The Plasma Lipidomic Landscape in Patients with Sepsis due to Community-acquired Pneumonia

Rationale: The plasma lipidome has the potential to reflect many facets of the host status during severe infection. Previous work is limited to specific lipid groups, or focused on lipids as prognosticators. Objectives: To map the plasma lipidome during sepsis due to community-acquired pneumonia (CAP), and determine disease-specificity and associations with clinical features. Methods: We analyzed 1833 lipid species, across 33 classes, in 169 patients admitted to the intensive care unit (ICU) with sepsis due to CAP, 51 non-infected ICU patients and 48 outpatient controls. In a paired analysis we reanalyzed patients still in the ICU four days after admission (n=82). Measurements and Main Results: 58% of plasma lipids were significantly lower in CAP-sepsis patients compared to outpatient controls (6% higher, 36% not different). We found strong, lipid class-specific associations with disease severity, validated across two external cohorts, and inflammatory biomarkers, in which triacylglycerols, cholesterol esters, and lysophospholipids exhibited the strongest associations. 36% of lipids increased over time, stratification by survival revealed diverging lipid recovery, which was confirmed in an external cohort; specifically, a 10% increase in cholesterol ester levels was related to a lower odds ratio (OR 0.84, p=0.006) for 30-day mortality (absolute mortality: 18/82). Comparison with non-infected ICU patients delineated a substantial common illness response (57.5%), and a lipidomic signal distinct for patients with CAP-sepsis (37%). Conclusions: Patients with sepsis due to CAP display a time-dependent and partially disease-specific shift in their plasma lipidome that correlates with disease severity and systemic inflammation, and is associated with higher mortality.