Dysregulation of lipid metabolism and pathological inflammation in patients with COVID-19

Abstract

In recent months, Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the world. COVID-19 patients show mild, moderate or severe symptoms with the latter ones requiring access to specialized intensive care. SARS-CoV-2 infections, pathogenesis and progression have not been clearly elucidated yet, thus forcing the development of many complementary approaches to identify candidate cellular pathways involved in disease progression. Host lipids play a critical role in the virus life, being the double-membrane vesicles a key factor in coronavirus replication. Moreover, lipid biogenesis pathways affect receptor-mediated virus entry at the endosomal cell surface and modulate virus propagation. In this study, targeted lipidomic analysis coupled with proinflammatory cytokines and alarmins measurement were carried out in serum of COVID-19 patients characterized by different severity degree. Serum IL-26, a cytokine involved in IL-17 pathway, TSLP and adiponectin were measured and correlated to lipid COVID-19 patient profiles. These results could be important for the classification of the COVID-19 disease and the identification of therapeutic targets.

Figure 1

Lipid profiles in COVID-19 patient serum. (A) Supervised partial least squares-discriminant analysis (PLS-DA) score plot and (B) discriminant lipidic features according to the variable importance on projection (VIP) score of mild, moderate and severe COVID-19 patients. The top 30 important lipids (VIP score ≥ 2.0 were summarized according to their VIP score value. The intensity of the colored boxes indicates the relative lipids abundance in each group (0 mild, 1 moderate and 2 severe patients). (C) Heatmaps of the auto-scaled mean lipid concentrations of each patient groups (0 mild, 1 moderate and 2 severe patients) of significantly altered lipids (p < 0.05) in six different lipid classes. The heatmap color code represents the relative lipid abundance. The concentrations of the metabolites were imputed, log(2) transformed, and Pareto scaled.

Figure 2

Targeted lipidomic analyses. Volcano plots of differential concentrations of 483 lipids in comparison of (A) severe patient serum to mild and (B) severe patient serum to moderate. The fold change of significant differentially abundant lipids (p < 0.05) in (C) severe condition versus mild and (D) severe condition versus moderate were plotted according to their significant p-value, reported in Tables 1 and 2, respectively.

Figure 3

TSLP protein levels in COVID-19 patient serum. (A) TSLP concentration expressed in pg/mL in the serum of COVID-19 patients at time of hospital admission (T0) or 1-week after admission (T1). (B) TSLP levels in severely affected individuals was significantly higher than in mild or moderate cases (adjusted p-value = 0.048 and 0.046 respectively).