Lipidomic and metabolomic changes in community-acquired and COVID-19 pneumonia

Abstract

This prospective observational study compared the 1H NMR blood lipidomes and metabolomes of 71 patients with community-acquired pneumonia (CAP), 75 patients with COVID-19 pneumonia, and 75 healthy controls (matched by age and sex) to identify potential biomarkers and pathways associated with respiratory infections. Both pneumonia groups had comparable severity indices, including mortality, invasive mechanical ventilation, and intensive care unit admission rates. Patients with COVID-19 pneumonia exhibited more pronounced hypolipidemia, with significantly lower levels of total cholesterol and LDL-c compared to patients with CAP. Atherogenic lipoprotein subclasses (VLDL-cholesterol, IDL-cholesterol, IDL-triglyceride, and LDL-triglyceride/LDL-cholesterol) were significantly increased in severe cases of both pneumonia types, while lower HDL-c and small, dense HDL particles were associated with more severe illness. Both infected groups showed decreased esterified cholesterol and increased triglycerides, along with reduced phosphatidylcholine, lysophosphatidylcholine, PUFA, omega-3 fatty acids, and DHA. Additionally, infected patients had elevated levels of glucose, lactate, 3-hydroxybutyrate, and acetone, which are linked to inflammation, hypoxemia, and sepsis. Increased levels of branched-chain amino acids, alanine, glycine, and creatine, which are involved in energy metabolism and protein catabolism, were also observed. Neurotransmitter synthesis metabolites like histidine and glutamate were higher in infected patients, especially those with COVID-19. Notably, severe infections showed a significant decrease in glutamine, essential for lymphocyte and macrophage energy. The severity of COVID-19 pneumonia was also associated with elevated glycoprotein levels (glycoprotein A, glycoprotein B, and glycoprotein F), indicating an inflammatory state. These findings suggest that metabolomic and lipidomic changes in pneumonia are connected to bioenergetic pathways regulating the immune response.

Keywords: COVID-19; HDL; NMR; lipidomics; metabolomics; pneumonia.

Fig. 1

Lipoprotein subclasses for the control, COVID pneumonia and CAP based on clinical severity. The data presented in the figures represent medians with quartiles. Statistical analysis was performed using T-tests to compare disease severity (light grey) and pneumonia etiology (dark grey), ANOVA to assess group differences (black), and two-way ANOVA to analyze the interaction between pneumonia type and disease severity. Significance levels are denoted as follows: ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001.

Fig. 2

Lipid components differentiated by pneumonia severity. The data presented in the figures represent medians with quartiles. Statistical analysis was performed using T-tests to compare disease severity (light grey) and pneumonia etiology (dark grey), ANOVA to assess group differences (black), and two-way ANOVA to analyze the interaction between pneumonia type and disease severity. Significance levels are denoted as follows: ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001.

Fig. 3

Low-molecular-weight metabolite profile. The data presented in the figures represent medians with quartiles. Statistical analysis was performed using T-tests to compare disease severity (light grey), pneumonia etiology (dark grey), ANOVA to assess group differences (black), and two-way ANOVA to analyze the interaction between pneumonia type and disease severity. Significance levels are denoted as follows: ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001.

Fig. 4

Glycoproteins. The data presented in the figures represent medians with quartiles. Statistical analysis was performed using T-tests to compare disease severity (light grey), pneumonia etiology (dark grey), ANOVA to assess group differences (black), and two-way ANOVA to analyze the interaction between pneumonia type and disease severity. Significance levels are denoted as follows: ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001.

Fig. 5

Bivariate correlations between glycoproteins and lipoprotein profiles, lipid metabolites, and LMWM.

Fig. 6

Multivariant analysis. Partial least squares discriminant analysis (PLS-DA) and ROC curve analysis performed: CAP/COVID-19 pneumonia and moderate/severe.