New research examining infant immune responses to respiratory viruses may help explain why respiratory syncytial virus (RSV) often causes more severe illness than SARS-CoV-2. The study, published in Science Translational Medicine, was conducted by scientists at St. Jude Children’s Research Hospital and Farmington-based The Jackson Laboratory (JAX).
Although both RSV and SARS-CoV-2 are respiratory RNA viruses, physicians have observed that infants hospitalized with RSV frequently develop more serious complications. To better understand this difference, researchers compared blood samples from infants hospitalized with each infection alongside samples from healthy infants.
The analysis revealed that RSV infections were associated with lower systemic inflammation and a less coordinated early immune response. Infants with RSV also had fewer natural killer cells and reduced interferon-gamma activity, both of which play important roles in antiviral defense. By contrast, SARS-CoV-2 infections produced a more inflammatory immune profile.
“We showed, for the first time, that two similar respiratory viruses, RSV and SARS-CoV-2, cause very different types of immune dysregulation in young infants,” said Octavio Ramilo, MD, St. Jude Children’s Research Hospital.
“What surprised us most was that the antiviral responses looked similar at first glance, but when we examined how immune genes were regulated, we saw striking differences,” said Duygu Ucar, PhD, The Jackson Laboratory. “RSV appears to reprogram parts of the infant immune system at the epigenetic level; which are molecular switches that control how genes are turned on or off.”
“These changes may help explain why RSV can lead to more severe disease and possibly influence how the immune system responds in the future,” Ucar concluded.
“Most strikingly, we saw infants with RSV had significantly fewer numbers of natural killer cells, compared to those with SARS-CoV-2 infections,” said Asunción Mejías, MD, PhD, St. Jude Children’s Research Hospital. “In those patients, these cells also made less interferon-gamma, a key molecule to defend against viruses, which was strongly correlated with disease severity.”
“Integrating single cell technologies using advanced computational methods enabled us to not only identify immune response signatures in specific immune cell types but also associate gene expression with potential epigenetic regulators,” said Asa Thibodeau, PhD, The Jackson Laboratory. “Understanding immune differences at the transcriptional and epigenetic level will guide future studies and better treatments.”
