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

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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.
Funding Information
  • National Key Research and Development Program of China (2018YFC1200100)
  • National Science and Technology Major Project (2018ZX10301403)
  • the emergency grants for prevention and control of SARS-CoV-2 of Ministries of Science and Technology, and Education of Guangdong province (2020A111128008, 2020B1111320003, 2020KZDZX1158, 2020B1111330001)
  • National Natural Science Foundation of China (32000398, 32171441)
  • Natural Science Foundation of Guangdong Province, China (2017A030306026)
  • Guangdong-Hong Kong Joint Laboratory on Immunological and Genetic Kidney Diseases (2019B121205005)
  • Guangdong Provincial Key Laboratory of Genome Read and Write (2017B030301011)
  • Guangdong Provincial Academician Workstation of BGI Synthetic Genomics (2017B090904014)
  • open project of BGI-Shenzhen (BGIRSZ2020007)

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