Characterising the changes in RSV epidemiology in Beijing, China during 2015-2023: results from a prospective, multi-centre, hospital-based surveillance and serology study.

Background: Respiratory syncytial virus (RSV) has posed substantial morbidity and mortality burden to young children and older adults globally. The coronavirus disease 2019 (COVID-19) pandemic was reported to have altered RSV epidemiology and could have important implications for RSV prevention and control strategies. We aimed to compare RSV epidemiology in different phases of the COVID-19 pandemic with the pre-pandemic period by leveraging epidemiological, molecular, and serological data collected from a prospective respiratory pathogen surveillance and serology study. Methods: This study was based on the data during July 1, 2015 to November 30, 2023 from the Respiratory Pathogen Surveillance System (RPSS), a sentinel-hospital based surveillance system of acute respiratory infections consisting of 35 hospitals that represent residents of all ages from all 16 districts in Beijing, China. RSV infection status was tested by RT-PCR and gene sequencing and phylogenetic analysis was conducted among the identified RSV strains. We further supplemented RPSS data with three serology surveys conducted during 2017-2023 that tested RSV IgG levels from serum specimens. RSV detection rate was calculated by calendar month and compared across RSV seasons (defined as the July 1 through June 30 of the following year). RSV IgG positivity proportion was calculated by quarter of the year and was correlated with quarterly aggregated RSV detection rate for understanding the relationship between infection and immunity at the population level. Findings: Overall, a total of 52,931 respiratory specimens were collected and tested over the study period. RSV detection rates ranged from 1.24% (94/7594) in the 2017-2018 season to 2.80% (219/7824) in the 2018-2019 season, and from 1.06% (55/5165) in the 2022-2023 season to 2.98% (147/4938) in the 2021-2022 season during the pre-pandemic and pandemic period, respectively. ON1 and BA9 remained the predominant genotypes during the pandemic period; no novel RSV strains were identified. RSV circulation followed a winter-months seasonal pattern in most seasons. One exception was the 2020-2021 season when an extensive year-round circulation was observed, possibly associated with partial relaxation of non-pharmaceutical interventions (NPIs). The other exception was the 2022-2023 season when very low RSV activity was observed during the usual winter months (possibly due to the concurrent local COVID-19 epidemic), and followed by an out-of-season resurgence in the spring, with RSV detection persisting to the end of the study period (November 2023). During the two seasons above, we noted an age-group related asynchrony in the RSV detection rate; the RSV detection rate in young children remained similar (or even increased with borderline significance; 43/594, 7.24%, and 42/556, 7.55% vs 292/5293, 5.52%; P = 0.10 and P = 0.06, respectively) compared with the pre-pandemic seasons whereas the detection rate in older adults decreased significantly (8/1779, 0.45%, and 3/2021, 0.15% vs 160/10,348, 1.55%; P < 0.001 in two comparisons). Results from serology surveys showed significantly declined RSV IgG positivity in the 2022-2023 season compared to the pre-pandemic seasons (9.32%, 29/311 vs 20.16%, 100/496; P < 0.001); older adults had significantly higher RSV IgG positivity than young children in both pre-pandemic and pandemic periods (P values < 0.001). Interpretation: Our study documented the trajectory of RSV detection along with the changes in the stringency of NPIs, measured IgG positivity, and local COVID-19 epidemics. The findings suggest the interplay between contact patterns, immunity dynamics, and SARS-CoV-2 infection in shaping the RSV epidemics of population of different ages. These findings provide novel insights into the potential drivers of RSV circulating patterns and have important implications for RSV prevention and control strategies. Funding: The High-qualified Public Health Professionals Development Project, Capital's Funds for Health Improvement and Research, and the Public Health Personnel Training Support Program.

Global disease burden of and risk factors for acute lower respiratory infections caused by respiratory syncytial virus in preterm infants and young children in 2019: a systematic review and meta-analysis of aggregated and individual participant data.

BACKGROUND: Infants and young children born prematurely are at high risk of severe acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV). In this study, we aimed to assess the global disease burden of and risk factors for RSV-associated ALRI in infants and young children born before 37 weeks of gestation. METHODS: We conducted a systematic review and meta-analysis of aggregated data from studies published between Jan 1, 1995, and Dec 31, 2021, identified from MEDLINE, Embase, and Global Health, and individual participant data shared by the Respiratory Virus Global Epidemiology Network on respiratory infectious diseases. We estimated RSV-associated ALRI incidence in community, hospital admission, in-hospital mortality, and overall mortality among children younger than 2 years born prematurely. We conducted two-stage random-effects meta-regression analyses accounting for chronological age groups, gestational age bands (early preterm, <32 weeks gestational age [wGA], and late preterm, 32 to <37 wGA), and changes over 5-year intervals from 2000 to 2019. Using individual participant data, we assessed perinatal, sociodemographic, and household factors, and underlying medical conditions for RSV-associated ALRI incidence, hospital admission, and three severity outcome groups (longer hospital stay [>4 days], use of supplemental oxygen and mechanical ventilation, or intensive care unit admission) by estimating pooled odds ratios (ORs) through a two-stage meta-analysis (multivariate logistic regression and random-effects meta-analysis). This study is registered with PROSPERO, CRD42021269742. FINDINGS: We included 47 studies from the literature and 17 studies with individual participant-level data contributed by the participating investigators. We estimated that, in 2019, 1 650 000 (95% uncertainty range [UR] 1 350 000-1 990 000) RSV-associated ALRI episodes, 533 000 (385 000-730 000) RSV-associated hospital admissions, 3050 (1080-8620) RSV-associated in-hospital deaths, and 26 760 (11 190-46 240) RSV-attributable deaths occurred in preterm infants worldwide. Among early preterm infants, the RSV-associated ALRI incidence rate and hospitalisation rate were significantly higher (rate ratio [RR] ranging from 1·69 to 3·87 across different age groups and outcomes) than for all infants born at any gestational age. In the second year of life, early preterm infants and young children had a similar incidence rate but still a significantly higher hospitalisation rate (RR 2·26 [95% UR 1·27-3·98]) compared with all infants and young children. Although late preterm infants had RSV-associated ALRI incidence rates similar to that of all infants younger than 1 year, they had higher RSV-associated ALRI hospitalisation rate in the first 6 months (RR 1·93 [1·11-3·26]). Overall, preterm infants accounted for 25% (95% UR 16-37) of RSV-associated ALRI hospitalisations in all infants of any gestational age. RSV-associated ALRI in-hospital case fatality ratio in preterm infants was similar to all infants. The factors identified to be associated with RSV-associated ALRI incidence were mainly perinatal and sociodemographic characteristics, and factors associated with severe outcomes from infection were mainly underlying medical conditions including congenital heart disease, tracheostomy, bronchopulmonary dysplasia, chronic lung disease, or Down syndrome (with ORs ranging from 1·40 to 4·23). INTERPRETATION: Preterm infants face a disproportionately high burden of RSV-associated disease, accounting for 25% of RSV hospitalisation burden. Early preterm infants have a substantial RSV hospitalisation burden persisting into the second year of life. Preventive products for RSV can have a substantial public health impact by preventing RSV-associated ALRI and severe outcomes from infection in preterm infants. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe.

Changes in the global hospitalisation burden of respiratory syncytial virus in young children during the COVID-19 pandemic: a systematic analysis.

BACKGROUND: The COVID-19 pandemic is reported to have affected the epidemiology of respiratory syncytial virus (RSV), which could have important implications for RSV prevention and control strategies. We aimed to assess the hospitalisation burden of RSV-associated acute lower respiratory infection (ALRI) in children younger than 5 years during the pandemic period and the possible changes in RSV epidemiology from a global perspective. METHODS: We conducted a systematic literature search for studies published between Jan 1, 2020, and June 30, 2022, in MEDLINE, Embase, Global Health, Web of Science, the WHO COVID-19 Research Database, CINAHL, LILACS, OpenGrey, CNKI, WanFang, and CqVip. We included unpublished data on RSV epidemiology shared by international collaborators. Eligible studies reported data on at least one of the following measures for children (aged <5 years) hospitalised with RSV-associated ALRI: hospital admission rates, in-hospital case fatality ratio, and the proportion of hospitalised children requiring supplemental oxygen or requiring mechanical ventilation or admission to intensive care. We used a generalised linear mixed-effects model for data synthesis to measure the changes in the incidence, age distribution, and disease severity of children hospitalised with RSV-associated ALRI during the pandemic, compared with the year 2019. FINDINGS: We included 61 studies from 19 countries, of which 14 (23%) studies were from the published literature (4052 identified records) and 47 (77%) were from unpublished datasets. Most (51 [84%]) studies were from high-income countries; nine (15%) were from upper-middle-income countries, one (2%) was from a lower-middle-income country (Kenya), and none were from a low-income country. 15 studies contributed to the estimates of hospitalisation rate and 57 studies contributed to the severity analyses. Compared with 2019, the rates of RSV-associated ALRI hospitalisation in all children (aged 0-60 months) in 2020 decreased by 79·7% (325 000 cases vs 66 000 cases) in high-income countries, 13·8% (581 000 cases vs 501 000 cases) in upper-middle-income countries, and 42·3% (1 378 000 cases vs 795 000 cases) in Kenya. In high-income countries, annualised rates started to rise in 2021, and by March, 2022, had returned to a level similar to 2019 (6·0 cases per 1000 children [95% uncertainty interval 5·4-6·8] in April, 2021, to March, 2022, vs 5·0 cases per 1000 children [3·6-6·8] in 2019). By contrast, in middle-income countries, rates remained lower in the latest period with data available than in 2019 (for upper-middle-income countries, 2·1 cases [0·7-6·1] in April, 2021, to March, 2022, vs 3·4 [1·2-9·7] in 2019; for Kenya, 2·2 cases [1·8-2·7] in 2021 vs 4·1 [3·5-4·7] in 2019). Across all time periods and income regions, hospitalisation rates peaked in younger infants (aged 0 to <3 months) and decreased with increasing age. A significantly higher proportion of children aged 12-24 months were hospitalised with RSV-associated ALRI in high-income and upper-middle-income countries during the pandemic years than in 2019, with odds ratios ranging from 1·30 (95% uncertainty interval 1·07-1·59) to 2·05 (1·66-2·54). No consistent changes in disease severity were observed. INTERPRETATION: The hospitalisation burden of RSV-associated ALRI in children younger than 5 years was significantly reduced during the first year of the COVID-19 pandemic. The rebound in hospitalisation rates to pre-pandemic rates observed in the high-income region but not in the middle-income region by March, 2022, suggests a persistent negative impact of the pandemic on health-care systems and health-care access in the middle-income region. RSV surveillance needs to be established (or re-established) to monitor changes in RSV epidemiology, particularly in low-income and lower-middle-income countries. FUNDING: EU Innovative Medicines Initiative Preparing for RSV Immunisation and Surveillance in Europe (PROMISE), Bill & Melinda Gates Foundation, and WHO.

