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. 2021 Jul 6;28(12):3297–3315. doi: 10.1038/s41418-021-00817-9

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — A Volcano plot identifying statistically different serum metabolites between patients experiencing short-term viral RNA shedding (SVS) and those experiencing long-term viral RNA shedding (LVS) in Cancer_FR1_TR cohort. Metabolites significantly different between both groups are in red and annotated (P < 0.05, FC > 0.5). B Levels of murideoxycholic acid according to the duration of viral shedding in Cancer_FR1_TR (left panel) and Spearman correlation with absolute lymphocyte count (ALC) (right panel). The color code corresponds to the category of cycle threshold (Ct) and ALC at diagnosis. C, D Serum concentrations of deoxycholic acid according to the duration of viral shedding in Cancer_FR1_TR (C) and the severity of COVID-19 infection in cancer-free individuals (D). E Waterfall plot of Spearman’s correlation coefficient (r_s) between ALC and 221 metabolites in the serum of patients diagnosed positive for COVID-19. F N1, N8 diacetylspermidine relative abundance in controls, SVS and LVS patients in the Cancer_FR1 cohort, that is negatively correlated with the ALC. The color code corresponds to the category of cycle threshold (Ct) and ALC at diagnosis. G Levels of N1, N8 diacetylspermidine in noncancer COVID-19 patients according to the clinical severity compared to COVID-19-negative controls (Ctls) (P < 0.0001) (G, left panel), that are negatively correlated with the absolute lymphocyte count (ALC) (G, right panel). Box plots display a group of numerical data through their 3rd and 1st quartiles (box), mean (central band), minimum and maximum (whiskers). Each dot represents one sample, each patient being drawn once for cancer-free individuals and one to two times for cancer patients. Statistical analyses used one-way ANOVA with Kenward–Roger method to take into account the number of specimen/patient (B, left panel, C–E, left panel): *P < 0.05, **P < 0.01), non-parametric unpaired Wilcoxon test (Mann–Whitney) for each two-group comparison: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.