Evidence map›Paper›PMID 40170038›Full record

ArticleBMC medical genomics2025

Methylation patterns of the nasal epigenome of hospitalized SARS-CoV-2 positive patients reveal insights into molecular mechanisms of COVID-19.

Benjamin L Spector, Boryana Koseva, Rebecca McLennan, Dithi Banerjee, Kamani Lankachandra, Todd Bradley, Rangaraj Selvarangan, Elin Grundberg

Abstract read
In one paragraph

Article in BMC medical genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Benjamin L SpectorDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI, 53792, USA. bspector2@wisc.edu.
Boryana KosevaDepartment of Pediatrics, Genomic Medicine Center, Children's Mercy Kansas City, 2401 Gillham Rd, Kansas City, MO, 64108, USA.
Rebecca McLennanDepartment of Pediatrics, Genomic Medicine Center, Children's Mercy Kansas City, 2401 Gillham Rd, Kansas City, MO, 64108, USA.
Dithi BanerjeeDepartment of Pathology and Laboratory Medicine, Children'S Mercy Kansas City, 2401 Gillham Rd, Kansas City, MO, 64108, USA.
Kamani LankachandraDepartment of Pathology, University Health, University of Missouri- Kansas City School of Medicine, 2411 Holmes St, Kansas City, MO, 64108, USA.
Todd BradleyDepartment of Pediatrics, Genomic Medicine Center, Children's Mercy Kansas City, 2401 Gillham Rd, Kansas City, MO, 64108, USA.
Rangaraj SelvaranganDepartment of Pathology and Laboratory Medicine, Children'S Mercy Kansas City, 2401 Gillham Rd, Kansas City, MO, 64108, USA.
Elin GrundbergDepartment of Pediatrics, Genomic Medicine Center, Children's Mercy Kansas City, 2401 Gillham Rd, Kansas City, MO, 64108, USA. egrundberg@cmh.edu.

Funding

RADx-UP: Improving the Response of Local Urban and Rural Communities to Disparities in Covid-19 TestingUL1TR002366 · NCATS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Mario Castro, JAMES STEVEN LEEDER · 2017 to 2026
$44.3M
Frontiers Clinical and Translational Science Institute, University of Kansas # UL1TR002366NCATS NIH HHS UL1 TR002366
6 · The paper itself

Abstract

backgroundCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has varied presentations from asymptomatic to death. Efforts to identify factors responsible for differential COVID-19 severity include but are not limited to genome wide association studies (GWAS) and transcriptomic analysis. More recently, variability in host epigenomic profiles have garnered attention, providing links to disease severity. However, whole epigenome analysis of the respiratory tract, the target tissue of SARS-CoV-2, remains ill-defined.

resultsWe interrogated the nasal methylome to identify pathophysiologic drivers in COVID-19 severity through whole genome bisulfite sequencing (WGBS) of nasal samples from COVID-19 positive individuals with severe and mild presentation of disease. We noted differential DNA methylation in intergenic regions and low methylated regions (LMRs), demonstrating the importance of distal regulatory elements in gene regulation in COVID-19 illness. Additionally, we demonstrated differential methylation of pathways implicated in immune cell recruitment and function, and the inflammatory response. We found significant hypermethylation of the FUT4 promoter implicating impaired neutrophil adhesion in severe disease. We also identified hypermethylation of ELF5 binding sites suggesting downregulation of ELF5 targets in the nasal cavity as a factor in COVID-19 phenotypic variability.

conclusionsThis study demonstrated DNA methylation as a marker of the immune response to SARS-CoV-2 infection, with enhancer-like elements playing significant roles. It is difficult to discern whether this differential methylation is a predisposing factor to severe COVID-19, or if methylation differences occur in response to disease severity. These differences in the nasal methylome may contribute to disease severity, or conversely, the nasal immune system may respond to severe infection through differential immune cell recruitment and immune function, and through differential regulation of the inflammatory response.

Indexed as

COVID-19DNA MethylationEpigenomeNasal MucosaSARS-CoV-2AdultAgedEpigenesis, GeneticFemaleHospitalizationHumansMaleMiddle AgedSeverity of Illness IndexCOVID-19EpigenomeMethylationSARS-CoV-2

Identifiers

PMID40170038
PMCPMC11963311

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.