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. 2022 Mar 11;3(3):204–215.e6. doi: 10.1016/j.medj.2022.01.009

Figure 2.

Figure 2

ddhC as the best-performing discriminator for viral infections in the discovery cohort

(A and B) Volcano plots showing median log2 fold change in intensity of each feature versus -log10p value in the discovery primary analysis cohort small molecule profiling dataset (n = 161) when comparing (A) viral cases (pre-COVID-19 viral and COVID-19) versus all other groups, and (B) viral versus bacterial (Gram-positive and Gram-negative bacteremia) cases, with controls omitted. Empirical threshold lines in red represent a fold-change of 16 (log2[fold-change] of 4) and p value of 0.01 (−log10[p value] of 2). Candidate biomarkers are shown in blue by mass:charge ratio/retention time, with 248.06/1.96 (ddhC) performing best. p-values generated using the two-sided Wilcoxon test and adjusted using the Benjamini-Hochberg procedure.

(C) AUCs for ddhC distinguishing viral versus all other and viral versus bacterial groups in the discovery primary analysis cohort. Blue. AUC of 0.954 (95% CI 0.923-0.986) for ddhC differentiating viral infections from all other groups (n = 161). Red. AUC of 0.944 (95% CI 0.905-0.983) for ddhC differentiating viral from bacterial infections, with controls omitted (n = 119).

(D and E) Relative ddhC intensity data in different patient groups in the discovery primary analysis cohort (n = 161). Points represent individual patients. Boxes represent IQRs with medians. (D) Viral versus all other groups. (E) Individual comparator groups. ∗2 samples in the COVID-19 group had a relative intensity of >700,000, not shown.

(F) Comparison of AUCs between ddhC, white cell count (WCC), lymphocyte count, and CRP as biomarkers to distinguish viral infections from all other groups in the discovery primary analysis cohort. Black - ddhC (AUC = 0.949 [95% CI 0.914-0.983], n = 148); green - WCC (AUC = 0.688 [95% CI 0.603-0.774], n = 148); red - lymphocyte count (AUC = 0.545 [95% CI 0.452-0.637], n = 148); blue - CRP (AUC = 0.585 [95 CI 0.483-0.687], n = 122). Healthy controls not included, as WCC, lymphocyte count, and CRP not available.