COVID-19重症度に関連する古典的単球表現型における主要な調節因子の発見：単一細胞マルチオミクスシーケンシングを用いて

Dysregulated immune responses often accompany severe COVID-19, but the underlying epigenetic mechanisms driving monocyte heterogeneity and COVID-19 progression remain unclear. Here, we applied single-cell multi-omics profiling to peripheral blood mononuclear cells across healthy and four COVID-19 severity stages. We identified two severity-associated classical monocyte subtypes-IL7R+ and CD163+, These subtypes exhibit distinct transcriptional and epigenetic landscapes. By constructing a gene regulatory network and in silico perturbations, we revealed that ETS1 is a key driver of IL7R + monocytes with T cell-like signaling features and that JDP2 is a repressor that maintains the profibrotic, anti-inflammatory identity of CD163+ monocytes by suppressing AP-1 activity. These subtypes were enriched in the moderate-to-critical stages and exhibited signaling pathways associated with tissue remodeling and immune suppression. Our findings define monocyte heterogeneity as linked to COVID-19 severity and identify ETS1 and JDP2 as central regulators, offering insights into immune dysregulation, potential therapeutic targets for fibrosis, and long-term sequelae.