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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.
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1 BGI-Shenzhen, Shenzhen, China (GRID:grid.21155.32) (ISNI:0000 0001 2034 1839); South China University of Technology, School of Medicine, Guangzhou, China (GRID:grid.79703.3a) (ISNI:0000 0004 1764 3838)
2 The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China (GRID:grid.470124.4)
3 BGI-Shenzhen, Shenzhen, China (GRID:grid.21155.32) (ISNI:0000 0001 2034 1839)
4 Huazhong University of Science and Technology, Union Hospital, Tongji Medical College, Wuhan, China (GRID:grid.33199.31) (ISNI:0000 0004 0368 7223)
5 The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, China (GRID:grid.410737.6) (ISNI:0000 0000 8653 1072)
6 Yangjiang People’s Hospital, Yangjiang, China (GRID:grid.410737.6)
7 The Fifth Affiliated Hospital, Sun Yat-Sen University, Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Biomedical Imaging, Guangdong Provincial Engineering Research Center of Molecular Imaging, Zhuhai, China (GRID:grid.452859.7) (ISNI:0000 0004 6006 3273)
8 Guangzhou Eighth People’s Hospital of Guangzhou Medical University, Institute of Infectious Disease, Guangzhou, China (GRID:grid.413419.a) (ISNI:0000 0004 1757 6778)
9 South China University of Technology, School of Medicine, Guangzhou, China (GRID:grid.79703.3a) (ISNI:0000 0004 1764 3838)
10 BGI-Shenzhen, Shenzhen, China (GRID:grid.21155.32) (ISNI:0000 0001 2034 1839); University of Chinese Academy of Sciences, BGI Education Center, Shenzhen, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419)
11 BGI-Shenzhen, Shenzhen, China (GRID:grid.21155.32) (ISNI:0000 0001 2034 1839); BGI-Shenzhen, Guangdong Provincial Academician Workstation of BGI Synthetic Genomics, Shenzhen, China (GRID:grid.21155.32) (ISNI:0000 0001 2034 1839)
12 BGI-Shenzhen, Shenzhen, China (GRID:grid.21155.32) (ISNI:0000 0001 2034 1839); BGI-Shenzhen, Guangdong Provincial Key Laboratory of Genome Read and Write, Shenzhen, China (GRID:grid.21155.32) (ISNI:0000 0001 2034 1839)
13 Shenzhen Bay Laboratory, Institute of Cancer Research, Shenzhen, China (GRID:grid.510951.9) (ISNI:0000 0004 7775 6738)
14 The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China (GRID:grid.470124.4); Guangzhou Eighth People’s Hospital of Guangzhou Medical University, Institute of Infectious Disease, Guangzhou, China (GRID:grid.413419.a) (ISNI:0000 0004 1757 6778)