Symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. A deep understanding of the variation of biological characteristics in severe COVID-19 patients is crucial for the detection of individuals at high risk of critical condition for the clinical management of the disease. Herein, by profiling the gene expression spectrum deduced from DNA coverage in regions surrounding transcriptional start site in plasma cell-free DNA (cfDNA) of COVID-19 patients, we deciphered the altered biological processes in the severe cases and demonstrated the feasibility of cfDNA in measuring the COVID-19 progression. The up- and downregulated genes in the plasma of severe patient were found to be closely related to the biological processes and functions affected by COVID-19 progression. More importantly, with the analysis of transcriptome data of blood cells and lung cells from control group and cases with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, we revealed that the upregulated genes were predominantly involved in the viral and antiviral activity in blood cells, reflecting the intense viral replication and the active reaction of immune system in the severe patients. Pathway analysis of downregulated genes in plasma DNA and lung cells also demonstrated the diminished adenosine triphosphate synthesis function in lung cells, which was evidenced to correlate with the severe COVID-19 symptoms, such as a cytokine storm and acute respiratory distress. Overall, this study revealed tissue involvement, provided insights into the mechanism of COVID-19 progression, and highlighted the utility of cfDNA as a noninvasive biomarker for disease severity inspections.
【저자키워드】 SARS-CoV-2, COVID-19 severity, plasma DNA, TSS coverage, tissue specificity, 【초록키워드】 COVID-19, coronavirus disease, Transcriptome, Cytokine storm, Biomarker, Gene Expression, feasibility, disease severity, Variation, Infection, Blood cells, immune system, antiviral activity, DNA, Region, Coverage, Characteristics, Asymptomatic, viral replication, death, Clinical management, plasma, Severe patient, severe pneumonia, utility, mechanism, function, COVID-19 patients, acute respiratory distress, Analysis, noninvasive, high risk, cfDNA, cell-free DNA, blood cell, COVID-19 progression, control group, severe patients, tissue, individual, Severe case, critical condition, lung cells, severe COVID-19 symptoms, upregulated gene, lung cell, transcriptional, affected, involved, the disease, provided, demonstrated, evidenced, biological processe, downregulated gene, severe COVID-19 patient, 【제목키워드】 COVID-19, DNA, Site,