RSV Infection in Infancy Linked to Later Asthma

Children who do not contract respiratory syncytial virus (RSV) in their first year of life may be less likely to develop asthma later on, the prospective U.S.-based INSPIRE study showed.

Those who dodged RSV infection as infants were significantly less likely to have asthma at 5-year follow-up (adjusted RR 0.74, 95% CI 0.58-0.94, P=0.014), with an absolute rate of 16% by that point versus 21% for those who had contracted RSV in infancy, reported Tina Hartert, MD, of Vanderbilt University Medical Center in Nashville, Tennessee, and coauthors.

"In this large, population-based birth cohort of healthy infants born at term, we showed that infants without RSV infection have a substantially reduced risk of developing childhood asthma compared with infants with RSV infection," the group wrote in The Lancet. "To our knowledge, INSPIRE is the first study specifically designed to test the hypothesis that not being infected with RSV during infancy decreases the risk of childhood asthma."

Researchers estimated that 15% of current 5-year asthma cases could be reduced by successfully preventing RSV in infants under a year old.

To that end, FDA reviewers are currently considering two products that have demonstrated efficacy against severe RSV illness in infants: an investigational bivalent RSV prefusion F protein-based vaccine (administered during the mother's third trimester of pregnancy) and the long-acting monoclonal antibody nirsevimab for newborns.

A typical RSV season lasts from fall through early spring. According to CDC estimates, approximately 100 to 300 U.S. children under the age of 5 die each year due to RSV-associated illness, and the virus is responsible for over 2 million outpatient visits and up to 80,000 hospitalizations among this group annually.

The COVID pandemic was associated with a period of low RSV exposure due to strict public health interventions. Since its resurgence, however, RSV infections have resulted in disproportionately more children getting hospitalized, as previously observed during the 2021-2022 season in a study from Denmark.

"The epidemiology of RSV is continuously changing and updated estimates of the burden of disease are needed to prioritize research findings, inform public health policy, and adequately design and power experimental studies of early-life RSV immunoprophylaxis programs," Hartert and colleagues wrote.

Their study included 1,946 infants (48% girls, median age 55 days) enrolled from 11 pediatric practices in Tennessee. All had been born between June and December 2012 and June to December 2013.

RSV infection was ascertained via passive and active surveillance. Parents were contacted regularly and children underwent nasal washes and blood sampling at some healthcare encounters.

Of the 1,741 participants with available RSV infection data, 54% had been infected during their first year of life. The infected group differed from their peers in terms of certain baseline characteristics such as race and ethnicity and a greater likelihood of birth by cesarean section.

Study authors found that the secondary outcome of recurrent wheeze was also less likely among children with no RSV infection during infancy, significantly so through year 1 and 2.

Among patients who had received blood-specific immunoglobulin E (IgE) testing at 3 years, children with no prior RSV infection tended to have less non-atopic asthma but no difference in atopic asthma.

"It is important to recognize that although our findings suggest a causal association, because of the observational design, our study can never definitively establish causality," Hartert's group cautioned. "Instead, our results highlight the need for long-term follow-up of common respiratory outcomes among children participating in ongoing and future clinical trials of agents for RSV immunoprophylaxis."

The researchers also acknowledged possible misclassification of RSV in some patients, where infants that did have RSV were not officially diagnosed, as well as a lack of applicability to others outside the study population.

"Most convincing evidence for causality should come from efficacy trials which are large enough to show that preventing RSV infection (by immunoprophylaxis or maternal vaccination) results in a decrease in childhood asthma," suggested epidemiologist Marie-Noëlle Billard, MS, and pediatric infectious disease specialist Louis Bont, MD, PhD, of the University Medical Center in Utrecht, the Netherlands.

"Thus, we strongly support the call of the authors for including asthma endpoints in RSV efficacy trials. Showing efficacy against childhood asthma would increase the public health interest of these strategies," the pair wrote in an accompanying commentary.

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