When defense backfires: inflammatory determinants of RSV-induced disease severity

Respiratory syncytial virus (RSV) poses a widespread global burden that typically causes mild, cold-like symptoms in infected healthy adults. However, in vulnerable populations, such as the very young or older adults, RSV infection can lead to severe and potentially fatal disease. Both viral and host factors play a dynamic role in determining disease severity. In the host, dysregulation of both the innate and adaptive immune responses can result in unrestrained viral replication and excessive inflammation. Insight has been gained into the host factors that drive more severe disease following RSV infection using animal models and clinical studies. In this review, we discuss both clinical and in vivo animal model findings to elucidate host immune responses that contribute to disease severity, highlighting pathways that may serve as beneficial therapeutic targets. PubMed, ScienceDirect and Google Scholar were accessed to search for articles up to June 2026. Eligibility criteria included in vitro, in vivo, and clinical studies evaluating the factors associated with RSV disease severity, published in peer-reviewed journals.