SCIENCE@home

Altered DNA Methylation Pattern Contributes to Differential Epigenetic Immune Signaling in the Upper Respiratory Airway of Unvaccinated COVID-19 Patients

Melissa Govender,Jyotirmoy Das,Francis R. Hopkins,Cecilia Svanberg,Johan Nordgren,M. Hagbom,Jonas Klingström,Åsa Nilsdotter-Augustinsson,Y. Yong,V. Velu,S. Raju,Johanna Sjöwall,E. M. Shankar,Sofi A Nyström,Marie Larsson

Published 2025 in Cells

ABSTRACT

Highlights What are the main findings? COVID-19 patients show a unique DNA methylation profile in the upper airway, with over 510,000 differentially methylated CpGs affecting antiviral, interferon, and immune response genes. Some methylation changes are temporary, normalizing after 6 weeks, while key immune regulators (e.g., IL17A, ERK1/2, OAS1, MX1) remain significantly involved. What is the implication of the main finding? SARS-CoV-2 may reprogram immune and repair pathways in the airways, influencing recovery and susceptibility to future respiratory infections. These findings provide potential targets for biomarkers and therapeutic strategies to modulate post-COVID-19 airway health. Abstract SARS-CoV-2 infection remains a global health concern, with its impact on host immune responses not fully understood. In a case–control 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.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-76 of 76 references · Page 1 of 1

CITED BY

  • No citing papers are available for this paper.

Showing 0-0 of 0 citing papers · Page 1 of 1