For decades, progress in developing new treatments for critical illnesses such as sepsis, acute respiratory distress syndrome (ARDS), and trauma has been stalled by one fundamental challenge: although these conditions are treated as single diseases, every patient’s body responds differently. This heterogeneity has been a major barrier to advancing care.
Two new studies now confront this problem directly, offering a unified, data-driven way to classify patients into distinct biological subtypes.
The first study, “A consensus blood transcriptomic framework for sepsis,” analysed data from more than 1,800 sepsis patients. Using blood transcriptomics, a technique that measures the activity of thousands of genes to capture a real-time snapshot of immune function, the researchers created a harmonised classification system that identifies three Consensus Transcriptomic Subtypes (CTSs) of sepsis, each defined by a unique molecular profile:
- CTS1: A strong, classic inflammatory response driven by an aggressive yet immature neutrophil reaction.
- CTS2: Marked by abnormalities in blood clotting and haem metabolism, a key component of red blood cells.
- CTS3: Characterised by antiviral interferon activity and immune features typically seen in organ transplant rejection.
The goal was to establish a standardised model for sepsis research,. Study researchers unified years of data into one robust molecular framework.
The findings also carry an important warning. A reanalysis of a major clinical trial revealed that patients with the CTS2 subtype were harmed by corticosteroids. This underscores the urgent need to abandon the one-size-fits-all approach to treatment.
The second paper, “A consensus immune dysregulation framework for sepsis and critical illnesses,” from the international SUBSPACE consortium expands on this work. Drawing on over 7,000 patient samples from 37 cohorts, the team identified two core patterns of immune dysregulation: one in myeloid cells and one in lymphoid cells. These same patterns appeared not only in sepsis but also in ARDS, trauma, and burns, revealing shared biological mechanisms across multiple critical illnesses.
Together, these complementary studies provide a powerful new framework for understanding the biology of critical illness. They pave the way for clinical trials designed around molecular subtypes, bringing the promise of precision medicine within reach for the most vulnerable patients.
Source: University of Malta
Image Credit: iStock
