Peer-reviewed/Literature review and Modelling/People
- Acute lower respiratory infection caused by Respiratory Syncytial Virus (RSV) contributes substantially to the global mortality burden in children, with RSV estimated to cause one in 50 deaths among children under five, and one in 28 deaths among children under six months.
- More than 100,000 deaths in children under five were attributable to RSV in 2019, with nearly half of these (more than 45,000) occurring in children younger than six months old. RSV is responsible for an estimated 3.6 million hospital admissions every year.
- 97% of childhood deaths caused by RSV were in low- and middle-income countries. The authors say these findings highlight the urgent need to develop effective RSV vaccines and strategies that prioritise the most vulnerable groups, such as children younger than six months old through passive immunisation (i.e., vaccinating during pregnancy)
A new study published in The Lancet estimates that RSV-attributable acute lower respiratory infection was responsible for more than 100,000 deaths in children under five across the globe in 2019. The study is the first to examine RSV disease burden in narrow age brackets, reporting that there were over 45,000 deaths in infants under six months old in 2019, with one in five of the total global cases of RSV occurring in this age group.
“RSV is the predominant cause of acute lower respiratory infection in young children and our updated estimates reveal that children six months and younger are particularly vulnerable, especially with cases surging as COVID-19 restrictions are easing around the world and majority of the young children born in the last 2 years have never been exposed to RSV (and therefore have no immunity against this virus). With numerous RSV vaccine candidates in the pipeline, our estimates by narrower age ranges help to identify groups that should be prioritised, including pregnant people, so that children in the youngest age groups can be protected, similarly to current strategies which offer vaccines for whooping cough, typhoid, and tetanus to pregnant people,” says Harish Nair, co-author of the paper, University of Edinburgh, UK. 
This new study’s findings are broadly consistent with previous estimates from a 2015 study, which placed the number of annual cases of RSV in children up to five years old at 33.1 million, resulting in a total of 118,200 overall deaths . However, these updated calculations of RSV mortality on global, regional, and national levels for the year 2019 include modelling data from over a hundred new studies, allowing researchers to provide estimates for narrower age groups – including from 28 days to six months old, which is known to be the age range with the highest RSV fatality rate – and community mortality rates (i.e., deaths that did not occur in a hospital).
Across the globe in 2019, there were 33 million RSV-associated acute lower respiratory infection episodes in children under five years old, leading to 3.6 million hospital admissions, 26,300 in-hospital deaths and 101,400 RSV-attributable deaths overall (including community deaths). This accounts for one in 50, or 2% of annual deaths from any cause in this age range.
For children under six months old, there were 6.6 million RSV-associated acute lower respiratory infection episodes globally in 2019. There were 1.4 million hospital admissions, 13,300 hospital deaths and 45,700 overall deaths attributable to RSV in this age range, accounting for one in 50, or 2.1% of annual deaths from any cause.
Based on estimates of in-hospital versus overall RSV mortality rates, globally only 26%, or approximately one in four RSV-associated deaths occur in a hospital. This is particularly apparent in low- and middle- income countries, where the in-hospital case-to-fatality ratio for children under five is 1.4%, compared to 0.1% in high income countries. Overall, 97% of RSV deaths in children under five occurred in low- and middle-income countries.
“Our study estimates that three-quarters of RSVs deaths are happening outside of a hospital setting. This gap is even greater in LMICs, especially in children under six months old, where more than 80% of deaths are occurring in the community. This reflects the fact that access and availability to hospital care are still limited in these regions. Early identification of cases in the community and referral for hospital admission of sick children (particularly those with low oxygen saturation in peripheral blood), and universal effective and affordable immunisation programmes will be vital going forward,” says Xin Wang, co-author of the study, Nanjing Medical University, China and University of Edinburgh, UK. 
