RSV vs. COVID-19: Why Infants Get Sicker with RSV – and What It Means for Treatment
Young infants hospitalized with respiratory syncytial virus (RSV) often experience more severe illness than those with COVID-19. New research from St. Jude Children’s Research Hospital and The Jackson Laboratory reveals that these differing outcomes aren’t simply due to the viruses themselves, but to fundamentally different immune responses in infants. Published in Science Translational Medicine on February 25, 2026, the study offers crucial insights into how to better protect vulnerable babies.
The Puzzle of RSV Severity
During the COVID-19 pandemic, doctors noticed a concerning trend: infants admitted to hospitals with RSV infections frequently exhibited more severe symptoms than those hospitalized with SARS-CoV-2, despite both being respiratory RNA viruses. This observation prompted researchers to investigate the underlying immunological mechanisms driving these disparities.
A Single-Cell View of Immune Responses
The research team compared the immune responses of infants hospitalized with RSV, those hospitalized with SARS-CoV-2, and healthy infants at the single-cell level. By analyzing proteins, genes, and epigenetic signatures in blood samples, they pinpointed the specific immune cells and signals responsible for the observed differences. The study included 19 infants with RSV, 30 with SARS-CoV-2, and 17 healthy infants, most around two months aged.
RSV: A Surprisingly Weak Immune Response
The findings were unexpected. Severe RSV in infants was linked to surprisingly low levels of systemic inflammation and a poorly coordinated early immune response, particularly from natural killer (NK) cells. This contrasts sharply with the hyperinflammatory immune response seen in infants with SARS-CoV-2 infection.
“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,” explained Dr. Octavio Ramilo, chair of the Department of Infectious Diseases at St. Jude.
Epigenetic Reprogramming by RSV
Further analysis revealed that RSV appears to reprogram parts of the infant immune system at the epigenetic level – altering how genes are turned on or off. This epigenetic shift may explain why RSV can lead to more severe disease and potentially influence future immune responses.
“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 Dr. Duygu Ucar, Professor at The Jackson Laboratory.
Implications for Treatment: Why Steroids Don’t Work for RSV
The study has direct clinical implications. Because RSV already suppresses the immune system, administering anti-inflammatory treatments like steroids – which can be helpful for severe COVID-19 – may actually be harmful in RSV cases. Researchers found that infants with RSV had significantly fewer natural killer cells and reduced interferon-gamma production, a key molecule for fighting viruses.
“One very practical implication of our work is that we should not routinely provide steroids to infants with RSV,” stated Dr. Asunción Mejías, of St. Jude Department of Infectious Diseases.
The Bigger Picture: Infant Immunity and Global Health
RSV remains a leading cause of infant hospitalization and the second leading cause of infant mortality worldwide. This research provides a blueprint for better understanding infant immunity in general, particularly during the critical early months of life before vaccines are administered.
“Globally, five million children die before the age of 5, half occurring in the first months of life due to infection, before vaccines are given,” Dr. Ramilo emphasized. “With the tools we have developed, we can start to uncover what’s happening in that early immunological window to begin improving those odds.”
Pro Tip
Protecting infants from RSV involves more than just avoiding sick contacts. Discuss preventative options, like nirsevimab, with your pediatrician, especially if your baby is at high risk.
FAQ: RSV and Infant Immunity
Q: Why are infants more severely affected by RSV than adults?
A: Infants have immature immune systems that respond differently to RSV compared to adults, leading to a less effective initial response.
Q: Does this research change how RSV is treated?
A: It suggests that anti-inflammatory treatments like steroids, which are sometimes used for COVID-19, may not be beneficial and could even be harmful for infants with RSV.
Q: What is nirsevimab and how does it help?
A: Nirsevimab is a long-acting monoclonal antibody that provides protection against RSV. This proves recommended by the CDC to prevent severe RSV-related disease.
Q: What role do natural killer cells play in fighting RSV?
A: The study found that infants with severe RSV had fewer natural killer cells, which are crucial for fighting viral infections.
Did you grasp? RSV can cause bronchiolitis and pneumonia in infants, leading to breathing difficulties and hospitalization.
Learn more about RSV prevention and treatment options by consulting with your healthcare provider and exploring resources from organizations like the CDC and St. Jude Children’s Research Hospital.
