Preterm infants are at disproportionately high risk of serious illness caused by respiratory syncytial virus (RSV) – a threat that continues into their second year of life, research suggests.

The finding implies that interventions to prevent and manage RSV-related infections may need to be extended for this group, particularly in low- and middle-income countries, which bear the greatest burden of severe disease.

In total, preterm infants accounted for a quarter of RSV-associated acute lower respiratory hospitalisations in all infants.

RSV is a leading cause of lower respiratory tract infections in children under the age of five, responsible for some 3.6 million hospital admissions and 101,400 deaths among this age group during 2019 alone.

Children in low- and middle-income countries are disproportionately affected, and these outbreaks can place considerable pressure on health care systems during winter and early spring, when other respiratory infections such as influenza are also at their peak.

While preterm infants were previously known to be at elevated risk – due to their less mature immune systems, smaller airways and other factors – the extent of RSV-related disease burden in this group was unclear. Researchers also wanted to learn more about specific factors that increase individuals’ risk of severe illness – particularly as vaccines and other preventative treatments against RSV are beginning to be rolled out.

To better understand these risks and generate data that could help to inform policy makers, Xing Wang and Yu Li at Nanjing Medical University in China and their colleagues systematically analysed data from 64 previously published studies on RSV-related illness and deaths in preterm infants and young children, including individual-level data shared by the authors of 17 of these papers.

The research, published in The Lancet, found that early preterm infants (those born before 32 weeks of gestation) had higher rates of RSV-associated lung infections and hospitalisations than the general infant population – and that this higher risk of hospitalisation persisted into their second year of life. Those with existing underlying heart or lung disease were at even higher risk.

Infants born between 32 weeks and 37 weeks of gestation also had higher rates of hospitalisation from RSV during their first six months of life compared to those born at term. In total, preterm infants accounted for a quarter of RSV-associated acute lower respiratory hospitalisations in all infants.

Writing in an associated commentary,Dr  David Torres-Fernandez and Dr Quique Bassat at the University of Barcelona in Spain described this as an “unacceptably high global burden” and stressed the need for further research – particularly in the context of low- and middle-income countries. The study found that 93% of RSV-associated episodes, 92% of hospitalisations and 89% of in-hospital deaths occurred in these settings.

They also pointed out that the current research and development of pharmaceutical interventions against RSV are still biased towards their use in high-income countries. For instance, various countries have approved a monoclonal antibody-based injection that is designed to protect infants against hospitalisation during their first RSV season, including preterm infants.

A maternal vaccine against RSV – given to people who are 32 to 36 weeks pregnant to protect their infants from birth – has also been approved in some countries, but it hasn’t yet received World Health Organization prequalification, which is needed for United Nations agencies to procure the vaccine in partnership with Gavi, the Vaccine Alliance and eligible countries.

“However, the current prohibitive costs and associated production and distribution challenges of these treatments hinder their potential implementation in low- and middle-income countries, where they could have more impact and benefit,” Torres-Fernandez and Bassat said. “It is perhaps the moment to explore, similar to what has been done in the field of antimalarials and antiretrovirals, a tiered pricing strategy that could foster affordability among those most in need but with fewer resources.”

Wang and Li also pointed out that the phase 3 trial results of the maternal RSV vaccine were not powered to estimate its efficacy for preterm infants. “As governments begin to consider including RSV vaccines in national immunisation programmes, understanding the global disease burden of, and the risk factors for, RSV-associated acute lower respiratory infections in preterm infants and young children is essential for the design of an optimal RSV prophylaxis strategy,” they said.