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

Background The coronavirus disease 2019 (COVID-19) pandemic was reported to have impacted RSV epidemiology and could have important implications for RSV prevention and control strategies. We aimed to understand the RSV-associated acute lower respiratory infection (ALRI) hospitalisation burden in children younger than five years during the COVID-19 pandemic period and the possible changes in RSV epidemiology from a global perspective.Methods We conducted a systematic literature search for studies published between January 1, 2020 and June 30, 2022, from MEDLINE (Ovid), Embase (Ovid), Global Health (Ovid), Web of Science, WHO COVID-19 database, CINAHL, LILACS, OpenGrey, CNKI, WanFang and ChongqingVIP. We included unpublished RSV epidemiology data shared by international collaborators. Eligible studies reported data for RSV-associated ALRI hospital admission rates or at least one of the following severity measures: the proportion of RSV cases that needed supplemental oxygen, mechanical ventilation or intensive care unit admission, and in-hospital case fatality ratio. A generalised linear mixed-effects model was used for data synthesis to understand the changes in the incidence, age distribution and severity of RSV-associated ALRI hospitalisations in children under five years during the COVID-19 pandemic, compared to the year 2019. Findings We included 61 studies, 14 studies from published literature and 47 unpublished datasets. Most studies (51/61) were from the high-income region, followed by the upper-middle-income region (9/61); only one study was from the lower-middle-income region, and no studies were from the low-income region. Compared to 2019, all income regions saw substantial decreases in RSV-associated ALRI hospitalisation rate across all age groups in 2020; the number of RSV-associated ALRI hospitalisations in children aged 0–&lt;60 months decreased by approximately 80% (325,000 to 66,000), 14% (581,000 to 501,000) and 42% (1,378,000 to 795,000) for high-income, upper-middle-income and lower-middle-income countries, respectively. RSV hospitalisation rate started to rise in 2021, and by March 2022, the annualised rate returned to a level comparable to 2019 (6·0/1000, 95% uncertainty interval [UI] 5·4–6·8 by March 2022 vs 5·0/1000, 3·6–6·8 in 2019) in high-income countries while remaining lower in middle-income countries. Across all time periods and income regions, RSV-associated ALRI hospitalisation rates peaked in infants aged 0–&lt;3 months and declined with increasing age. Compared to the pre-pandemic period, there was a significantly increased proportion of RSV-associated ALRI hospitalisations in those aged 12–&lt;24 months in high-income and upper-middle-income regions (ORs ranged from 1·30 [1·07–1·59] to 2·05 [1·66–2·54]). No consistent changes in disease severity were observed. Interpretation Our study documented a significant reduction in RSV-associated ALRI hospitalisation burden in children under five years during the first year of the COVID-19 pandemic. A rebound to pre-pandemic levels in RSV-associated ALRI hospitalisation rate was observed in the high-income region by March 2022 but not in the middle-income region, suggesting a more persistent negative impact of the COVID-19 pandemic on health-care systems and health-care access in middle-income regions. RSV surveillance needs to be established (or re-established) to monitor the changes in RSV epidemiology, particularly in low- and lower-middle-income countries.Funding EU Innovative Medicines Initiative Preparing for RSV Immunisation and Surveillance in Europe (PROMISE); Bill &amp; Melinda Gates Foundation; World Health Organization. <br/

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study.

BACKGROUND: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. METHODS: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. FINDINGS: We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6-50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7-3·8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2-1·7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population. INTERPRETATION: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group. FUNDING: The Bill & Melinda Gates Foundation

Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus: a systematic analysis

Background: Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (<5 years) and older people (≥65 years). A global report of the monthly activity of these viruses is needed to inform public health strategies and programmes for their control. Methods: In this systematic analysis, we compiled data from a systematic literature review of studies published between Jan 1, 2000, and Dec 31, 2017; online datasets; and unpublished research data. Studies were eligible for inclusion if they reported laboratory-confirmed incidence data of human infection of influenza virus, respiratory syncytial virus, parainfluenza virus, or metapneumovirus, or a combination of these, for at least 12 consecutive months (or 52 weeks equivalent); stable testing practice throughout all years reported; virus results among residents in well-defined geographical locations; and aggregated virus results at least on a monthly basis. Data were extracted through a three-stage process, from which we calculated monthly annual average percentage (AAP) as the relative strength of virus activity. We defined duration of epidemics as the minimum number of months to account for 75% of annual positive samples, with each component month defined as an epidemic month. Furthermore, we modelled monthly AAP of influenza virus and respiratory syncytial virus using site-specific temperature and relative humidity for the prediction of local average epidemic months. We also predicted global epidemic months of influenza virus and respiratory syncytial virus on a 5° by 5° grid. The systematic review in this study is registered with PROSPERO, number CRD42018091628. Findings: We initally identified 37 335 eligible studies. Of 21 065 studies remaining after exclusion of duplicates, 1081 full-text articles were assessed for eligibility, of which 185 were identified as eligible. We included 246 sites for influenza virus, 183 sites for respiratory syncytial virus, 83 sites for parainfluenza virus, and 65 sites for metapneumovirus. Influenza virus had clear seasonal epidemics in winter months in most temperate sites but timing of epidemics was more variable and less seasonal with decreasing distance from the equator. Unlike influenza virus, respiratory syncytial virus had clear seasonal epidemics in both temperate and tropical regions, starting in late summer months in the tropics of each hemisphere, reaching most temperate sites in winter months. In most temperate sites, influenza virus epidemics occurred later than respiratory syncytial virus (by 0·3 months [95% CI −0·3 to 0·9]) while no clear temporal order was observed in the tropics. Parainfluenza virus epidemics were found mostly in spring and early summer months in each hemisphere. Metapneumovirus epidemics occurred in late winter and spring in most temperate sites but the timing of epidemics was more diverse in the tropics. Influenza virus epidemics had shorter duration (3·8 months [3·6 to 4·0]) in temperate sites and longer duration (5·2 months [4·9 to 5·5]) in the tropics. Duration of epidemics was similar across all sites for respiratory syncytial virus (4·6 months [4·3 to 4·8]), as it was for metapneumovirus (4·8 months [4·4 to 5·1]). By comparison, parainfluenza virus had longer duration of epidemics (6·3 months [6·0 to 6·7]). Our model had good predictability in the average epidemic months of influenza virus in temperate regions and respiratory syncytial virus in both temperate and tropical regions. Through leave-one-out cross validation, the overall prediction error in the onset of epidemics was within 1 month (influenza virus −0·2 months [−0·6 to 0·1]; respiratory syncytial virus 0·1 months [−0·2 to 0·4]). Interpretation: This study is the first to provide global representations of month-by-month activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus. Our model is helpful in predicting the local onset month of influenza virus and respiratory syncytial virus epidemics. The seasonality information has important implications for health services planning, the timing of respiratory syncytial virus passive prophylaxis, and the strategy of influenza virus and future respiratory syncytial virus vaccination. Funding: European Union Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU)

Antibiotic prophylaxis in the surgical management of miscarriage in low-income countries: a cost-effectiveness analysis of the AIMS trial

BackgroundThere is ongoing debate on the clinical benefits of antibiotic prophylaxis for reducing pelvic infection after miscarriage surgery. We aimed to study the cost-effectiveness of antibiotic prophylaxis in the surgical management of miscarriage in low-income countries.MethodsWe did an incremental cost-effectiveness analysis using data from 3412 women recruited to the AIMS trial, a randomised, double-blind, placebo-controlled trial designed to evaluate the effectiveness of antibiotic prophylaxis in the surgical management of miscarriage in Malawi, Pakistan, Tanzania, and Uganda. Economic evaluation was done from a health-care-provider perspective on the basis of the outcome of cost per pelvic infection avoided within 2 weeks of surgery. Pelvic infection was broadly defined by the presence of clinical features or the clinically identified need to administer antibiotics. We used non-parametric bootstrapping and multilevel random effects models to estimate incremental mean costs and outcomes. Decision uncertainty was shown via cost-effectiveness acceptability frontiers. The AIMS trial is registered with the ISRCTN registry, number ISRCTN97143849.FindingsBetween June 2, 2014, and April 26, 2017, 3412 women were assigned to receive either antibiotic prophylaxis (1705 [50%] of 3412) or placebo (1707 [50%] of 3412) in the AIMS trial. 158 (5%) of 3412 women developed pelvic infection within 2 weeks of surgery, of whom 68 (43%) were in the antibiotic prophylaxis group and 90 (57%) in the placebo group. There is 97–98% probability that antibiotic prophylaxis is a cost-effective intervention at expected thresholds of willingness-to-pay per additional pelvic infection avoided. In terms of post-surgery antibiotics, the antibiotic prophylaxis group was US$0·27 (95$1·4 million across the four participating countries and up to $8·5 million across the two regions of sub-Saharan Africa and south Asia.InterpretationAntibiotic prophylaxis is more effective and less expensive than no antibiotic prophylaxis. Policy makers in various settings should be confident that antibiotic prophylaxis in miscarriage surgery is cost-effective