Evidence map›Paper›PMID 33521749›Full record

ArticleMed (New York, N.Y.)2021

Cell-free DNA tissues of origin by methylation profiling reveals significant cell, tissue, and organ-specific injury related to COVID-19 severity.

Alexandre Pellan Cheng, Matthew Pellan Cheng, Wei Gu, Joan Sesing Lenz, Elaine Hsu, Erwin Schurr, Guillaume Bourque, Mathieu Bourgey, Jerome Ritz, Francisco M Marty and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Med (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
6.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.

  1. Pooled it
  2. Exercise intensity and training alter the innate immune cell type and chromosomal origins of circulating cell-free DNA in humans.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  18. %dd-cfDNA: The New Frontier for Heart/Lung Transplant Surveillance?Transplant international : official journal of the European Society for Organ Transplantation · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 7 institutions in 2 countries.

Alexandre Pellan ChengMeinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Matthew Pellan ChengMcGill University Health Center, Montreal, QC, Canada.
Wei GuDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Joan Sesing LenzMeinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Elaine HsuDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Erwin SchurrDepartment of Human Genetics, McGill University, Montreal, QC, Canada.
Guillaume BourqueDepartment of Human Genetics, McGill University, Montreal, QC, Canada.
Mathieu BourgeyDepartment of Human Genetics, McGill University, Montreal, QC, Canada.
Jerome RitzDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Francisco M MartyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Charles Y ChiuDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Donald C VinhMcGill University Health Center, Montreal, QC, Canada.
Iwijn De VlaminckMeinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Cornell University · USUniversity of California, San Francisco · USMcGill University Health Centre · CAOntario Genomics · CABrigham and Women's Hospital · USHarvard University · USMcGill University · CA

Funding

Pan-Genomic Approaches for Comprehensive Blood Screening of Novel or Emerging Infectious AgentsR01HL105704 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHIU, CHARLES YEN · 2011 to 2020
$5.9M
Epigenetic Profiling of circulating cell-free DNA for the Monitoring of Graft-Versus-Host Disease after Hematopoietic Cell TransplantationR01AI146165 · NIAID · CORNELL UNIVERSITY · PI DE VLAMINCK, IWIJN, RITZ, JEROME · 2020 to 2024
$3.4M
Metagenomic profiling of urinary cell-free DNA to monitor urinary tract infection after kidney transplantationR01AI151059 · NIAID · CORNELL UNIVERSITY · PI DADHANIA, DARSHANA, DE VLAMINCK, IWIJN · 2020 to 2024
$3.4M
The Spatiotemporal Landscape of the Human Brain EpitranscriptomeR01MH117406 · NIMH · WEILL MEDICAL COLL OF CORNELL UNIV · PI MASON, CHRISTOPHER EDWARD · 2018 to 2022
$3.3M
Uncovering associations of variant infection with COVID-19 disease severity in childrenR61HD105618 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHIU, CHARLES YEN, DE VLAMINCK, IWIJN · 2021 to 2022
$3.2M
Precision monitoring of kidney transplants via single-cell and single-molecule sequencingDP2AI138242 · NIAID · CORNELL UNIVERSITY · PI DE VLAMINCK, IWIJN · 2017 to 2017
$2.3M
Noninvasive Risk Stratification of Prostate Cancer Using Cell-Free Nucleic AcidsK08CA230156 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GU, WEI · 2018 to 2022
$1.4M
Identification of diagnostic and prognostic host biomarkers of Zika virus infection by transcriptome profilingR21AI129455 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHIU, CHARLES YEN · 2017 to 2018
$436k
NCI NIH HHS K08 CA230156NHLBI NIH HHS R01 HL105704NIAID NIH HHS DP2 AI138242NIAID NIH HHS R01 AI146165NIAID NIH HHS R01 AI151059NIAID NIH HHS R21 AI129455NIMH NIH HHS R01 MH117406Wellcome Trust
6 · The paper itself

Abstract

backgroundCoronavirus 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.

methodsOur 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.

findingsWe 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.

conclusionsThis study points to the utility of cell-free DNA as an analyte to monitor and study COVID-19.

fundingThis 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.

Indexed as

Cell-Free Nucleic AcidsCOVID-19Virus DiseasesHumansMethylationSARS-CoV-2Cell-Free Nucleic Acidscell-free DNACOVID-19disease severityliquid biopsymethylationSARS-CoV-2tissue injury

Identifiers

PMID33521749
PMCPMC7836424
OpenAlexW3123730963

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.