Whole blood DNA methylation analysis reveals respiratory environmental traits involved in COVID-19 severity following SARS-CoV-2 infection

Guillermo Barturen (), Elena Carnero-Montoro, Manuel Martínez-Bueno, Silvia Rojo-Rello, Beatriz Sobrino, Óscar Porras-Perales, Clara Alcántara-Domínguez, David Bernardo and Marta E. Alarcón-Riquelme ()
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Guillermo Barturen: GENYO. Center for Genomics and Oncological Research Pfizer/University of Granada/Andalusian Regional Government
Elena Carnero-Montoro: GENYO. Center for Genomics and Oncological Research Pfizer/University of Granada/Andalusian Regional Government
Manuel Martínez-Bueno: GENYO. Center for Genomics and Oncological Research Pfizer/University of Granada/Andalusian Regional Government
Silvia Rojo-Rello: Hospital Clínico Universitario de Valladolid
Beatriz Sobrino: Hospital Regional de Málaga
Óscar Porras-Perales: Hospital Regional de Málaga
Clara Alcántara-Domínguez: Lorgen G.P., S.L., Business Innovation Center - BIC/CEEL, Technological Area of Health Science
David Bernardo: Mucosal Immunology Lab. Unidad de Excelencia Instituto de Biomedicina y Genética Molecular de Valladolid (IBGM, Universidad de Valladolid-CSIC)
Marta E. Alarcón-Riquelme: GENYO. Center for Genomics and Oncological Research Pfizer/University of Granada/Andalusian Regional Government

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract SARS-CoV-2 infection can cause an 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 aim to evaluate the implication of DNA methylation in COVID-19 progression by means of a genome-wide DNA methylation analysis combined with DNA genotyping. The results reveal the existence of epigenomic regulation of functional pathways associated with COVID-19 progression and mediated by genetic loci. We find an environmental trait-related signature that discriminates mild from severe cases and regulates, among other cytokines, IL-6 expression via the transcription factor CEBP. 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.

Date: 2022
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DOI: 10.1038/s41467-022-32357-2

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