Whole-Blood DNA Methylation Analysis Reveals Respiratory Environmental Traits Involved in COVID-19 Severity Following SARS-CoV-2 Infection and Common Molecular Signatures with Autoimmune Diseases

Guillermo Barturen¹, Elena Carnero-Montoro¹, Manuel Martinez-Bueno¹, Silvia Rojo-Rello², Beatriz Sobrino³, Clara Alcántara-Domínguez⁴, David Bernardo⁵ and Marta Alarcon-Riquelme¹, ¹Center for Genomics and Oncological Research (GENYO), Granada, Spain, ²Hospital Clínico Universitario, Valladolid, Spain, ³Hospital Regional de Málaga, Málaga, Spain, ⁴Lorgen G.P., SL, Granada, Spain, ⁵Universidad de Valladolid-CSIC, Valladolid, Spain

Meeting: ACR Convergence 2022

Keywords: autoimmune diseases, Bioinformatics, COVID-19, Environmental factors, Epigenetics

Session Information

Date: Sunday, November 13, 2022

Title: Genetics, Genomics and Proteomics Poster

Session Type: Poster Session C

Session Time: 1:00PM-3:00PM

Background/Purpose: SARS-CoV-2 causes a severe inflammatory syndrome (COVID-19) leading, in many cases, to bilateral pneumonia, severe dyspnea and in ~5% of these, death. DNA methylation is known to play an important role in the regulation of the immune processes behind COVID-19 progression, however it has not been studied in depth. In this study, we aimed at evaluating the implication of DNA methylation in COVID-19 progression and the extent to which COVID19-associated epigenetic signals are also observed in rheumatic autoimmune diseases.

Methods: We performed a genome-wide DNA methylation analysis on COVID19 positivity and severity by linear regression models in whole blood samples from SARS-CoV-2 RT-PCR negative (N=101) and positive lab tested individuals (N=473) obtained from two clinical Spanish centers. We followed up COVID-19-associated differentially methylated sites (DMS) by performing functional enrichment analyses, discovery of methylation correlated modules, methylation quantitative trait locus (meQTL) mapping and contrasting epigenetic signals with publicly available single-cell RNAseq COVID19 information. We searched for COVID19-associated epigenetic signals on data obtained from systemic autoimmune diseases (SADs) from the PRECISESADS project.

Results: The results revealed the existence of epigenomic regulation of functional pathways associated with COVID-19 severity and mediated by genetic loci with similarities with autoimmune disease pathways. We found an environmental trait-related signature that discriminates mild from severe cases, and regulates IL-6 expression via the transcription factor CEBP.

Conclusion: The analyses suggest that an interaction between environmental contribution, genetics and epigenetics might be playing a role in triggering the cytokine storm described in the most severe cases. Our findings also reveal common dysregulated pathways between COVID19 and SADs but also important differences regarding the environmental related signature.

Disclosures: G. Barturen, None; E. Carnero-Montoro, None; M. Martinez-Bueno, None; S. Rojo-Rello, None; B. Sobrino, None; C. Alcántara-Domínguez, None; D. Bernardo, None; M. Alarcon-Riquelme, None.

To cite this abstract in AMA style:

Barturen G, Carnero-Montoro E, Martinez-Bueno M, Rojo-Rello S, Sobrino B, Alcántara-Domínguez C, Bernardo D, Alarcon-Riquelme M. Whole-Blood DNA Methylation Analysis Reveals Respiratory Environmental Traits Involved in COVID-19 Severity Following SARS-CoV-2 Infection and Common Molecular Signatures with Autoimmune Diseases [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9). https://acrabstracts.org/abstract/whole-blood-dna-methylation-analysis-reveals-respiratory-environmental-traits-involved-in-covid-19-severity-following-sars-cov-2-infection-and-common-molecular-signatures-with-autoimmune-diseases/. Accessed .

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