Figure 3.
Disruption of specialized proresolving mediator (SPM) pathways with increased disease severity in patients with coronavirus disease 2019 (COVID-19). Peripheral blood was collected from patients with COVID-19 with mild (WHO scale 3–4; WHO 3–4) or severe disease (WHO scale 5; WHO 5). A–C, Plasma lipid mediators were identified and quantified using liquid chromatography tandem mass spectrometry based lipid mediator profiling, and partial least squares discriminant analysis (PLS-DA) was performed on identified mediators for the indicated patient sub-groups. Top: Scores plot with 95% CI. Bottom: Variable Importance in Projection scores plot. For (A), n=25 WHO 3–4 patients and n=13 WHO 5 patients; for (B), n=21 WHO 3–4 improving/stable patients and n=4 WHO 3–4 deteriorating/death patients; for (C), n=6 WHO 5 improving/stable patients and n=7 WHO 5 deteriorating/death patients. D–K, Whole blood from patients with COVID-19 was incubated with lineage-marker antibodies for neutrophils and monocyte subsets in combination with antibodies against (D–G) lipid mediator biosynthetic enzymes or (H–K) SPM receptors and their expression was evaluated using flow cytometry. For (D–G), n=14 WHO 3–4 patients (for COX-2, ALOX15), n=8 WHO 3–4 patients (for ALOX5 [5-lipoxygenase], ALOX12, ALOX15B), n=6 WHO 5 patients (for COX-2, ALOX15), n=6 WHO 5 patients (for ALOX5, ALOX12, ALOX15B). For (H–K), n=7 WHO 3–4 patients and n=4 WHO 5 patients (except for GPR37 where n=3 WHO 5 patients). Statistical differences between WHO 3–4 and WHO 5 patients with COVID-19 were established using Mann-Whitney test for each parameter and raw P values are displayed.