Understanding the age spectrum of respiratory syncytial virus associated hospitalisation and mortality burden based on statistical modelling methods: a systematic analysis.

BACKGROUND: Statistical modelling studies based on excess morbidity and mortality are important for understanding RSV disease burden for age groups that are less frequently tested for RSV. We aimed to understand the full age spectrum of RSV morbidity and mortality burden based on statistical modelling studies, as well as the value of modelling studies in RSV disease burden estimation. METHODS: The databases Medline, Embase and Global Health were searched to identify studies published between January 1, 1995, and December 31, 2021, reporting RSV-associated excess hospitalisation or mortality rates of any case definitions using a modelling approach. All reported rates were summarised using median, IQR (Interquartile range) and range by age group, outcome and country income group; where applicable, a random-effects meta-analysis was conducted to combine the reported rates. We further estimated the proportion of RSV hospitalisations that could be captured in clinical databases. RESULTS: A total of 32 studies were included, with 26 studies from high-income countries. RSV-associated hospitalisation and mortality rates both showed a U-shape age pattern. Lowest and highest RSV acute respiratory infection (ARI) hospitalisation rates were found in 5-17 years (median: 1.6/100,000 population, IQR: 1.3-18.5) and < 1 year (2235.7/100,000 population, 1779.1-3552.5), respectively. Lowest and highest RSV mortality rates were found in 18-49 years (0.1/100,000 population, 0.06-0.2) and ≥ 75 years (80.0/100,000 population, 70.0-90.0) for high-income countries, respectively, and in 18-49 years (0.3/100,000 population, 0.1-2.4) and < 1 year (143.4/100,000 population, 143.4-143.4) for upper-middle income countries. More than 70% of RSV hospitalisations in children < 5 years could be captured in clinical databases whereas less than 10% of RSV hospitalisations could be captured in adults, especially for adults ≥ 50 years. Using pneumonia and influenza (P&I) mortality could potentially capture half of all RSV mortality in older adults but only 10-30% of RSV mortality in children. CONCLUSIONS: Our study provides insights into the age spectrum of RSV hospitalisation and mortality. RSV disease burden using laboratory records alone could be substantially severely underreported for age groups ≥ 5 years. Our findings confirm infants and older adults should be prioritised for RSV immunisation programmes. TRIAL REGISTRATION: PROSPERO CRD42020173430.

Understanding the risk of transmission of respiratory viral infections in childcare centres: protocol for the DISeases TrANsmission in ChildcarE (DISTANCE) multicentre cohort study.

