We then evaluated if plasma lipids altered in COVID-19 were significantly correlated with relevant clinical indices. Spearman correlations were performed and only correlations with p < 0.05 were indicated as colored circles on the correlation plots (Figure 3 ). We observed that PCs, particularly PUFA-PCs and PCps, displayed significant negative correlations with clinical indices of systemic inflammation (IL-6, CRP, procalcitonin [PCT], ESR, and SF) (Figure 3A; Table S1). This suggested that reductions in plasma PUFA-PCs and PCps were associated with aggravated systemic inflammation. Corroborating these observations, it was shown in a small cohort of cystic fibrosis patients that serum PUFA-PCs were positive indicators of lung function (measured in terms of predicted forced expiratory volume in 1 s) and negative indicators of systemic inflammation (Grothe et al., 2015). In contrast to PCs, only PEps, but not PUFA-PEs, were significantly and negatively associated with clinical indicators of systemic inflammation (Figure 3B). PCps were also specifically and positively associated with apo-A1 (Figure 3A). Of outstanding interest, we observed that plasma GM3s represented the only pathologically altered lipid class that was strongly and negatively correlated with T cell count and CD4+ T cell count (Figure 3C), which progressively decreased as disease severity increased (Figure S1A). The negative correlations suggest that increases in plasma GM3s were associated with reductions in circulating CD4+ T cell counts in COVID-19. Reductions in circulating CD4+ T cells constitute an important feature of dysregulated immune response reported in COVID-19 (Qin et al., 2020).
Figure 3 Correlation of Plasma Lipids with Clinical Indices
Correlation plots illustrate spearman correlations between clinical indices with phosphatidylcholines (PC) (A), phosphatidylethanolamines (PE) (B), and multivesicular body-related lipids including bis(monoacylglyero)phosphate (BMPs), monosialodihexosyl gangliosides (GM3), and sphingomyelins (SMs) (C). Only correlations with p < 0.05 were indicated with colored circles. Negative correlations were shown in red and positive correlations were shown in blue, with sizes of circles representing the magnitude of the correlations. LeuC, leukocyte count; NC, neutrophil count; LC, lymphocyte count; PC_clinic, platelet count; Hb, hemoglobin; aPPT, activated partial thromboplastin time; PT, prothrombin time; D.dimer, D-dimer; ALB, albumin; ALAT, alanine aminotransferase; AST, aspartate aminotransferase; TBIL, total bilirubin; Serum Cr, serum creatinine; LDH, lactate dehydrogenase; IL.6, interleukin-6; CRP, C-reactive protein; PCT, procalcitonin; ESR, erythrocyte sedimentation rate; SF, serum ferritin; LA, lactic acid; TCellC, T cell count; CD4.TCellC, CD4+ T cell count; VLDL-Cho, very low-density lipoprotein cholesterol; HDLCho, high-density lipoprotein cholesterol; total cho, total cholesterol; TG, triglycerides; Fe, iron; ApoA1, apolipoprotein A1; ApoB, apolipoprotein B.