Detection of the DNA methylation of seven genes contributes to monitoring recovery from COVID-19

Xiao Xiao; Ren Xu; Chaoxiang Du; Jun Yin; Beibei Xin; Zhonghe Ke; Xiyan Li; Hao Zhang; Xinyu Chen

doi:10.3855/jidc.21864

Detection of the DNA methylation of seven genes contributes to monitoring recovery from COVID-19

Authors

Xiao Xiao School of Physics, Changchun University of Science and Technology, Changchun 130022, China
Ren Xu School of Physics, Changchun University of Science and Technology, Changchun 130022, China
Chaoxiang Du Department of Thoracic Surgery, Cancer Center, Zhongshan Hospital of Fudan University, Shanghai, 200030, China
Jun Yin Department of Thoracic Surgery, Cancer Center, Zhongshan Hospital of Fudan University, Shanghai, 200030, China
Beibei Xin Shanghai Rightongene Biotechnology Co Ltd, Shanghai 201403, China
Zhonghe Ke Shanghai Rightongene Biotechnology Co Ltd, Shanghai 201403, China
Xiyan Li Shanghai Rightongene Biotechnology Co Ltd, Shanghai 201403, China
Hao Zhang School of Life Science and Technology, Changchun University of Science and Technology, Changchun 130022, China
Xinyu Chen School of Physics, Changchun University of Science and Technology, Changchun 130022, China https://orcid.org/0009-0006-5057-2682

DOI:

https://doi.org/10.3855/jidc.21864

Keywords:

COVID-19, DNA methylation, flow cytometry, recovery

Abstract

Introduction: DNA methylation might influence the expression of genes that regulate coronavirus disease 2019 (COVID-19) progression. This work explored the significance of DNA methylation of 7 genes (TAC1, CDO1, HOXA9, ZFP42, SOX17, RASSF1A, and SHOX2) in blood circulating free DNA (cfDNA) in differentiating COVID-19 infections and recoveries. The correlation with changes in the proportion of immune cell populations in the recovery period was analyzed.

Methodology: 18 COVID-19-infected, 65 COVID-19-recovered, and 11 uninfected individuals were included. DNA methylation expression was determined by quantitative multiplex methylation-specific PCR (qMSP). The immune function of the recovered group versus uninfected group was evaluated by full-spectrum flow cytometry.

Results: The infected population showed a higher methylation positivity rate for 7 genes compared to the uninfected/recovered population. A model was constructed to distinguish the infected patients from uninfected/recovered individuals using the methylation status of 7 genes, with a sensitivity, specificity and area under curve (AUC) of 0.889, 0.842 and 0.931, respectively. The results of flow cytometry revealed that CD8+ T cells and CD38+ CD8+ T cells were significantly upregulated in recovered individuals compared to those in uninfected individuals. DNA methylation was correlated with immune cell changes, with a significant increase in the percentage of T cells, PD-1+ function CD4+ T cells, TCRγδ+ cells, and CD38+ NKT cells upon an increase in 7 gene methylation positivity.

Conclusions: This work revealed the significance of 7 gene methylation in the diagnosis of COVID-19 recovery, and demonstrated that these genes were significant in evaluating the immune function during the recovery period.

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Published

2026-07-31

How to Cite

Xiao X, Xu R, Du C, Yin J, Xin B, Ke Z, Li X, Zhang H, Chen X (2026) Detection of the DNA methylation of seven genes contributes to monitoring recovery from COVID-19. J Infect Dev Ctries 20:944–953. doi: 10.3855/jidc.21864

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Issue

Vol. 20 No. 07: July 2026

Section

Coronavirus Pandemic

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