INTRODUCTION: Childcare centre is considered a high-risk setting for transmission of respiratory viruses. Further evidence is needed to understand the risk of transmission in childcare centres. To this end, we established the DISeases TrANsmission in ChildcarE (DISTANCE) study to understand the interaction among contact patterns, detection of respiratory viruses from environment samples and transmission of viral infections in childcare centres. METHODS AND ANALYSIS: The DISTANCE study is a prospective cohort study in multiple childcare centres of Jiangsu Province, China. Study subjects will be childcare attendees and teaching staff of different grades. A range of information will be collected from the study subjects and participating childcare centres, including attendance, contact behaviours (collected by onsite observers), respiratory viral infection (weekly respiratory throat swabs tested by multiplex PCR), presence of respiratory viruses on touch surfaces of childcare centres and weekly follow-up survey on respiratory symptoms and healthcare seeking among subjects tested positive for any respiratory viruses. Detection patterns of respiratory viruses from study subjects and environment samples, contact patterns, and transmission risk will be analysed by developing statistical and mathematical models as appropriate. The study has been initiated in September 2022 in 1 childcare centre in Wuxi City, with a total of 104 children and 12 teaching staff included in the cohort; data collection and follow-up is ongoing. One more childcare centre in Nanjing City (anticipated to include 100 children and 10 teaching staff) will start recruitment in 2023. ETHICS AND DISSEMINATION: The study has received ethics approval from Nanjing Medical University Ethics Committee (No. 2022-936) and ethics approval from Wuxi Center for Disease Control and Prevention Ethics Committee (No. 2022-011). We plan to disseminate the study findings mainly through publications in peer-reviewed journals and presentations in academic conferences. Aggregated research data will be shared freely to researchers.

The role of respiratory co-infection with influenza or respiratory syncytial virus in the clinical severity of COVID-19 patients: A systematic review and meta-analysis.

Background: With the easing of COVID-19 non-pharmaceutical interventions, the resurgence of both influenza and respiratory syncytial virus (RSV) was observed in several countries globally after remaining low in activity for over a year. However, whether co-infection with influenza or RSV influences disease severity in COVID-19 patients has not yet been determined clearly. We aimed to understand the impact of influenza/RSV co-infection on clinical disease severity among COVID-19 patients. Methods: We conducted a systematic literature review of publications comparing the clinical severity between the co-infection group (ie, influenza/RSV with SARS-CoV-2) and mono-infection group (ie, SARS-CoV-2), using the following four outcomes: need or use of supplemental oxygen, intensive care unit (ICU) admission, mechanical ventilation, and deaths. We summarized the results by clinical outcome and conducted random-effect meta-analyses where applicable. Results: Twelve studies reporting a total of 7862 COVID-19 patients were included in the review. Influenza and SARS-CoV-2 co-infection were found to be associated with a higher risk of ICU admission (five studies, odds ratio (OR) = 2.09, 95% confidence interval (CI) = 1.64-2.68) and mechanical ventilation (five studies, OR = 2.31, 95% CI = 1.10-4.85). No significant association was found between influenza co-infection and need/use of supplemental oxygen or deaths among COVID-19 patients (four studies, OR = 1.04, 95% CI = 0.37-2.95; 11 studies, OR = 1.41, 95% CI = 0.65-3.08, respectively). For RSV co-infection, data were only sufficient to allow for analyses for the outcome of deaths, and no significant association was found between RSV co-infection and deaths among COVID-19 patients (three studies, OR = 5.27, 95% CI = 0.58-47.87). Conclusions: Existing evidence suggests that co-infection with influenza might be associated with a 2-fold increase in the risk for ICU admission and for mechanical ventilation among COVID-19 patients whereas evidence is limited on the role of RSV co-infection. Co-infection with influenza does not increase the risk of death in COVID-19 patients. Registration: PROSEPRO CRD42021283045.

Understanding the Potential Drivers for Respiratory Syncytial Virus Rebound During the Coronavirus Disease 2019 Pandemic.

Nonpharmaceutical interventions (NPIs) were widely introduced to combat the coronavirus disease 2019 (COVID-19) pandemic. These interventions also likely led to substantially reduced activity of respiratory syncytial virus (RSV). From late 2020, some countries observed out-of-season RSV epidemics. Here, we analyzed the role of NPIs, population mobility, climate, and severe acute respiratory syndrome coronavirus 2 circulation in RSV rebound through a time-to-event analysis across 18 countries. Full (re)opening of schools was associated with an increased risk for RSV rebound (hazard ratio [HR], 23.29 [95% confidence interval {CI}, 1.09-495.84]); every 5°C increase in temperature was associated with a decreased risk (HR, 0.63 [95% CI, .40-.99]). There was an increasing trend in the risk for RSV rebound over time, highlighting the role of increased population susceptibility. No other factors were found to be statistically significant. Further analysis suggests that increasing population susceptibility and full (re)opening of schools could both override the countereffect of high temperatures, which explains the out-of-season RSV epidemics during the COVID-19 pandemic.