Differential DNA methylation 7 months after SARS-CoV-2 infection

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), and SARS-CoV-2 has been linked to changes in DNA methylation (DNAm) patterns. Studies focused on post-SARS-CoV-2 infection and DNAm have been mainly carried out among severe C...

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Main Authors: Peizhen Hong, Melanie Waldenberger, Michael Pritsch, Leonard Gilberg, Isabel Brand, Jan Bruger, Jonathan Frese, Noemi Castelletti, Mercè Garí, Christof Geldmacher, Michael Hoelscher, Annette Peters, Pamela R. Matías-García, ORCHESTRA-study group
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Clinical Epigenetics
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Online Access:https://doi.org/10.1186/s13148-025-01866-4
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author Peizhen Hong
Melanie Waldenberger
Michael Pritsch
Leonard Gilberg
Isabel Brand
Jan Bruger
Jonathan Frese
Noemi Castelletti
Mercè Garí
Christof Geldmacher
Michael Hoelscher
Annette Peters
Pamela R. Matías-García
ORCHESTRA-study group
author_facet Peizhen Hong
Melanie Waldenberger
Michael Pritsch
Leonard Gilberg
Isabel Brand
Jan Bruger
Jonathan Frese
Noemi Castelletti
Mercè Garí
Christof Geldmacher
Michael Hoelscher
Annette Peters
Pamela R. Matías-García
ORCHESTRA-study group
author_sort Peizhen Hong
collection DOAJ
description Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), and SARS-CoV-2 has been linked to changes in DNA methylation (DNAm) patterns. Studies focused on post-SARS-CoV-2 infection and DNAm have been mainly carried out among severe COVID-19 cases or without distinguishing the severity of cases. However, investigations into mild and asymptomatic cases after SARS-CoV-2 infection are limited. In this study, we analyzed DNAm patterns of mild and asymptomatic cases seven months after SARS-CoV-2 infection in a household setting by conducting epigenome-wide association studies (EWAS). Results We identified DNAm changes at 42 CpG sites associated with anti-SARS-CoV-2 antibody levels. We additionally report EWAS between COVID-19 cases and controls, with the case status being confirmed by either an antibody test or a PCR test. The EWAS with an antibody test case definition identified 172 CpG sites to be differentially methylated, while the EWAS with a PCR test case definition identified 502 CpG sites. Two common sites, namely cg17126990 (annotated to AFAP1L2) and cg25483596 (annotated to PC), were identified to be hypermethylated across the three EWAS. Both CpG sites have been reported to be involved in molecular pathways after SARS-CoV-2 infection. While AFAP1L2 has been found to be upregulated after SARS-CoV-2 infection, the pyruvate carboxylase (PC) activity seems to be affected by SARS-CoV-2 infection resulting in changes to the host cell metabolism. Additionally, an EWAS to assess persistent health restrictions among PCR-confirmed cases showed 40 CpG sites to be differentially methylated. Conclusions We detected associations between DNAm in individuals who had asymptomatic and mild SARS-CoV-2 infections as compared to their household controls. These findings contribute to our understanding of the molecular consequences of SARS-CoV-2 infection observed months after infection.
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spelling doaj-art-bb03b0e79004486a9a55ba8cc197bfd82025-08-20T02:28:08ZengBMCClinical Epigenetics1868-70832025-04-0117111110.1186/s13148-025-01866-4Differential DNA methylation 7 months after SARS-CoV-2 infectionPeizhen Hong0Melanie Waldenberger1Michael Pritsch2Leonard Gilberg3Isabel Brand4Jan Bruger5Jonathan Frese6Noemi Castelletti7Mercè Garí8Christof Geldmacher9Michael Hoelscher10Annette Peters11Pamela R. Matías-García12ORCHESTRA-study groupResearch Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental HealthResearch Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental HealthInstitute of Infectious Diseases and Tropical Medicine, LMU University Hospital, LMU MunichInstitute of Infectious Diseases and Tropical Medicine, LMU University Hospital, LMU MunichInstitute of Infectious Diseases and Tropical Medicine, LMU University Hospital, LMU MunichInstitute of Infectious Diseases and Tropical Medicine, LMU University Hospital, LMU MunichInstitute of Infectious Diseases and Tropical Medicine, LMU University Hospital, LMU MunichInstitute of Infectious Diseases and Tropical Medicine, LMU University Hospital, LMU MunichInstitute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental HealthInstitute of Infectious Diseases and Tropical Medicine, LMU University Hospital, LMU MunichInstitute of Infectious Diseases and Tropical Medicine, LMU University Hospital, LMU MunichResearch Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental HealthResearch Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental HealthAbstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), and SARS-CoV-2 has been linked to changes in DNA methylation (DNAm) patterns. Studies focused on post-SARS-CoV-2 infection and DNAm have been mainly carried out among severe COVID-19 cases or without distinguishing the severity of cases. However, investigations into mild and asymptomatic cases after SARS-CoV-2 infection are limited. In this study, we analyzed DNAm patterns of mild and asymptomatic cases seven months after SARS-CoV-2 infection in a household setting by conducting epigenome-wide association studies (EWAS). Results We identified DNAm changes at 42 CpG sites associated with anti-SARS-CoV-2 antibody levels. We additionally report EWAS between COVID-19 cases and controls, with the case status being confirmed by either an antibody test or a PCR test. The EWAS with an antibody test case definition identified 172 CpG sites to be differentially methylated, while the EWAS with a PCR test case definition identified 502 CpG sites. Two common sites, namely cg17126990 (annotated to AFAP1L2) and cg25483596 (annotated to PC), were identified to be hypermethylated across the three EWAS. Both CpG sites have been reported to be involved in molecular pathways after SARS-CoV-2 infection. While AFAP1L2 has been found to be upregulated after SARS-CoV-2 infection, the pyruvate carboxylase (PC) activity seems to be affected by SARS-CoV-2 infection resulting in changes to the host cell metabolism. Additionally, an EWAS to assess persistent health restrictions among PCR-confirmed cases showed 40 CpG sites to be differentially methylated. Conclusions We detected associations between DNAm in individuals who had asymptomatic and mild SARS-CoV-2 infections as compared to their household controls. These findings contribute to our understanding of the molecular consequences of SARS-CoV-2 infection observed months after infection.https://doi.org/10.1186/s13148-025-01866-4COVID-19SARS-CoV-2Epigenome-wide association studyDNA methylation
spellingShingle Peizhen Hong
Melanie Waldenberger
Michael Pritsch
Leonard Gilberg
Isabel Brand
Jan Bruger
Jonathan Frese
Noemi Castelletti
Mercè Garí
Christof Geldmacher
Michael Hoelscher
Annette Peters
Pamela R. Matías-García
ORCHESTRA-study group
Differential DNA methylation 7 months after SARS-CoV-2 infection
Clinical Epigenetics
COVID-19
SARS-CoV-2
Epigenome-wide association study
DNA methylation
title Differential DNA methylation 7 months after SARS-CoV-2 infection
title_full Differential DNA methylation 7 months after SARS-CoV-2 infection
title_fullStr Differential DNA methylation 7 months after SARS-CoV-2 infection
title_full_unstemmed Differential DNA methylation 7 months after SARS-CoV-2 infection
title_short Differential DNA methylation 7 months after SARS-CoV-2 infection
title_sort differential dna methylation 7 months after sars cov 2 infection
topic COVID-19
SARS-CoV-2
Epigenome-wide association study
DNA methylation
url https://doi.org/10.1186/s13148-025-01866-4
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