Age-Related Susceptibility and Severity

Age is one of the strongest and most consistent determinants of infectious-disease risk. Both the very young and the old are more likely to become infected, to develop severe disease, and to die, producing the familiar U- or J-shaped age curves of infection mortality. This topic explains why the immature immune system of infancy and the ageing immune system of later life shift susceptibility and severity, and how those shifts appear in population data.

Definition

Age-related susceptibility and severity refers to the systematic variation in the probability of acquiring infection and in the resulting disease severity across the lifespan, driven by the developing immune system in early life and by age-associated immune decline (immunosenescence) in later life.

Scope

The topic covers age as a host determinant of who becomes infected and how severely, spanning the immature immunity of early life and the immunosenescence of older age. It treats age effects at population and mechanistic-overview level, not as clinical management or age-specific dosing. It connects to immunocompromise and to comorbidity, which often accumulate with age, but focuses specifically on chronological age and immune maturation as drivers of variation.

Core questions

• Why are infants and older adults more susceptible to infection and to severe disease?
• How do immune maturation and immunosenescence change the response to pathogens?
• What do age-specific patterns of incidence and case-fatality look like at the population level?
• How does age interact with comorbidity and immunocompromise to shape risk?

Key concepts

• Immunosenescence
• Immune maturation in early life
• Extremes of age
• Age-specific case-fatality
• Inflammaging
• U-shaped age-mortality curve

Key theories

Immunosenescence and age-dependent innate immune dysregulation

Shaw and colleagues describe how innate immunity becomes dysregulated with age, with altered signalling and inflammatory responses that impair pathogen control and contribute to greater susceptibility and severity in older adults.

Mechanisms

In early life the adaptive immune system is still developing and immunological memory is limited, so infants depend heavily on innate defences and maternally derived antibody and are vulnerable to pathogens they have not yet encountered. In later life, immunosenescence reshapes both arms of immunity: Shaw and colleagues document age-dependent dysregulation of innate immunity, with blunted and dysregulated responses that impair pathogen clearance even as low-grade inflammation rises. The net result at both extremes is reduced capacity to limit infection and damage, which manifests as higher susceptibility and higher severity for many pathogens.

Clinical relevance

Age is routinely used to describe infection risk in populations and to identify groups in whom severe outcomes concentrate, such as young infants and older adults. This topic is a reference for understanding why age structures infectious-disease burden; it characterises population patterns and mechanisms and does not provide individual diagnostic or treatment recommendations.

Epidemiology

Age gradients in infection are striking. The risk of dying from coronavirus disease 2019 rose steeply with age in the model-based estimates of Verity and colleagues, illustrating a pronounced old-age severity gradient for a single pathogen. At the other extreme, O'Brien and colleagues estimated that Streptococcus pneumoniae caused a very large share of severe disease and death in children younger than five years, underscoring the burden concentrated in early life. Together these show how a single age axis can dominate the population distribution of infectious-disease severity.

Key figures

• Albert Shaw
• Ruth Montgomery
• Daniel Goldstein

Seminal works

• shaw-2013
• verity-2020
• obrien-2009

Frequently asked questions

Why are infants and older adults most at risk from infections?

Infants have an immature, still-developing immune system with limited memory, while older adults experience immunosenescence, an age-related decline and dysregulation of immune function. Both reduce the ability to control pathogens, raising susceptibility and severity at the extremes of age.

Does age affect who gets infected, how severe the disease is, or both?

Both. Age influences the probability of acquiring infection and, often more strongly, the probability of severe disease and death, as seen in the steep rise in coronavirus disease 2019 mortality with age.