Cell-Free DNA in Blood Reveals Significant Cell, Tissue and Organ Specific injury and Predicts COVID-19 Severity

Background Coronavirus disease 2019 (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 World Health Organization (WHO) ordinal scale for disease progression and was significantly increased in patients requiring intubation. Conclusions This study points to the utility of cell-free DNA as an analyte to monitor and study COVID-19. Funding This work was supported by NIH grants 1DP2AI138242 (to I.D.V.), R01AI146165 (to I.D.V., M.P.C., F.M.M., and J.R.), 1R01AI151059 (to I.D.V.), K08-CA230156 (to W.G.), and R33-AI129455 to C.Y.C., a Synergy award from the Rainin Foundation (to I.D.V.), a SARS-CoV-2 seed grant at Cornell (to I.D.V.), a National Sciences and Engineering Research Council of Canada fellowship PGS-D3 (to A.P.C.), and a Burroughs-Wellcome CAMS Award (to W.G.). D.C.V. is supported by a Fonds de la Recherche en Sante du Quebec Clinical Research Scholar Junior 2 award. C.Y.C. is supported by the California Initiative to Advance Precision Medicine, and the Charles and Helen Schwab Foundation.
Graphical Abstract
Context and Significance COVID-19 is a systemic disease with multi-organ involvement. Here, the authors report a blood test to quantify cell-, tissue-, and organ-specific injury due to COVID-19. This is accomplished by profiling methylation marks within circulating cell-free DNA (cfDNA) to trace their tissues of origin and to quantify tissue-specific injury due to COVID-19. The authors assessed the utility of this test to identify subjects with severe disease in two independent, longitudinal cohorts of hospitalized patients and report evidence of injury to the lung and liver and involvement of red blood cell progenitors associated with severe COVID-19. These results support the utility of cfDNA profiling as a prognostic tool for the early detection and monitoring of cell and tissue injury due to COVID-19.
COVID-19 affects the entire body. Cheng et al. describe a DNA-based blood test to quantify cell and tissue injury due to COVID-19. They show that severe COVID-19 is associated with increased lung, liver, and erythroblast DNA in blood and that the concentration of cell-free DNA correlates with disease progression.