RSV More Severe Than COVID-19 in Infants, Study Reveals Distinct Immune Responses
A groundbreaking study by scientists from St. Jude Children's Research Hospital and The Jackson Laboratory (JAX) has found that young infants hospitalized with respiratory syncytial virus (RSV) often become significantly sicker than those infected with SARS-CoV-2, the virus causing COVID-19. Published in Science Translational Medicine, the research indicates that these two common respiratory viruses elicit vastly different immune responses in infants.
These distinctions may account for the varying clinical outcomes observed and suggest different strategies for treatment.
Unpacking the Immune Response: Study Design
During the COVID-19 pandemic, physicians noted that infants admitted with RSV infection frequently exhibited more severe symptoms than those hospitalized with SARS-CoV-2, despite both being respiratory RNA viruses. To investigate this critical observation, researchers embarked on a comparative study.
The team meticulously compared the immune responses of 19 infants hospitalized with RSV, 30 with SARS-CoV-2, and 17 healthy, age-matched infants. Most participants in the study were approximately two months old. Utilizing advanced single-cell analysis, alongside measurements of proteins, genes, and epigenetic signatures in blood samples, the study aimed to identify specific immune cells and signals contributing to these observed differences.
RSV Triggers Poorly Coordinated Immune Response, While SARS-CoV-2 Induces Hyperinflammation
The study revealed starkly distinct immune response profiles. Severe RSV in infants was associated with lower levels of systemic inflammation and a poorly coordinated early immune response, primarily involving natural killer cells. This stands in sharp contrast to the hyperinflammatory immune response observed in infants with SARS-CoV-2 infection.
"While antiviral responses initially appeared similar, significant differences emerged in how immune genes were regulated," noted co-corresponding author Duygu Ucar, PhD, from JAX.
RSV appears to epigenetically reprogram parts of the infant immune system, influencing gene activation and deactivation. These profound changes may contribute to RSV's severity and potentially impact future immune responses.
Specifically, infants with RSV showed significantly fewer natural killer cells compared to those with SARS-CoV-2 infections. These crucial cells also produced less interferon-gamma, a critical antiviral molecule, with its reduction strongly correlating with disease severity. The RSV response also featured lower interferon-gamma expression and reduced activity of key inflammatory signals, including IL-1B and NF-KB.
Conversely, SARS-CoV-2 typically induced significant immune dysregulation across multiple cell types. Researchers observed a notable increase in several pro-inflammatory molecules, such as TNF alpha and NF-κB activity, in these infants.
Tailored Treatments: Implications for Clinical Care
The findings carry practical implications for treatment approaches. The hyperinflammatory response characteristic of SARS-CoV-2 may explain why anti-inflammatory treatments like steroids benefit some severe COVID-19 patients.
In stark contrast, steroids have not been effective for RSV patients and could potentially be harmful, as RSV itself is immunosuppressive.
Co-first author Asunción Mejías, MD, PhD, MsCS, from St. Jude, emphasized, "routinely administering steroids to infants with RSV is not advisable, as it could further impair the natural killer cell response."
RSV remains a leading cause of infant hospitalizations and the second-highest cause of infant mortality globally. The study’s results and methodology offer a robust framework for enhancing the understanding of infant immunity. Co-corresponding author Octavio Ramilo, MD, St. Jude Department of Infectious Diseases chair, highlighted the potential of these tools to uncover early immunological processes and improve outcomes for the millions of children who die before age five due to infection.