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Plasma cell-free DNA promise monitoring and tissue injury assessment of COVID-19.

ABSTRACT: Coronavirus 2019 (COVID-19) is a complex disease that affects billions of people worldwide. Currently, effective etiological treatment of COVID-19 is still lacking; COVID-19 also causes damages to various organs that affects therapeutics and mortality of the patients. Surveillance of the treatment responses and organ injury assessment of COVID-19 patients are of high clinical value. In this study, we investigated the characteristic fragmentation patterns and explored the potential in tissue injury assessment of plasma cell-free DNA in COVID-19 patients. Through recruitment of 37 COVID-19 patients, 32 controls and analysis of 208 blood samples upon diagnosis and during treatment, we report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA fragmentation characteristics reflect patient-specific physiological changes during treatment. Further analysis on cfDNA tissue-of-origin tracing reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, our work demonstrates and extends the translational merit of cfDNA fragmentation pattern as valuable analyte for effective treatment monitoring, as well as tissue injury assessment in COVID-19.

SUBMITTER: Jin X

PROVIDER: S-EPMC10104435 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Plasma cell-free DNA promise monitoring and tissue injury assessment of COVID-19.

Jin Xin X Wang Yanqun Y Xu Jinjin J Li Yimin Y Cheng Fanjun F Luo Yuxue Y Zhou Haibo H Lin Shanwen S Xiao Fei F Zhang Lu L Lin Yu Y Zhang Zhaoyong Z Jin Yan Y Zheng Fang F Chen Wei W Zhu Airu A Tao Ye Y Zhao Jingxian J Kuo Tingyou T Li Yuming Y Li Lingguo L Wen Liyan L Ou Rijing R Li Fang F Lin Long L Zhang Yanjun Y Sun Jing J Yuan Hao H Zhuang Zhen Z Sun Haixi H Chen Zhao Z Li Jie J Zhuo Jianfen J Chen Dongsheng D Zhang Shengnan S Sun Yuzhe Y Wei Peilan P Yuan Jinwei J Xu Tian T Yang Huanming H Wang Jian J Xu Xun X Zhong Nanshan N Xu Yonghao Y Sun Kun K Zhao Jincun J

Molecular genetics and genomics : MGG 20230414 4

Coronavirus 2019 (COVID-19) is a complex disease that affects billions of people worldwide. Currently, effective etiological treatment of COVID-19 is still lacking; COVID-19 also causes damages to various organs that affects therapeutics and mortality of the patients. Surveillance of the treatment responses and organ injury assessment of COVID-19 patients are of high clinical value. In this study, we investigated the characteristic fragmentation patterns and explored the potential in tissue inju ...[more]

PMID: 37059908

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Project description:BackgroundThe recently identified methylation patterns specific to cell type allows the tracing of cell death dynamics at the cellular level in health and diseases. This study used COVID-19 as a disease model to investigate the efficacy of cell-specific cell-free DNA (cfDNA) methylation markers in reflecting or predicting disease severity or outcome.MethodsWhole genome methylation sequencing of cfDNA was performed for 20 healthy individuals, 20 cases with non-hospitalized COVID-19 and 12 cases with severe COVID-19 admitted to intensive care unit (ICU). Differentially methylated regions (DMRs) and gene ontology pathway enrichment analyses were performed to explore the locus-specific methylation difference between cohorts. The proportion of cfDNA derived from lung and immune cells to a given sample (i.e. tissue fraction) at cell-type resolution was estimated using a novel algorithm, which reflects lung injuries and immune response in COVID-19 patients and was further used to evaluate clinical severity and patient outcome.ResultsCOVID‑19 patients had globally reduced cfDNA methylation level compared with healthy controls. Compared with non-hospitalized COVID-19 patients, the cfDNA methylation pattern was significantly altered in severe patients with the identification of 11,156 DMRs, which were mainly enriched in pathways related to immune response. Markedly elevated levels of cfDNA derived from lung and more specifically alveolar epithelial cells, bronchial epithelial cells, and lung endothelial cells were observed in COVID-19 patients compared with healthy controls. Compared with non-hospitalized patients or healthy controls, severe COVID-19 had significantly higher cfDNA derived from B cells, T cells and granulocytes and lower cfDNA from natural killer cells. Moreover, cfDNA derived from alveolar epithelial cells had the optimal performance to differentiate COVID-19 with different severities, lung injury levels, SOFA scores and in-hospital deaths, with the area under the receiver operating characteristic curve of 0.958, 0.941, 0.919 and 0.955, respectively.ConclusionSevere COVID-19 has a distinct cfDNA methylation signature compared with non-hospitalized COVID-19 and healthy controls. Cell type-specific cfDNA methylation signature enables the tracing of COVID-19 related cell deaths in lung and immune cells at cell-type resolution, which is correlated with clinical severities and outcomes, and has extensive application prospects to evaluate tissue injuries in diseases with multi-organ dysfunction.

Dataset Information

Plasma cell-free DNA promise monitoring and tissue injury assessment of COVID-19.

Publications

Plasma cell-free DNA promise monitoring and tissue injury assessment of COVID-19.

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