The authors acknowledge some limitations with this study. Variations in factors such as study setting, exact case definition for acute lower respiratory infection (ALRI) , health-care access and seeking behaviour, and eligibility for RSV testing could affect estimates of mortality figures produced in the modelling. The breakdown by age bands was also limited by the data available for the study. In addition, all data were collected before the COVID-19 pandemic; it is unknown how the COVID-19 pandemic could affect RSV disease burden in the long term.
Writing in a linked comment, Tina Hartert, Vanderbilt School of Medicine, USA, who wasn’t involved in the research, said: “The influence of these data cannot be understated. There is a substantial RSV ALRI burden during the newborn period in LMICs, highlighting the potential for passive immunization strategies to meaningfully impact child health… Policy makers will benchmark benefits of RSV prevention against other priority public health interventions. Accurate estimates of prevention impact are critical to demonstrating the investment case for RSV prevention.”
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Method of Research
Subject of Research
Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis
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YL reports grants from Wellcome Trust and WHO outside the submitted work. MTC reports grants from the Bill & Melinda Gates Foundation related to the submitted work, grants from MITS Surveillance Alliance, and support for attending the RSVVW meeting from ReSViNET outside the submitted work. SAM reports grants from Pfizer, Minervax, GSK, the Gates Foundation, and South African Medical Research Council; honoraria from the Gates Foundation; and participation on data safety monitoring boards for PATH and CAPRISA, outside the submitted work. SBO reports grants from the Gates Foundation outside the submitted work. EAFS reports grants, personal fees, and travel fees from AstraZeneca, Merck, Regeneron, Pfizer, and Roche; consultation, lecture fees, travel support, and data and safety monitoring board fees from AbbVie; data and safety monitoring board fees from GSK; consultation fees from Alere; grants from Johnson & Johnson; and grants and travel support from Novavax outside the submitted work. HC reports grants from the Gates Foundation outside the submitted work. AGo reports grants from the National Institute of Allergy and Infectious Diseases and Centers for Disease Control and Prevention (CDC) related to the submitted work and participation on an advisory board for Janssen outside the submitted work. TH reports personal fees from Janssen and Sanofi Pasteur outside the submitted work. AK reports grants from CDC and honoraria from CDC and WHO outside the submitted work. AM-I reports grants from FISABIO-Public Health, Sanofi Pasteur, and CIBER-ESP (ISCIII) related to the submitted work, honoraria from MSD as a speaker in a vaccine research course, and travel grants for attending meetings sponsored by Sanofi, outside the submitted work. HCM reports grants from National Health and Medical Research Council related to the submitted work and honoraria from MSD for participation on an expert input forum outside the submitted work. DJN reports grants from Wellcome Trust related to the submitted work. EO reports receipt of PhD scholarship from DAAD (German Academic Exchange Service) Government of Ghana scholarship outside the submitted work. CR reports grants from CDC in collaboration with US Naval Medical Research Unit No6 related to the submitted work and grants from South America Influenza Initiative outside the submitted work. AS reports grants from University of Colorado outside the submitted work. RS reports grants from Merck outside the submitted work. SKS reports salaries from GSK for working on the data abstraction, leading the prospective cohort study from which the data were abstracted, and for providing input for the manuscript development related to the submitted work and stock in GSK outside the submitted work. AvG reports grants from CDC outside the submitted work. DW reports grants from Murdoch Children’s Research Institute related to thesubmitted work and honoraria from MSD for participation on an expertninput forum outside the submitted work. L-MY reports grants from Japan Agency for Medical Research and Development related to the submitted work and honoraria for a lecture from MSD KK. HJZ reports grants from the Gates Foundation, South African Medical Research Council, National Institutes for Health, and AstraZeneca and participation on WHO Technical Advisory Group with no payment, outside the submitted work. HN reports grants from the Innovative Medicines Initiative related to the submitted work and consulting fees from the Gates Foundation, Pfizer, and Sanofi; honoraria from AbbVie; support from Sanofi for attending meetings; and participation on advisory boards from Sanofi, Janssen, Novavax, Reviral, Resvinet, and WHO outside the submitted work.