Differing Immune Responses May Explain Severe RSV in Infants

New research reveals fundamental differences in how infants' immune systems react to RSV versus SARS-CoV-2.

Feb. 25, 2026 at 7:52pm

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A study from St. Jude Children's Research Hospital and The Jackson Laboratory found that infants hospitalized with respiratory syncytial virus (RSV) often exhibit more severe symptoms than those with COVID-19, despite both being respiratory RNA viruses. The researchers compared the immune responses of infants with RSV, SARS-CoV-2, and healthy infants, discovering that severe RSV is linked to surprisingly low levels of systemic inflammation and a poorly coordinated early immune response, particularly from natural killer cells. This contrasts with the hyperinflammatory response seen in infants with SARS-CoV-2.

Why it matters

RSV remains a leading cause of infant hospitalization and the second leading cause of infant mortality worldwide. Understanding the underlying immunological mechanisms driving the differing outcomes between RSV and SARS-CoV-2 in infants is crucial for improving treatment and prevention strategies.

The details

The research team analyzed proteins, genes, and epigenetic signatures in blood samples from 19 infants with RSV, 30 with SARS-CoV-2, and 17 healthy infants. They found that severe RSV was associated with low levels of systemic inflammation and a poorly coordinated early immune response, particularly from natural killer cells. In contrast, infants with SARS-CoV-2 exhibited a hyperinflammatory immune response. Further analysis revealed that RSV appears to reprogram parts of the infant immune system at the epigenetic level, which may explain the more severe disease and influence future immune responses.

  • The study was published in Science Translational Medicine on February 25, 2026.

The players

Dr. Octavio Ramilo

Chair of the Department of Infectious Diseases at St. Jude Children's Research Hospital.

Dr. Duygu Ucar

Professor at The Jackson Laboratory.

Dr. Asunción Mejías

Of the St. Jude Department of Infectious Diseases.

St. Jude Children's Research Hospital

A leading pediatric research hospital located in Memphis, Tennessee.

The Jackson Laboratory

A nonprofit biomedical research institution focused on the genetic basis of disease.

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What they’re saying

“We showed, for the first time, that two similar respiratory viruses, RSV and SARS-CoV-2, cause extremely different types of immune dysregulation in young infants.”

— Dr. Octavio Ramilo, Chair of the Department of Infectious Diseases at St. Jude

“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.”

— Dr. Duygu Ucar, Professor at The Jackson Laboratory

“One very practical implication of our work is that we should not routinely provide steroids to infants with RSV.”

— Dr. Asunción Mejías, Of the St. Jude Department of Infectious Diseases

What’s next

The researchers plan to further investigate the epigenetic reprogramming of the infant immune system by RSV and explore new treatment approaches that target the specific immune dysregulation seen in severe RSV cases.

The takeaway

This research provides crucial insights into the fundamental differences in how infant immune systems respond to RSV versus SARS-CoV-2, which could lead to improved prevention and treatment strategies for this leading cause of infant hospitalization and mortality worldwide.