Respiratory syncytial virus (RSV) caused more than 100,000 deaths in children under age 5 years globally in 2019, according to an analysis published online May 19 in The Lancet.
Researchers, led by You Li, PhD, of the School of Public Health, Nanjing Medical University in Nanjing, China, found that nearly half of those (more than 45,000) occurred in children younger than 6 months old.
They estimated that RSV causes 1 in 50 deaths among children under 5 years old, and 1 in 28 deaths in children under 6 months old.
Additionally, RSV is responsible for an estimated 3.6 million hospital admissions globally each year, according to the report.
This analysis is the first to sift RSV disease burden into narrow age brackets, the authors say.
The numbers highlight that almost all of the deaths (97%) were in low- and middle-income countries.
Messages for Prevention
Tina Hartert, MD, MPH, a professor in the Division of Allergy, Pulmonary, and Critical Care Medicine at Vanderbilt School of Medicine, in Nashville, Tennessee, who was not part of the study, wrote in an invited commentary that these findings will be important in RSV prevention.
Among the most notable findings, she writes, is the heavy mortality in the 0- to 6-month age group, which she notes is “the age group targeted by vaccination during pregnancy and birth-dose immunoprophylaxis.”
Hartert, who coauthored the commentary with Justin R. Ortiz, MD, MS, with the Center for Vaccine Development and Global Health, University of Maryland School of Medicine in Baltimore, told Medscape Medical News, “RSV is a respiratory virus that infects nearly every child by the time they are 2 to 3 years of age, with severe infection and death most common in the youngest infants. Vaccines that prevent the most severe infections in these young infants will likely be one of the best ways to prevent these severe infections and death.”
Though the authors found most deaths occur in low- and middle-income countries, RSV is one of the most common reasons for infant hospitalization in the US and affects 1% to 3% of infants, half of whom are full-term and otherwise healthy, Hartert said.
It is also one of the most common causes of infant lower respiratory tract infection in young children in the US, she said, and it causes the most severe disease at the age extremes, with older adults experiencing significant morbidity with RSV.
Li told Medscape Medical News that although the team did not focus on reporting country-specific estimates in this work, their previous work, published last year, resulted in estimates of 98,000 to 155,000 RSV-related hospitalizations in children under 5 years old in the US in 2019. Between 65,000 and 86,000 were in infants less than 1 year old.
Currently, he said, the only available RSV prophylaxis is palivizumab (Synagis), which is expensive and given only to high-risk infants in high-income countries, including the US.
“There have been a number of promising RSV prophylactic products including maternal vaccine and monoclonal antibodies that have the potential for targeting the general infant population — not just high-risk infants — in late-phase clinical trials,” he said. “Our estimates of RSV-related disease burden will help anticipate the impact of future RSV immunization programs.”
Pandemic Changed Patterns
This research was completed before the COVID-19 pandemic, and it is not yet known how that could affect RSV disease burden long term.
However, Hartert says, RSV circulation has been significantly changed during the pandemic, both in intensity and timing, likely because of a combination of COVID and the public health preventive measures.
“As people return to normal activities and the public health measures put in place to stop the spread of COVID are eased, we are likely to see increases in circulation of RSV and return to its circulation during the winter months — typically similar to circulation of flu — from November through March in temperate climates in the northern hemisphere,” she said.
A coauthor of the paper, Harish Nair, PhD, with the Centre for Global Health, Usher Institute, University of Edinburgh in Edinburgh, Scotland, said in a press release that their findings have particular significance as COVID restrictions ease around the globe.
“[T]he 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),” Nair writes.
Most Deaths Occurring Outside Hospitals
A challenge in reducing the deaths in those 5 years old and younger is that most (76%) of deaths are happening in the community outside hospitals.
The authors write, “For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community.”
The percentage dying outside hospitals is even larger (81%) in low- to middle-income countries.
This work built on a previous review by the team that analyzed 317 studies. They updated their search with 113 new eligible studies and unpublished data from 51 papers published between January 1, 2017, and December 31, 2020.
The authors acknowledged some limitations, including variations in study settings and in definitions for acute lower respiratory infection, healthcare access, and eligibility for RSV testing.
The study was funded by EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU). Li reported grants from Wellcome Trust and WHO outside the submitted work. Hartert, Ortiz, and Nair have disclosed no relevant financial relationships.
Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, and Nurse.com, and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick.