Immune Biomarkers Could Identify Risk of Chronic Critical Illness on ICU Admission

A subset of patients develop chronic critical illness, defined as dependence on intensive care beyond 14 days, though the drivers of this trajectory have remained unclear. Early recognition of patients likely to follow this course could help clinicians adjust care pathways. New findings now demonstrate an immune biomarker profile that distinguishes these patients soon after injury.

A new study published in The Journal of Immunology identifies biomarkers of a distinct T helper 17 (Th17)-biased immunophenotype that could help flag risk for chronic critical illness at intensive care unit admission. The profile includes increased neutrophils, elevated Th17 cells, and amplified inflammatory cytokines, including interferon-gamma (IFN) and interleukin-17A (IL-17A). Together, these markers point to a misdirected or imbalanced immune response compared with trauma patients who recovered within 14 days.

Researchers collected blood samples from patients with blunt or penetrating trauma on intensive care unit days 4, 7, 10, 14, and 28, or until discharge. Patients were stratified by recovery trajectory: rapid recovery within 7 days, intermediate recovery between 7 and 14 days, and chronic critical illness beyond 14 days. The comparisons were designed to uncover immunologic differences that explain why only some patients progress to prolonged critical illness.

IL-17A emerged as the most informative discriminator of chronic critical illness compared with rapid or intermediate recovery, with some chronic critical illness patients showing elevated IL-17A as early as day 1 in the intensive care unit. The article was published in The Journal of Immunology on June 25, 2026. Collaborating institutions included the University of Washington and the University of Minnesota. According to the summary, identifying patients at increased risk could enable earlier intervention, potentially shortening intensive care stays and improving outcomes. The team plans to further delineate the immune mechanisms driving chronic critical illness.

“Our findings are highly novel, challenging what scientists have long thought about the immune changes that cause organ dysfunction and mortality in severely injured trauma patients. Rather than the immune system being exhausted, our data show overactivity and dysfunction,” said Dr. Scott Brakenridge, Professor of Surgery at the University of Washington and senior author for the study.

“As the immune changes observed in CCI patients are distinct from patients who recover before 14 days, these findings reveal immunological features that may be used to quickly identify trauma patients at risk for CCI when they are admitted to the ICU. Developing a test for this profile would allow clinicians to tailor patient care, quickening recovery time and saving lives,” said Caleb Kim, PhD candidate at the University of Minnesota and first author of the paper.