Consensus Precision Medicine Framework for Sepsis Subtyping Builds on Hector Wong’s Legacy
Research By: Mihir Atreya, MD, MPH
Post Date: September 30, 2025 | Publish Date: Sept. 30, 2025
Results from SUBSPACE Consortium show promise at guiding care when critically ill patients need differing interventions
A team of scientists focused on improving outcomes for people with sepsis–a significant cause of death worldwide–has laid out a system for using genetic signatures to help emergency physicians rapidly determine key subtypes of sepsis and adjust interventions accordingly.
Details were published online Sept. 30, 2025, in Nature Medicine. The SUBSPACE Consortium work was led by Purvesh Khatri, PhD, a professor of biomedical informatics at Stanford University, and a large team of collaborators including experts from Cincinnati Children’s.
“This work, combined with the fact that we have an FDA-cleared clinical test, is an indicator that we are likely at the beginning of the era of precision medicine in critical care,” says Khatri, in a prepared announcement. “We finally have all the required tools to match the right people with the right treatment at the right time.”
View the full announcement from Stanford.
Sepsis occurs when the immune system overreacts to an infection, which can rapidly cascade into widespread inflammation and organ damage.
In 2024, sepsis affected an estimated 50 million people globally and caused 11 million deaths. Sepsis also is the leading cause of death for children under 5 years old.
However, treatments have remained limited primarily to antibiotics and organ support in critical care settings. Many clinical trials of treatments to modulate the immune system to control septic overreactions have failed.
The findings in Nature Medicine reflect a culmination of years of work to apply advances in medical technology to overcome complex challenges in sepsis treatment. The co-authors of the new research make special note of a long-time leadership role played by a pioneering expert in critical care medicine leader at Cincinnati Children’s.
“The authors would like to acknowledge Hector Wong for his outstanding achievements and lasting legacy in the field of transcriptomics and endotyping in sepsis,” the study states.
About Hector Wong, MD
Wong, a leader in critical care medicine research, practiced at Cincinnati Children’s for more than 25 years, where he long served as director of the Division of Critical Care Medicine and then as vice chair of the Department of Pediatrics at Cincinnati Children’s before his death in January 2022. He was 58.
Read more about Wong’s career at our Research Horizons science blog.
Among his many contributions, Wong and colleagues developed The Pediatric Sepsis Biomarker Risk Model (PERSEVERE), a first-of-its-kind tool that used biomarkers and clinical data for patient risk-stratification and gene-expression based endotyping to align therapies.
The biobank Wong launched at Cincinnati Children’s played an important role in the new SUBSPACE study.
The study includes Mihir Atreya, MD, MPH, Division of Critical Care Medicine as a co-author and thanks Kelli Harmon for her role in maintaining the Sepsis Genomics Biorepository at Cincinnati Children’s.
The SUBSPACE consortium builds on early endotyping studies by leveraging biospecimens from over 7,000 critically ill adults and children with sepsis. The team developed a Human Immune Dysregulation Evaluation Framework (HiDEF) that divides septic patients into four subtypes: balanced, myeloid dysregulation, lymphoid dysregulation, and system-wide dysregulation.
When re-organizing past clinical trial data according to these subtypes, new information emerged about the utility of several immune modulators, including corticosteroids and anakinra.
“For decades, sepsis has been considered the graveyard of immune therapies. Much like the word ‘cancer,’ the term ‘sepsis’ represents a catch-all syndrome,” Atreya says. “Significant variability in clinical characteristics, including age and host response, make it critical to identify disease subtypes to match the right treatment for the right patients. Moreover, the rapidity of disease progression and organ dysfunction pose tremendous challenges.”
The new research sets the stage for deploying rapid point-of-care tests.
“Application of such assays in real-time may lead to targeted, precision therapies and improved outcomes for critically ill patients, including children,” Atreya says.
About the biorepository
The biorepository at Cincinnati Children’s continues its work. It includes clinical data, genomic data and samples of blood, plasma, serum, and urine from critically ill children. It is available to any researcher at Cincinnati Children’s and to scientists from other institutions who collaborate with Cincinnati Children’s on research projects. Contact Basilia Zingarelli, MD, PhD, director of critical care basic science research, to learn more about the biorepository.
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| Original title: | A consensus immune dysregulation framework for sepsis and critical illnesses |
| Published in: | Nature Medicine |
| Publish date: | Sept. 30, 2025 |
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