Fig. 1. Long-term trajectory of sepsis and SAE.

a | Long-term sequelae of sepsis. Sepsis causes excessive inflammation (often referred to as a ‘cytokine storm’), and subsequent chronic alterations in the peripheral immune system²¹. Compared with healthy individuals, patients with sepsis show both features of enhanced inflammation and enhanced immunosuppression. For example, there is expansion of myeloid-derived suppressor cell populations and higher plasma levels of C-reactive protein (CRP), IL-6 and IL-8 in patients with sepsis^5,21. Immunoparalysis is linked to low lymphocyte counts and increased levels of immunosuppressive proteins in plasma with an elevated risk of infections^22,23. b | Proposed model of dynamic changes seen in cognitive functions following onset of sepsis. Around half of the patients present with delirium and coma in the intensive care unit (ICU)^8,11, but whereas some survivors show restoration of cognitive functions during the recovery phase, others show persistence of cognitive impairments for 2 years or more after sepsis onset^11,26–28. CNS, central nervous system; SAE, sepsis-associated encephalopathy.