Figure 4 Differential Correlation Analyses of Plasma Lipids in Mild COVID-19 Relative to Healthy Controls
Multiscale embedded correlation network analysis illustrates the differential correlation of lipids in mild COVID-19 relative to healthy controls to reveal changes in lipid metabolic pathways upon early stage of viral infection. Only lipid pairs with significant differential correlations (empirical p < 0.05) were included. Sign/sign indicates direction and strength of correlation in control/mild COVID-19, and number that follows indicates number of lipid pairs in the global networks exhibiting this pattern of change. For instance, red line +/++ 1 in the upper legend of the global networks indicates that correlation between two connected lipid pairs was positive (+) in controls, and the correlation became even more strongly positive (++) in mild COVID-19 patients, as defined by statistically significant (p < 0.05) increase in correlation coefficients between the lipid pair across the two conditions. A total of 1 lipid pair connected by red lines in the global network displayed this pattern of change (+/++). Blue line +/− : positive in controls → negative in mild COVID-19. Teal line +/0: positive in controls → insignificant in mild COVID-19. Gold line ++/+: strongly positive in controls → weaker positive in mild COVID-19. Purple line 0/−: insignificant correlation in controls → negative correlation in mild COVID-19. Gray line 0/+: insignificant correlation in controls → positive correlation in mild COVID-19. Four modules (I–IV) of biological interest were circled and expanded for better visual clarity. (I) Module with hub PS 34:1 connected to numerous PEs by teal lines, indicating PS-PE positive correlations in healthy controls were lost in mild COVID-19. (II) Module with hub BMP 38:5(18:1/20:4) connected to CEs by blue lines, indicating BMP-CE correlations became negative in mild COVID-19. (III) Module with GM3 d18:0/25:0 as hub connected to several PSs by blue and purple lines, indicating GM3-PS correlations became negative in mild COVID-19. (IV) Module with LysoPC 16:1 as the hub connected to numerous PUFA-PEs by blue lines, indicating lysoPC-PUFA-PE correlations changed from positive in healthy controls to negative in mild COVID-19. PS, phosphatidylserines; PE, phosphatidylethanolamines; BMP, bis(monoacylglycero)phosphates; CE, cholesteryl esters; GM3, monosiaolodihexosyl gangliosides; PUFA-PE, polyunsaturated PEs.