A shocking revelation has emerged from a recent study, highlighting the stark contrast between the immune responses triggered by Respiratory Syncytial Virus (RSV) and SARS-CoV-2 in infants. Despite both being respiratory viruses, the clinical outcomes and required treatment strategies differ significantly.
During the COVID-19 pandemic, doctors noticed a curious trend: infants hospitalized with RSV often exhibited more severe symptoms than those with SARS-CoV-2. To unravel this mystery, researchers from St. Jude Children's Research Hospital and The Jackson Laboratory (JAX) delved into the immune responses of these infants at a single-cell level.
But here's where it gets controversial...
The study, published in Science Translational Medicine, revealed that RSV and SARS-CoV-2 induce distinct immune dysregulations in young infants. Dr. Octavio Ramilo, co-corresponding author and chair of the St. Jude Department of Infectious Diseases, emphasized, "The host response differs depending on the infecting virus at the chemical, cellular, and even epigenetic level."
One of the key findings was the unexpectedly low levels of systemic inflammation and a poorly coordinated early immune response in infants with severe RSV. This was primarily attributed to the activity of natural killer cells, a specialized set of immune cells. In contrast, infants with SARS-CoV-2 infection exhibited a hyperinflammatory immune response profile.
"What surprised us most was the stark difference in immune gene regulation," said co-corresponding author Dr. Duygu Ucar, a professor at JAX. "RSV appears to reprogram parts of the infant immune system at the epigenetic level, essentially flipping molecular switches that control gene activation."
Dr. Ucar further explained, "These epigenetic changes may contribute to the severity of RSV and potentially impact the immune system's future responses."
To uncover these differences, the researchers compared immune cells and proteins from blood samples of 19 infants hospitalized with RSV, 30 with SARS-CoV-2, and 17 healthy age-matched infants, most of whom were around 2 months old.
A comprehensive single-cell analysis revealed that while both viruses induce a similar rise in most interferons, antiviral molecules that combat viruses, there were drastic differences in other aspects.
"Most strikingly, we found that infants with RSV had significantly fewer natural killer cells compared to those with SARS-CoV-2 infections," said co-first author Dr. Asunción Mejías, from the St. Jude Department of Infectious Diseases. "These cells also produced less interferon-gamma, a crucial molecule in viral defense, and this was strongly correlated with disease severity."
And this is the part most people miss...
The RSV response was characterized by lower interferon-gamma expression and reduced activity of key inflammatory signals (IL-1B, NF-KB), which normally aid in fighting infection. In contrast, SARS-CoV-2 generally causes significant immune dysregulation across multiple cell types, with a notable increase in pro-inflammatory molecules like TNF alpha and NF-κB activity.
This contrast in immune responses provides valuable clinical guidance. Dr. Mejías emphasized, "Our work suggests that steroids, which suppress immunity, should not be routinely given to infants with RSV. RSV already suppresses the immune system, and adding steroids may further impair the natural killer cell response, which is crucial in combating the virus."
RSV remains the primary cause of infant hospitalizations and the second leading cause of infant mortality worldwide. This study's methodology and results offer a blueprint for a better understanding of infant immunity in general.
"Globally, five million children die before the age of 5, with half of these deaths occurring in the first months of life due to infection, before vaccines can be administered," Dr. Ramilo noted. "With our advanced tools, we can now begin to uncover the early immunological processes and improve the odds for these vulnerable infants."
This study was supported by grants from the National Institutes of Health and the American Lebanese Syrian Associated Charities (ALSAC), the fundraising organization of St. Jude.
