Endotype Transitions During the Acute Phase of Pediatric Septic Shock Reflect Changing Risk and Treatment Response

Area of Science:

• Pediatric critical care medicine
• Immunology
• Genetics

Background:

• Septic shock endotypes A and B were previously identified based on 100 genes.
• These endotypes are associated with differing outcomes and corticosteroid responsiveness.

Purpose of the Study:

• To determine if septic shock endotypes change during the initial three days of illness in children.
• To investigate the association between endotype changes, corticosteroid response, and patient outcomes.

Main Methods:

• An observational cohort study involving 375 children with septic shock.
• Measurement of 100 endotyping genes at day 1 and day 3 of illness.
• Multivariable logistic regression analysis adjusted for illness severity, age, and comorbidity.

Main Results:

• A significant proportion of children transitioned between endotypes A and B from day 1 to day 3 (42% from A to B, 32% from B to A).
• Endotype A at day 1 was linked to increased mortality risk, modified by day 3 endotype.
• Corticosteroids increased mortality risk for patients who remained endotype A.

Conclusions:

• Septic shock endotypes are dynamic during the acute illness phase in children.
• Endotype shifts influence patient outcomes and corticosteroid efficacy.
• Persistent endotype A is associated with the highest risk of adverse outcomes.