Blood DNA methylation in post-acute sequelae of COVID-19 (PASC): a prospective cohort study

作者：Joseph Balnis, Andy Madrid, Lisa A. Drake, Rachel Vancavage, Anupama Tiwari, Vraj Patel, Ramon Bossardi Ramos, John J. Schwarz, Recai Yucel, Harold A. Singer, Reid S. Alisch, Ariel Jaitovich · 发表于：EBioMedicine · 年份：2024 · DOI：10.1016/j.ebiom.2024.105251 · 被引用次数：27 · 研究领域：Epigenetics and DNA Methylation、Immune responses and vaccinations、Long-Term Effects of COVID-19

BACKGROUND: DNA methylation integrates environmental signals with transcriptional programs. COVID-19 infection induces changes in the host methylome. While post-acute sequelae of COVID-19 (PASC) is a long-term complication of acute illness, its association with DNA methylation is unknown. No universal blood marker of PASC, superseding single organ dysfunctions, has yet been identified. METHODS: In this single centre prospective cohort study, PASC, post-COVID without PASC, and healthy participants were enrolled to investigate their symptoms association with peripheral blood DNA methylation data generated with state-of-the-art whole genome sequencing. PASC-induced quality-of-life deterioration was scored with a validated instrument, SF-36. Analyses were conducted to identify potential functional roles of differentially methylated loci, and machine learning algorithms were used to resolve PASC severity. FINDINGS: 103 patients with PASC (22.3% male, 77.7% female), 15 patients with previous COVID-19 infection but no PASC (40.0% male, 60.0% female), and 27 healthy volunteers (48.1% male, 51.9% female) were enrolled. Whole genome methylation sequencing revealed 39 differentially methylated regions (DMRs) specific to PASC, each harbouring an average of 15 consecutive positions, that differentiate patients with PASC from the two control groups. Motif analyses of PASC-regulated DMRs identify binding domains for transcription factors regulating circadian rhythm and others. Some DMRs ann...