A U.S. study has provided evidence as to why steroids may be useful to treat certain respiratory viruses in babies but not others.
The findings revealed different immune signatures for respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which could help guide treatment.
Interferon activation was common with both infections, the researchers report in Science Translational Medicine.
But inflammation emerged as a critical point of divergence, potentially explaining why anti-inflammatories are effective against COVID-19 but not RSV.
“Our study provides insights that may inform clinical decision making regarding the management of these viral infections in early life,” reported Asa Thibodeau, PhD, from the Jackson Laboratory for Genomic Medicine in Connecticut.
Babies are prone to respiratory viruses, and RSV is a leading cause of hospitalization and mortality during the first year of life.
In contrast, SARS-CoV-2 tends to be milder in this age group with typically lower morbidity.
The different clinical presentations of the two viral infections in infants led the researchers to investigate immune responses in babies to try and improve both prevention and treatment.
The team collected blood samples within 24 hours of hospitalization from 19 babies with RSV and 30 with SARS-CoV-2 with a range of disease severities and compared these with 17 healthy control babies.
All were similarly aged, at a median of 2.3 months.
The samples were analyzed using a mixture of cytokine profiling, single-cell transcriptomics, and epigenomics.
Both viruses triggered similar signatures in the expression of interferon-stimulated genes, a hallmark of antiviral immunity, but had different effects on individual immune cell types.
Specifically, they differed in inflammatory responses, epigenetic remodeling, NK cell responses, and responses by subsets of adaptive immune cells.
RSV infections were associated with higher counts of memory T cell and memory regulatory T cells in the blood. Babies with severe RSV infections had reduced levels of natural killer cells in the blood and lower expression of an RNA called IFNG from natural killer cells.
In contrast, SARS-CoV-2 induced strong proinflammatory responses, including elevated serum concentrations of tumor necrosis factor and activation of nuclear factor ÎşB pathway genes and loci in peripheral blood mononuclear cells.
“Together, these findings highlight disease-specific immune dysregulation and highlight the need for tailored therapies for these respiratory viruses,” the researchers concluded.
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