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. 2021 May 25;13:118. doi: 10.1186/s13148-021-01102-9

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© The Author(s) 2021

Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 6 — DNA methylation is associated with COVID-19 outcomes. A Volcano plot shows genes associated with dichotomized GRAM-risk scores, either hyper-methylated (red) or hypo-methylated (blue). B DNA methylation levels at 77 differentially methylated positions (DMPs) correlate with disease severity in COVID-19 patients. DMRs (N = 19) associated with the GRAM-score were identified in COVID-19 patients (N = 100). DMRs were ascertained as regions with at least 3 consecutive CpGs where > 75% of the CpGs in the region had a FDR p value < 0.05 and all were either hyper-methylated or hypo-methylated. DNA methylation levels of the DMPs (N = 145) residing in the DMRs were subjected to recursive feature elimination to identify CpGs that best distinguish GRAM-score risk. Shown is a hierarchical cluster using the DNA methylation data from the 77 DMPS (see Additional file 1: Table S8), that are shown as a heatmap of the M-values. Low GRAM-score risk (gray) and high GRAM-score risk (black) are indicated. These results indicate that DNA methylation levels at these 77 DMPs may be useful as biomarkers of the severity of COVID-19 patients. (see Additional file 1: Table S6-1 and S6-2)