Cell-Free DNA Tissues-of-Origin by Methylation Profiling Reveals Significant Cell, Tissue and Organ-Specific injury related to COVID-19 Severity

Cheng, Alexandre Pellan; Cheng, Matthew Pellan; Gu, Wei; Lenz, Joan Sesing; Hsu, Elaine; Schurr, Erwin; Bourque, Guillaume; Bourgey, Mathieu; Ritz, Jerome; Marty, Francisco M.; Chiu, Charles Y.; Vinh, Donald Cuong; De Vlaminck, Iwijn

Background COVID-19 primarily affects the lungs, but evidence of systemic disease with multi-organ involvement is emerging. Here, we developed a blood test to broadly quantify cell, tissue, and organ specific injury due to COVID-19. Methods Our test leverages genome-wide methylation profiling of circulating cell-free DNA in plasma. We assessed the utility of this test to identify subjects with severe disease in two independent, longitudinal cohorts of hospitalized patients. Cell-free DNA profiling was performed on 104 plasma samples from 33 COVID-19 patients and compared to samples from patients with other viral infections and healthy controls. Findings We found evidence of injury to the lung and liver and involvement of red blood cell progenitors associated with severe COVID-19. The concentration of cell-free DNA correlated with the WHO ordinal scale for disease progression and was significantly increased in patients requiring intubation. Conclusion This study points to the utility of cell-free DNA as an analyte to monitor and study COVID-19.