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. 2020 Sep 7;5:192. doi: 10.1038/s41392-020-00308-2

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© The Author(s) 2020

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. 1 — High level of soluble checkpoints correlated with severe illness in COVID-19 patients. a Heatmap depicting the relative serum levels of soluble checkpoint molecules in asymptomatic (n = 5), mild/moderate (n = 60), and severe/critical (n = 44) patients with COVID-19. Each column of the heatmap shows a patient, while the rows represent different molecules. Color scale in the heatmap represents scores standardized across rows. b The lines of best fit showing temporal changes of soluble and membrane-bound checkpoints in six severe/critical patients during hospitalization. The 95% confidence interval (CI) indicated by colored areas. c Correlation heatmap of peripheral blood leukocyte subsets and soluble checkpoints concentrations (data are log-transformed) at baseline. Data shown are representative of 72 patients with complete data. The circle size is proportional to the correlation coefficient value. Blue circle: positive correlation; red circle: negative correlation; values with no significant correlation are marked with a black cross. d–g Receiver operating characteristic (ROC) analyses for soluble IDO (d), 4-1BB (e), TIM-3 (f), and CD27 (g) in COVID-19 patients (n = 104). h–k Kaplan–Meier survival plots stratified by serum levels of soluble IDO (h), 4-1BB (i), TIM-3 (j), and CD27 (k). The 44 severe/critical patients contributed a total of 33 ICU admissions. Among ICU survivors, the proportion of patients remaining in the ICU is shown according to their ICU stay time