How does older people’s immune system place them at high risk of sepsis and death?

Increased risk of sepsis and death from infectious causes among the elderly is a well-known phenomenon—particularly as witnessed in the Covid-19 era— and is in part due to 2 major age-related alterations of their immune system: 1. Defective T and B cell functions in response to acute infections; and 2. Once infection sets in, inadequate control of sepsis-induced pro-inflammatory response and its attendant procoagulant state. Interestingly, the essential elements of the innate immunity (eg, neutrophils, dendritic cells, complements) are generally spared from the effects of aging.1,2

Increased susceptibility of the elderly to acute infections is in part caused by poorer T helper cell function and suboptimal B cell humoral response to neoantigens. Despite this, serum levels of pro-inflammatory cytokines such as IL-1, IL-6,TNF-alpha, and IFN-gamma are intact.  In fact, production of IL-6 and its duration of response is actually increased in the elderly.1,2

Poor control of the inflammatory state due to sepsis in older patients may be related to the difficulty in clearing a pathogen or dysfunction in the signaling by counter-regulatory cytokines, such as IL-10.2 Either way, unchecked inflammatory response is deleterious to the patient and is associated with increased risk of thrombosis and thromboembolism, multiorgan system failure, septic shock and death. 

Bonus Pearl: Did you know that even in the absence of infection, older people are more prone to thrombosis and thromboembolism , in part related to elevated plasma levels of fibrinogen, as well as factor VII, VIII, and IX, among others?2,3  

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  1. Ticinesi A, Lauretani F, Nouvenne A, et al. C-reactive protein (CRP) measurement in geriatric patients hospitalized for acute infection. Eur J Intern Med 2017;37:7-12.
  2. Opal SM, Girard TD, Ely EW. The immunopathogenesis of sepsis in elderly patients. Clin Infect Dis 2005;41: (Suppl 7) S504-12.
  3. Mari D, Coppola R, Provenzano R. Hemostasis factors and aging. Experimental Gerontology 2008;43:66-73.

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!


How does older people’s immune system place them at high risk of sepsis and death?

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