Cell-free DNA tissues of origin by methylation profiling reveals significant cell, tissue, and organ-specific injury related to COVID-19 severity.
Med (N Y)
; 2(4): 411-422.e5, 2021 04 09.
Article
in English
| MEDLINE | ID: covidwho-1033380
ABSTRACT
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Virus Diseases
/
Cell-Free Nucleic Acids
/
COVID-19
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
Med (N Y)
Year:
2021
Document Type:
Article
Affiliation country:
J.medj.2021.01.001
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