Temporal Immune Profiling Reveals How Sepsis States Change Over Time

Sepsis is a life-threatening condition in which the immune response to infection becomes dysregulated, leading to rapid organ failure and death. Although antimicrobials and organ support remain standard care, many patients continue to deteriorate, and immune-targeted therapies have not reliably improved outcomes. A major challenge is that patients’ immune status can shift during critical illness, making it difficult to know when host-directed treatments are most likely to help. To address this timing gap, researchers have now mapped how immune states change over time in adult sepsis to inform the selection and timing of future therapies.

King’s College London has delineated three time-varying sepsis temporal immune states (STImS) that span the course from intensive care admission to recovery. The work, published in Immunity on August 28, 2026, builds a structured, time-based “immune profile” to capture the architecture of the host response during illness. The study proposes that aligning treatment strategies to these evolving immune states could improve how clinicians target the misfiring immune system.

Investigators analyzed blood from critically ill adults with sepsis treated at Guy’s and St Thomas’ NHS Foundation Trust, sampling at four points between admission and discharge from critical care. They assembled multiple layers of immune-response information from each sample, including immune cell data, gene expression, and changing protein expression. Using machine learning approaches, they integrated these layers to generate a comprehensive patient immune profile across time.

The resulting analyses revealed three distinct temporal immune states between admission and recovery, each marked by different immune-cell activities and response programs. Crucially, these immune states did not align with conventional clinical staging; for example, the “early” immune state (STImS1) was not the same as the early clinical stage often assigned on the day of diagnosis. The findings suggest that identifying a patient’s current immune state could help determine which immune-directed therapies to use and when to use them.

The study involved collaborators at University College London. The authors note that the next priority is to define what drives the transition from initial infection to sepsis, with the aim of identifying targets to reduce progression or severity.

“The main aim of this work was to build a profile of sepsis immune responses over time. When people are admitted to a hospital with sepsis, they are usually classed as having ‘early’ sepsis—but our findings show that this isn’t necessarily the case—their immune system may already be at later stages of the immune response. Knowing exactly what is happening to a patient’s immune system during sepsis could identify which treatments are likely to work best,” said Matthew Fish, former Ph.D. student at King’s College London and lead author of the paper.

“This research shows the importance of looking at the changing architecture of the immune system in sepsis over time, rather than just taking a snapshot view. We need to find better ways to treat the misfiring immune system. Only by understanding the intricacies of the immune system in all its component parts—by integrating and dynamically mapping cell and molecular immunobiology to determine why the very system designed to protect us from infections is misfiring in sepsis—can we begin to improve outcomes for patients by treating the misfiring immune system,” said Manu Shankar-Hari, professor of critical care medicine at King’s College London, honorary consultant at Guy’s and St Thomas’ NHS Foundation Trust and senior author of the paper.

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