Whole-Blood DNA Methylation Analysis Reveals Respiratory Environmental Traits Involved in COVID-19 Severity Following SARS-CoV-2 Infection

Abstract

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, yet. 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 found an environmental trait-related signature that discriminates mild from severe cases, and regulates 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. ; This work has been supported through Consejería de Transformación Económica, Industria, Conocimiento y Universidades of the regional government of Andalucía cofounded by the European Union through European Regional Development Fund (FEDER, CV20-10150), Consejo Superior de Investigaciones científicas (CSIC-COV19-016/202020E155) and Junta de Castilla y León (Proyectos COVID 07.04.467B04.74011.0 and IBGM excellence programme CLU-2029-02). G.B. is supported by the Instituto de Salud Carlos III (ISCIII, Spanish Health Ministry) through the Sara Borrell subprogram (CD18/00153). ; Peer reviewed