**Abstract**

Respiratory syncytial virus (RSV) is not only a major cause of severe lower respiratory tract infection (LRTI) in infancy but is increasingly recognised as an important pathogen in later life. RSV infection is associated with a wide spectrum of disease ranging from asymptomatic infection to life-threatening bronchiolitis and pneumonia. Research has demonstrated that there exists a complex interplay between viral and host factors that determines the severity of disease following RSV infection. Several factors determine RSV virulence including the infective properties of individual strains and viral load (VL). Disease outcome from RSV infection is also impacted considerably by a variety of host factors with the host immune response increasingly recognised as pivotal. This chapter outlines our current understanding of these factors and provides an oversight of their relative importance.

**Keywords:** respiratory syncytial virus, disease severity, viral load, immunology, genotype

### **1. Introduction**

Respiratory syncytial virus (RSV) has long been recognised as a cause of severe lower respiratory tract infection (LRTI) in early childhood with increasing evidence of its role as an important pathogen in later life [1]. RSV has many intriguing features including its worldwide distribution, its capacity to cause severe disease in early childhood and its extended impact on respiratory health [2]. Consequently, RSV has been the focus of comprehensive study including host and viral determinants of disease severity.

Serologic data has demonstrated that a high proportion of children (between 50 and 70%) will be infected with RSV in the first year of life [3, 4]. Asymptomatic infection is infrequent during infancy with most infants developing clinical features of an upper respiratory tract infection alone [5]. Following an initial prodromal URTI phase, 25–40% of those infected will progress to develop signs and symptoms of bronchiolitis with tachypnoea and chest recession [5]. Bronchiolitis is usually a mild illness in most infants, but a small proportion (2–3%) will develop severe bronchiolitis necessitating hospitalisation [6]. It has been estimated that nearly 33.8 million new cases of RSV-associated LRTI occur worldwide in children

under 5 years of age leading to approximately 3.4 million hospitalizations annually [7]. Mortality from RSV infection in developed countries is rare during infancy although there are an estimated 66,000 and 239,000 yearly deaths in children younger than 5 in the developing world [7, 8].

The major clinical manifestation of RSV in older children and adults is upper respiratory tract illness (rhinitis and acute otitis media) although symptoms tend to last longer and there is an increased incidence of cough and wheeze compared to other respiratory viral infections [9, 10]. Immunity following RSV infection is only effective for a matter of months before the individual is once again susceptible to reinfection [11]. Consequently, reinfection occurs throughout life. LRTI is unusual although RSV accounts for a significant percentage (>4%) of community-acquired pneumonias during epidemics [12]. Elderly adults have an increased risk of lower respiratory tract involvement, with 30–40% of patients having auscultatory findings on examination of the chest [13].

RSV is evidently associated with a wide spectrum of disease which has led to significant interest into those factors that determine the nature of the clinical response to infection. Host, viral and geographical factors interact to dictate the clinical outcome of any viral infection. The viral and host factors that influence the human response to RSV infection are the focus of this chapter.
