| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T110 |
0-207 |
Sentence |
denotes |
To derive a plasma metabolite panel for distinguishing between COVID-19 patients and healthy controls, significant variables (p < 0.05) after adjustment of age, sex, and BMI were included in a starting pool. |
| T111 |
208-463 |
Sentence |
denotes |
In an iterative process, ten sets of variables were established from the starting pool (Figure 1 ), and one representative variable was finally selected from each set based on (1) smallest p value and (2) reported biological function from a PubMed search. |
| T112 |
464-658 |
Sentence |
denotes |
A final panel of ten metabolites was generated, which separated healthy controls from COVID-19 patients with AUC = 0.975 in a logistic regression model with leave-one-out (LOO) cross validation. |
| T113 |
659-899 |
Sentence |
denotes |
Among these metabolites, sphingosine-1-phosphate (S1P) was reduced (p < 0.001) in COVID-19, and its level was raised (p = 0.0065) at hospital discharge relative to admission in a small subset of patients followed longitudinally (Figure S2). |
| T114 |
900-1099 |
Sentence |
denotes |
S1P generation via sphingosine kinase-2 in monocyte-derived macrophages was recently shown to promote the resolution of inflammation by alveolar macrophages in acute lung injury (Joshi et al., 2020). |
| T115 |
1100-1286 |
Sentence |
denotes |
Biliverdin, the oxidized form of bilirubin, is part of the redox cycle constituting the primary physiologic function of bilirubin as a cytoprotective antioxidant (Baranano et al., 2002). |
| T116 |
1287-1514 |
Sentence |
denotes |
Increases in biliverdin (p = 0.0077) in COVID-19 probably indicated enhanced oxidative stress in disease state, and its level was reduced longitudinally at hospital discharge with marginal significance (p = 0.0558) (Figure S2). |
| T117 |
1515-1807 |
Sentence |
denotes |
Plasma 5-hydroxy-tryptophan was elevated in COVID-19 (p = 0.0203), and its depletion via induction of the indolamine 2, 3-dioxygenase pathway in human alveolar carcinoma type II-like cells was previously reported to suppress the growth of parainfluenza virus type 3 (Rabbani and Barik, 2017). |
| T118 |
1808-2164 |
Sentence |
denotes |
As for lipids, increases in lysophopholipids including lysophosphatidic acid (LPA) 18:1 (p = 0.0249) and lysophosphatidylcholine (LysoPC) 18:1 (p = 0.0350) were observed in COVID-19, while neutral lipids including medium-chain TAG 48:1(18:0) (p = 0.0190), long-chain TAG 60:3(18:1) (p = 0.0390), and DAG 34:1(16:1/18:0) (p = 0.0010) were generally reduced. |
| T119 |
2165-2302 |
Sentence |
denotes |
On the other hand, sphingolipids such as SM d18:1/18:1 (p = 0.002) and GM3 d18:1/25:0 (p = 0.0036) were generally increased with disease. |
| T120 |
2303-2383 |
Sentence |
denotes |
Figure 1 Plasma Panel for Differentiating COVID-19 Patients from Heathy Controls |
| T121 |
2384-2516 |
Sentence |
denotes |
Overview of selection scheme for plasma metabolite panel to differentiate COVID-19 (n = 50) patients from healthy controls (n = 26). |
| T122 |
2517-2777 |
Sentence |
denotes |
(A) From a total of 1,002 variables measured (598 lipids and 404 polar metabolites), variables with p < 0.05 between healthy controls and COVID-19 patients after adjustment for age, sex, and BMI were sieved out to form a starting pool comprising 322 variables. |
| T123 |
2778-2961 |
Sentence |
denotes |
(B) A starting variable with the lowest p value was selected, and variables with significant correlations (p < 0.05) to the starting variable selected were removed from consideration. |
| T124 |
2962-3192 |
Sentence |
denotes |
From remaining variables in the starting pool, the next starting variable with the second lowest p value was identified, and the process was repeated in an iterative fashion until all variables in the starting pool were exhausted. |
| T125 |
3193-3240 |
Sentence |
denotes |
This process generated a list of ten variables. |
| T126 |
3241-3379 |
Sentence |
denotes |
(C) Variables with significant correlations (p < 0.05) to each of the selected variables were added together to form ten established sets. |
| T127 |
3380-3552 |
Sentence |
denotes |
To select a representative variable from each established set, the variable with the smallest p value and with reported biological function from a Pubmed search was chosen. |
| T128 |
3553-3957 |
Sentence |
denotes |
A final panel of ten plasma metabolites, including S1P d18:1, SM d18:1/18:1, TAG60:3(18:1), LPA 18:1, biliverdin, TAG 48:1(18:0), DAG34:1(16:1/18:0), GM3 d18:1/25:0, lysoPC18:1, and 5-hydroxy-L-tryptophan, was generated, which distinguished between healthy controls and COVID-19 patients with an area under the curve (AUC) = 0.975 in a logistic regression model with leave-one-out (LOO) cross-validation. |
| T129 |
3958-4087 |
Sentence |
denotes |
Boxplots for the ten selected metabolites in the final panel were illustrated and p values were indicated on top of each boxplot. |
| T130 |
4088-4309 |
Sentence |
denotes |
Levels of polar metabolites measured using untargeted metabolomics were presented as corrected intensities, and lipids quantitated using targeted lipidomics were presented in nanomoles of lipids per liter (nmol/L) plasma. |
| T131 |
4310-4333 |
Sentence |
denotes |
See also Figures S2–S4. |
