Genome-wide H3K4me3 profiling of circulating immune cells reveals dynamic epigenetic reprogramming during acute critical COVID-19

Epigenetic mechanisms, particularly changes in H3K4me3 enrichment at gene promoters, have been observed in immune tolerance and monocyte dysfunction in sepsis. Whether comparable H3K4me3 alterations occur during acute critical COVID-19 illness has not been investigated.

Among 706 differentially bound consensus peaks with promoter association between ICU and non-ICU groups, 704 showed increased H3K4me3 occupancy in ICU patients, predominantly at neutrophil effector gene loci, supported by pathway enrichment of neutrophil degranulation and innate immune activation. Monocyte HLA-DR expression and ex vivo TLR-stimulated IL-6 secretion were persistently reduced throughout the first week of ICU treatment.