# Omega-3 fatty acids as host-directed immunomodulatory therapeutics in sepsis: real-world evidence supporting drug development potential for systemic inflammatory diseases

## TL;DR

This study shows that omega-3 fatty acids may reduce ICU mortality in sepsis patients by modulating the immune response, suggesting potential for treating inflammatory diseases.

## Contribution

The study provides real-world evidence supporting the use of omega-3 fatty acids as host-directed immunomodulatory therapeutics in sepsis.

## Key findings

- Omega-3 FA supplementation was associated with significantly reduced adjusted ICU mortality in sepsis patients.
- Advanced age, elevated CRP, and higher NE dependence negatively modulated omega-3 FA efficacy.
- Kaplan–Meier analysis confirmed improved survival in the omega-3 FA group.

## Abstract

Sepsis remains a leading cause of intensive care unit (ICU) mortality worldwide, characterized by dysregulated inflammation and immune dysfunction mechanisms also central to many neglected tropical diseases. Omega-3 fatty acids (Ω-3 FAs) possess potent anti-inflammatory and immunomodulatory properties that may improve survival outcomes in such conditions. This retrospective real-world study evaluated the impact of Ω-3 FA supplementation on ICU mortality among patients with sepsis and identified prognostic factors influencing therapeutic efficacy.

Patients admitted with sepsis to the ICU of Shenzhen People’s Hospital between December 2016 and July 2019 were retrospectively analyzed. Propensity score matching (PSM) was applied at a 1:2 ratio between Ω-3 FA-treated and control groups using covariates including age, sex, diagnosis, norepinephrine (NE) requirement, hemofiltration (HF), C-reactive protein (CRP), and lymphocyte count. Logistic regression and inverse probability of treatment weighting (IPTW) were performed to determine the independent effect of Ω-3 FAs on mortality.

A total of 633 patients were included (Ω-3 FA group, n = 211; control, n = 422). The unadjusted mortality rate was 32.7% in the Ω-3 FA group and 24.6% in controls (p = 0.032). Univariate analysis showed a weak protective effect of Ω-3 FAs (HR = 0.74, 95% CI: 0.54–1.02, p = 0.062). After adjusting for age, HF and NE requirements, CRP, lymphocyte count, Sequential Organ Failure Assessment (SOFA) score, and abdominal infection, Ω-3 FAs demonstrated a significant protective effect (HR = 0.60, 95% CI: 0.43–0.83, p = 0.003). Kaplan–Meier analysis confirmed improved survival in the Ω-3 FA group (p = 0.038). Advanced age, elevated CRP, and higher NE dependence were identified as factors that negatively modulated Ω-3 FA efficacy.

Omega-3 fatty acid supplementation was associated with significantly reduced adjusted ICU mortality in sepsis, underscoring its host-directed immunomodulatory properties. These findings highlight the translational potential of Ω-3 FAs as adjunct therapeutic agents in sepsis and other infection-associated inflammatory disorders, supporting further drug development toward host-directed treatments for neglected tropical diseases.