared to children and adults of all ages. Aboriginal and Torres Strait Islander infants aged 0 to 6 months demonstrated higher rates of RSV infection and hospitalisation, compared to non-Indigenous infants. Age-related trends persisted in geographic areas with varying seasonal transmission of RSV, and during the SARS-CoV-2 pandemic. Passive immunisation strategies targeting infants in their first 6 months of life, either via vaccination of pregnant women or administration of long-acting monoclonal antibody during infancy, could effectively reduce RSV disease burden in Australia.

Prenatal Infection by Respiratory Viruses Is Associated with Immunoinflammatory Responses in the Fetus.

Rationale: Respiratory viral infections can be transmitted from pregnant women to their offspring, but frequency, mechanisms, and postnatal outcomes remain unclear. Objectives: The aims of this prospective cohort study were to compare the frequencies of transplacental transmission of respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), analyze the concentrations of inflammatory mediators in maternal and fetal blood, and assess clinical consequences. Methods: We recruited pregnant women who developed upper respiratory infections or tested positive for SARS-CoV-2. Maternal and cord blood samples were collected at delivery. Study questionnaires and electronic medical records were used to document demographic and medical information. Measurements and Main Results: From October 2020 to June 2022, droplet digital PCR was used to test blood mononuclear cells from 103 mother-baby dyads. Twice more newborns in our sample were vertically infected with RSV compared with SARS-CoV-2 (25.2% [26 of 103] vs. 11.9% [12 of 101]; P = 0.019). Multiplex ELISA measured significantly increased concentrations of several inflammatory cytokines and chemokines in maternal and cord blood from newborns, with evidence of viral exposure in utero compared with control dyads. Prenatal infection was associated with significantly lower birth weight and postnatal weight growth. Conclusions: Data suggest a higher frequency of vertical transmission for RSV than SARS-CoV-2. Intrauterine exposure is associated with fetal inflammation driven by soluble inflammatory mediators, with expression profiles dependent on the virus type and affecting the rate of viral transmission. Virus-induced inflammation may have pathological consequences already in the first days of life, as shown by its effects on birth weight and postnatal weight growth.

Modeling the impact of COVID-19 nonpharmaceutical interventions on respiratory syncytial virus transmission in South Africa.

The South African government employed various nonpharmaceutical interventions (NPIs) to reduce the spread of SARS-CoV-2. Surveillance data from South Africa indicates reduced circulation of respiratory syncytial virus (RSV) throughout the 2020-2021 seasons. Here, we use a mechanistic transmission model to project the rebound of RSV in the two subsequent seasons. We fit an age-structured epidemiological model to hospitalization data from national RSV surveillance in South Africa, allowing for time-varying reduction in RSV transmission during periods of COVID-19 circulation. We apply the model to project the rebound of RSV in the 2022 and 2023 seasons. We projected an early and intense outbreak of RSV in April 2022, with an age shift to older infants (6-23 months old) experiencing a larger portion of severe disease burden than typical. In March 2022, government alerts were issued to prepare the hospital system for this potentially intense outbreak. We then assess the 2022 predictions and project the 2023 season. Model predictions for 2023 indicate that RSV activity has not fully returned to normal, with a projected early and moderately intense wave. We estimate that NPIs reduced RSV transmission between 15% and 50% during periods of COVID-19 circulation. A wide range of NPIs impacted the dynamics of the RSV outbreaks throughout 2020-2023 in regard to timing, magnitude, and age structure, with important implications in a low- and middle-income countries (LMICs) setting where RSV interventions remain limited. More efforts should focus on adapting RSV models to LMIC data to project the impact of upcoming medical interventions for this disease.

