Blood DNA methylation and COVID-19 outcomes

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Abstract

Background

There are no prior reports that compare differentially methylated regions of DNA in blood samples from COVID-19 patients to samples collected before the SARS-CoV-2 pandemic using a shared epigenotyping platform. We performed a genome-wide analysis of circulating blood DNA CpG methylation using the Infinium Human MethylationEPIC BeadChip on 124 blood samples from hospitalized COVID-19-positive and COVID-19-negative patients and compared these data with previously reported data from 39 healthy individuals collected before the pandemic. Prospective outcome measures such as COVID-19-GRAM risk-score and mortality were combined with methylation data.

Results

Global mean methylation levels did not differ between COVID-19 patients and healthy pre-pandemic controls. About 75% of acute illness-associated differentially methylated regions were located near gene promoter regions and were hypo-methylated in comparison with healthy pre-pandemic controls. Gene ontology analyses revealed terms associated with the immune response to viral infections and leukocyte activation; and disease ontology analyses revealed a predominance of autoimmune disorders. Among COVID-19-positive patients, worse outcomes were associated with a prevailing hyper-methylated status. Recursive feature elimination identified 77 differentially methylated positions predictive of COVID-19 severity measured by the GRAM-risk score.

Conclusion

Our data contribute to the awareness that DNA methylation may influence the expression of genes that regulate COVID-19 progression and represent a targetable process in that setting.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13148-021-01102-9.

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Most cited references 87

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Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Fei Zhou, Ting Yu, Ronghui Du … (2020)

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

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clusterProfiler: an R package for comparing biological themes among gene clusters.

Guangchuang Yu, Li-Gen Wang, Yanyan Han … (2012)

Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis. Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters. The analysis module and visualization module were combined into a reusable workflow. Currently, clusterProfiler supports three species, including humans, mice, and yeast. Methods provided in this package can be easily extended to other species and ontologies. The clusterProfiler package is released under Artistic-2.0 License within Bioconductor project. The source code and vignette are freely available at http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.

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Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

Dawei Wang, Bo Hu, Fangfang Zhu … (2020)

In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.

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Author and article information

Contributors

Reid S. Alisch: alisch@neurosurgery.wisc.edu

Ariel Jaitovich:

ORCID: http://orcid.org/0000-0003-4714-2260

jaitova@amc.edu

Journal

Journal ID (nlm-ta): Clin Epigenetics

Journal ID (iso-abbrev): Clin Epigenetics

Title: Clinical Epigenetics

Publisher: BioMed Central (London )

ISSN (Print): 1868-7075

ISSN (Electronic): 1868-7083

Publication date (Electronic): 25 May 2021

Publication date PMC-release: 25 May 2021

Publication date Collection: 2021

Volume: 13

Electronic Location Identifier: 118

Affiliations

[1 ]GRID grid.413558.e, ISNI 0000 0001 0427 8745, Division of Pulmonary and Critical Care Medicine, , Albany Medical Center, ; Albany, NY USA

[2 ]GRID grid.413558.e, ISNI 0000 0001 0427 8745, Department of Molecular and Cellular Physiology, , Albany Medical College, ; Albany, NY USA

[3 ]GRID grid.28803.31, ISNI 0000 0001 0701 8607, Department of Neurological Surgery, , University of Wisconsin, ; Madison, WI USA

[4 ]GRID grid.28803.31, ISNI 0000 0001 0701 8607, Department of Anesthesiology, , University of Wisconsin, ; Madison, WI USA

[5 ]GRID grid.413558.e, ISNI 0000 0001 0427 8745, Department of Immunology and Microbial Disease, , Albany Medical College, ; Albany, NY USA

Author information

Ariel Jaitovich http://orcid.org/0000-0003-4714-2260

Article

Publisher ID: 1102

DOI: 10.1186/s13148-021-01102-9

PMC ID: 8148415

PubMed ID: 34034806

SO-VID: f8c6a8bf-2854-4676-9a4f-7902d1aee734

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 2 March 2021

Date accepted : 11 May 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;

Award ID: K01HL130704

Award ID: R01HL049426

Award Recipient : Harold A. Singer Ariel Jaitovich

Funded by: FundRef http://dx.doi.org/10.13039/100000049, National Institute on Aging;

Award ID: R01AG066179

Award Recipient : Reid S. Alisch

Custom metadata

ScienceOpen disciplines: Genetics

Keywords: covid-19,dna methylation,mortality,outcomes,acute respiratory distress syndrome (ards),gene expression

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ScienceOpen disciplines: Genetics

Keywords: covid-19, dna methylation, mortality, outcomes, acute respiratory distress syndrome (ards), gene expression

Blood DNA methylation and COVID-19 outcomes

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Novel Coronavirus Disease COVID-19

Most cited references 87

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

clusterProfiler: an R package for comparing biological themes among gene clusters.

Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

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