Infant Immune Response Key to RSV vs. COVID Severity

Study finds differences in immune system reactions to respiratory viruses in young infants

Published on Feb. 26, 2026

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Young infants hospitalized with respiratory syncytial virus (RSV) often become much sicker compared to those infected with SARS-CoV-2, the virus that causes COVID-19. Scientists from St. Jude Children's Research Hospital and The Jackson Laboratory report that the two respiratory viruses trigger different immune responses, which might explain the different clinical outcomes and treatment needs.

Why it matters

Understanding the specific immune system differences between RSV and COVID-19 in infants is crucial for developing better treatment strategies. While both are respiratory viruses, RSV tends to cause more severe illness in young infants, despite COVID-19 also being a major threat. Identifying the underlying immune system factors could lead to more targeted therapies.

The details

The researchers compared the immune responses of infants hospitalized with either RSV or SARS-CoV-2 at a single-cell level, measuring proteins, genes and epigenetic signatures. They found that severe RSV was linked to unexpectedly low levels of systemic inflammation and a poorly coordinated early immune response, primarily by natural killer cells. This contrasted with the hyperinflammatory immune response seen in infants with SARS-CoV-2. The RSV response also showed lower interferon-gamma expression and reduced activity of key inflammatory signals that normally help fight infection.

  • The study was published on February 25, 2026.

The players

Octavio Ramilo

Co-corresponding author, chair of the St. Jude Department of Infectious Diseases.

Duygu Ucar

Co-corresponding author, Professor at The Jackson Laboratory.

Asunción Mejías

Co-first author, from the St. Jude Department of Infectious Diseases.

Asa Thibodeau

Co-first author, Associate Computational Scientist at The Jackson Laboratory.

Jacques Banchereau

Co-corresponding author, from The Jackson Laboratory.

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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 very different types of immune dysregulation in young infants.”

— Octavio Ramilo, Chair, St. Jude Department of Infectious Diseases (Mirage News)

“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.”

— Duygu Ucar, Professor, The Jackson Laboratory (Mirage News)

“Most strikingly, we saw infants with RSV had significantly fewer numbers of natural killer cells, compared to those with SARS-CoV-2 infections.”

— Asunción Mejías, Co-first author, St. Jude Department of Infectious Diseases (Mirage News)

“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.”

— Asa Thibodeau, Associate Computational Scientist, The Jackson Laboratory (Mirage News)

What’s next

The study's results and methodology provide a blueprint for better understanding infant immunity in general, which could lead to improved treatments and outcomes for young children hospitalized with respiratory viruses.

The takeaway

This study highlights the critical differences in how the infant immune system responds to RSV versus SARS-CoV-2, which helps explain the more severe illness often seen with RSV infections. Understanding these immune system variations is key to developing targeted therapies and improving clinical outcomes for infants with respiratory viral infections.