2639. Role of Antimicrobial Stewardship Program (ASP) in Monitoring Community Transmission of Respiratory Syncytial Virus (RSV) to Determine Optimal Timing of Inpatient Palivizumab Administration at a Pediatric Hospital

Abstract Background The COVID-19 pandemic has impacted the transmission of RSV. Close monitoring of RSV transmission can impact optimal timing of PZ administration, as the benefit is diminished during periods of low community transmission. ASPs are in a unique position to leverage resources for monitoring epidemiology and recommending early initiation or suspension of inpatient PZ administration during periods of higher or lower RSV transmission, respectively. The role of ASPs in this capacity has not been well described. RSV positivity was determined by dividing the number of PCR tests with detectable RSV by the total number of tests performed during the specific month. Prior to the COVID-19 pandemic, inpatient palivizumab administration occurred during normal RSV seasons in the Northeast region (November to March). Prospective monitoring by the ASP was initiated in 2020 and the first suspension of inpatient palivizumab by the ASP occurred in February 2021. The dotted line represents the 3% threshold for initiation or suspension of inpatient palivizumab based on increasing or decreasing trends, respectively. Methods In 2020, the ASP initiated prospective monitoring of respiratory viral trends using the RSV positivity rate, which was provided by the microbiology laboratory. RSV positivity rate was calculated by dividing the number of tests with detectable RSV by the total number of tests performed. Inpatient PZ administration commenced once the weekly rate exceeded 3% for two consecutive weeks, regardless of the typical RSV season (i.e., November to March in the Northeast region). Inpatient administration was suspended once the weekly rate fell below 3%, along with suppression of the PZ order set in the electronic medical record. Targeted education and communication were provided to key stakeholders for initiation and suspension of PZ ordering. Results RSV transmission was 0% from November 2020 to January 2021. PZ administration was suspended in February 2021 and RSV positivity rate remained &amp;lt; 3% through April 2021 (figure 1). Administration was reinitiated in July 2021 (positivity rate 22%). The positivity rate started to decline in December 2021 and administration was suspended in February 2022 (positivity rate 1.6%). In July 2022, administration was reinitiated (positivity rate 11.4%). Administration was suspended in February 2023 (positivity rate 1.3%). The number of doses administered in each season are as follows: 52 (2018-2019), 42 (2019-2020), 14 (2020-2021), 56 (2021-2022), 65 (2022-2023). Conclusion By monitoring local epidemiology of RSV, ASPs can provide real-time recommendations for optimal timing of inpatient PZ administration. Suspension of PZ during periods of low transmission can be considered by ASPs as a cost-saving initiative. Additional studies are needed to calculate the clinical and financial impact of this ASP intervention. 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

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.

Prenatal exposure to RSV season influences first-year risk of RSV lower respiratory illness and RSV-specific immune responses assessed at birth.

Maternal-to-fetal transmission of respiratory syncytial virus (RSV) has been shown to occur but whether late prenatal exposure to RSV season influences offspring postnatal RSV-lower respiratory illness (LRI) risk in early life or RSV immune status at birth is unclear. In this study, the duration of third trimester RSV season exposure was determined for 1,094 newborns of the Tucson Children's Respiratory Study (TCRS) and found to show an inverse relation to risk for first RSV-LRI in the first year. Cord blood anti-RSV antibody is related to third trimester RSV season exposure but not to first year RSV-LRI risk. In a separate birth cohort (the Infant Immune Study), supernatants from cord blood mononuclear cells stimulated with the recall antigen, UV-inactivated RSV, were assayed for IFN-γ and IL-4. The frequency of detectable IFN-γ (but not IL-4) was increased for those with at least 2 mo of third trimester RSV season exposure, suggestive of a fetal immune response to RSV. IMPORTANCE Our study found that duration of third trimester exposure to RSV season related inversely to subsequent risk of postnatal RSV-LRI in the first year, thus implicating this exposure as an important factor in reducing risk of postnatal RSV-LRIs, a risk reduction that appears to be independent of maternally transferred anti-RSV antibody level. The increase in frequency of detectable IFN-γ and not IL-4 in response to UV-inactivated RSV in cord blood immune cells for infants with greater third trimester exposure to RSV season is suggestive of a Type-1 immune response to RSV occurring in utero.