# Identification of sub-phenotypes of severely ill burn patients and risk for secondary sepsis: SEPSISBURN

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $454,313

## Abstract

Abstract
Severe burn injury rapidly activates a systemic inflammatory response and cardiovascular dysfunction, causing
distributive shock associated with increased endothelial permeability and organ injury. Sepsis is a leading
cause of death in patients with severe burn injury, accounting for nearly 75% of mortality among burn patients.
Preventing or recognizing sepsis early is key to preventing poor outcomes in burn patients. However, it is
difficult to (1) detect burn patients at higher risk of sepsis at the time of intensive care unit presentation and (2)
distinguish between sepsis and the non-infective inflammatory response to severe burn injury. To date, most
data for detecting infection and sepsis in non-burn patients do not necessarily inform diagnosis in the burn
patient population given the specificities of burn injury. Though some studies have identified potential
biomarkers as candidate septic markers in burn patients, these markers are derived from a very small number
of patients or were not combined and showed limited predictive value. Thus, due to the unique
pathophysiology of severe burns, there is an unmet clinical need to identify early biomarker signatures of
patients at risk of sepsis and septic shock in the burn patient population.
Our central hypothesis is that the initial host response to burn injury could predispose to secondary sepsis.
That is, a dysregulated cardiovascular injury and inflammatory profile in adult patients with severe burn injury
exposes burn patients to a higher risk of developing sepsis. In this proposal, we will longitudinally analyze
plasma samples and clinical outcomes in a large cohort of burn patients (n=400) with severe burn injury.
Biomarker analysis of immune dysregulation and cardiovascular injury will be used to define sub-phenotypes of
patients and linked to the primary endpoint (sepsis) and secondary outcomes (mortality, ICU length of stay,
organ failure). Proof of principle results from this large prospective cohort study will then be used to guide and
inform future prospective trials and emulated trials of therapeutic interventions to identify (1) populations at
higher risk of sepsis and (2) therapeutic pathways that could be targeted to prevent secondary sepsis in this
high-risk population. Finally, we will compare proteomic signatures between burn patients without sepsis (i.e.,
non-septic systemic inflammatory response) and burn patients with sepsis and control non-burn critically ill
patients with sepsis or septic shock. The results of these studies will provide key insights into the identification
of biomarkers and proteomic signatures specific to sepsis and improve our ability to recognize sepsis.

## Key facts

- **NIH application ID:** 10927455
- **Project number:** 5R01GM151494-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Matthieu Legrand
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $454,313
- **Award type:** 5
- **Project period:** 2023-09-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10927455

## Citation

> US National Institutes of Health, RePORTER application 10927455, Identification of sub-phenotypes of severely ill burn patients and risk for secondary sepsis: SEPSISBURN (5R01GM151494-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10927455. Licensed CC0.

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