Biomarkers of respiratory syncytial virus (RSV) infection: specific neutrophil and cytokine levels provide increased accuracy in predicting disease severity

Abstract

Despite fundamental advances in the research on respiratory syncytial virus (RSV) since its initial identification almost 60 years ago, recurring failures in developing vaccines and pharmacologic strategies effective in controlling the infection have allowed RSV to become a leading cause of global infant morbidity and mortality. Indeed, the burden of this infection on families and health care organizations worldwide continues to escalate and its financial costs are growing. Furthermore, strong epidemiologic evidence indicates that early-life lower respiratory tract infections caused by RSV lead to the development of recurrent wheezing and childhood asthma. While some progress has been made in the identification of reliable biomarkers for RSV bronchiolitis, a "one size fits all" biomarker capable of accurately and consistently predicting disease severity and post-acute outcomes has yet to be discovered. Therefore, it is of great importance on a global scale to identify useful biomarkers for this infection that will allow pediatricians to cost-effectively predict the clinical course of the disease, as well as monitor the efficacy of new therapeutic strategies.

Keywords: Asthma; Brain-derived growth factor (BDNF); Bronchiolitis; Lung development; Nerve growth factor (NGF).

Figure 1. Neurotrophins as biomarkers of RSV bronchiolitis

Patients with acute RSV bronchiolitis have significantly higher concentrations of NGF and BDNF proteins in the cellular fractions sampled from their airways compared to non-infected infants or infants with acute bronchiolitis caused by adenoviral or parainfluenza infections whose airways express minimal baseline levels of both neurotrophins. Furthermore, epithelial cells and macrophages from the airways of RSV-infected infants have strong surface expression of the high-affinity NGF receptor TrkA, whereas in the absence of RSV infection this receptor is virtually absent.

Figure 2. Blood NGF in RSV bronchiolitis

Bar graph shows NGF concentrations in the blood drawn at 72 hours post-intubation from 6 infants with RSV-positive LRTI and 6 RSV-negative post-surgical infants without LRTI. Blood samples drawn from the same patients at earlier time points showed no statistical significance. *P < 0.05.