{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T20:02:45Z","timestamp":1781380965895,"version":"3.54.1"},"reference-count":84,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","award":["201701091"],"award-info":[{"award-number":["201701091"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Link\u00f6ping University Hospital","award":["COVID-19 ALF"],"award-info":[{"award-number":["COVID-19 ALF"]}]},{"name":"Region \u00d6sterg\u00f6tland ALF","award":["R\u00d6935411"],"award-info":[{"award-number":["R\u00d6935411"]}]},{"name":"Regional ALF Grant 2021"},{"name":"Emory National Primate Research Center","award":["ORIP\/OD P51OD011132"],"award-info":[{"award-number":["ORIP\/OD P51OD011132"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>SARS-CoV-2 infection remains a global health concern, with its impact on host immune responses not fully understood. In a case\u2013control study, we examined how COVID-19 affects DNA methylation patterns in the upper respiratory airway of hospitalized individuals. DNA methylation arrays were performed on nasopharyngeal samples at inclusion\/hospitalization and 6 weeks post-inclusion. We found a distinct DNA methylation pattern in COVID-19 patients compared to healthy controls, identifying 510,099 differentially methylated CpGs. Within the transcription start sites (TSSs) and gene body, COVID-19 patients displayed a higher number of genes\/CpGs with elevated methylation levels. Enrichment analysis of TSS-methylated genes revealed effects of SARS-CoV-2 on genes associated with type I interferons, anti-viral and inflammatory responses, and immune functions. Some CpG methylations were transient, and normalized at group level by 6 weeks post-inclusion. Several IFN-regulated genes, including OAS1, OAS3, IFIT3, and MX1, were identified. Among the top regulators were IL17A and ERK1\/2, both involved in inflammatory processes. Networks nodes included IGF1 and EGF, associated with processes including tissue repair and activation of immune responses. Overall, our data suggests that COVID-19 can impact the upper airway by modifying gene methylation patterns. This could have implications for conditioning of the airways, how individuals respond to future airway infections, and therapeutic interventions.<\/jats:p>","DOI":"10.3390\/cells14211673","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T11:47:19Z","timestamp":1761652039000},"page":"1673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Altered DNA Methylation Pattern Contributes to Differential Epigenetic Immune Signaling in the Upper Respiratory Airway of Unvaccinated COVID-19 Patients"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8327-5517","authenticated-orcid":false,"given":"Melissa","family":"Govender","sequence":"first","affiliation":[{"name":"Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 581 83 Link\u00f6ping, Sweden"},{"name":"Centre for Human Genetics, Pandemic Sciences Institute, University of Oxford, Oxford OX3 7BN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5649-4658","authenticated-orcid":false,"given":"Jyotirmoy","family":"Das","sequence":"additional","affiliation":[{"name":"Bioinformatics, Core Facility, Division of Cell Biology, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Link\u00f6ping University, 581 85 Link\u00f6ping, Sweden"},{"name":"Clinical Genomics Link\u00f6ping, SciLife Laboratory, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 581 83 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis R.","family":"Hopkins","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 581 83 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Svanberg","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 581 83 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5349-2569","authenticated-orcid":false,"given":"Johan","family":"Nordgren","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 581 83 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9770-4623","authenticated-orcid":false,"given":"Marie","family":"Hagbom","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 581 83 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Klingstr\u00f6m","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 581 83 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5719-5601","authenticated-orcid":false,"given":"\u00c5sa","family":"Nilsdotter-Augustinsson","sequence":"additional","affiliation":[{"name":"Division of Infection and Inflammation, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 581 83 Link\u00f6ping, Sweden"},{"name":"Department of Infectious Diseases, Vrinnevi Hospital, 603 79 Norrk\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yean K.","family":"Yong","sequence":"additional","affiliation":[{"name":"Laboratory Centre, Xiamen University Malaysia, Sepang 43900, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4238-1924","authenticated-orcid":false,"given":"Vijayakumar","family":"Velu","sequence":"additional","affiliation":[{"name":"Laboratory Medicine, Department of Pathology, School of Medicine, Emory University, Atlanta, GA 30322, USA"},{"name":"Division of Microbiology and Immunology, Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivadoss","family":"Raju","sequence":"additional","affiliation":[{"name":"State Public Health Laboratory, Directorate of Public Health and Preventive Medicine, DMS Campus, Teynampet, Chennai 600 018, Tamil Nadu, 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