Frailty as a framework to understand tuberculosis severity, recovery and sequelae

Tuberculosis (TB) causes profound systemic illness, and many survivors experience long-term sequelae associated with disability and premature mortality. Current TB severity indicators capture isolated aspects of disease and may not reflect the integrated physiological impact of infection on the host. Frailty, a multidimensional syndrome characterized by reduced physiological reserve and increased vulnerability to stressors, predicts adverse outcomes and guides clinical management in geriatrics. We propose frailty as an integrative framework for understanding the systemic effects of TB across the life course, encompassing disease severity, recovery, and long-term sequelae. We discuss biological mechanisms through which Mycobacterium tuberculosis infection may erode physiological reserve and promote frailty, including inflammation and metabolic and endocrine dysregulation. We further consider how frailty assessment could improve risk stratification and guide individualized supportive care to mitigate post-TB sequelae. Unlike aging-related frailty, TB-associated frailty may provide a unique opportunity to study mechanisms of resilience and recovery following severe infection.