講演情報
[OE5-3]日本人における大規模scRNA-seqを用いたCOVID-19重症化の生物学的・宿主遺伝学的メカニズムの解明
○枝廣 龍哉1, 白井 雄也1, 竹島 雄介2, 榊原 修平2, 山口 勇太1,2, 村上 輝明1,2, 森田 貴義1,2, 加藤 保宏1,2, 劉 祐誠2, 元岡 大祐2, 多久和 綾子2, Wing James2, 曽根原 究人1,3,4, Japan COVID-19 Task Force, 南宮 湖5, 田中 拓5, 李 昊5, 福永 興壱5, 平田 陽彦1, 武田 吉人1, 奥崎 大介2, 熊ノ郷 淳1,2, 岡田 随象1,2,3,4 (1.大阪大学大学院医学系研究科, 2.大阪大学免疫学フロンティア研究センター, 3.東京大学大学院医学系研究科, 4.理化学研究所生命医科学研究センター, 5.慶應義塾大学医学部)
While multiple studies have highlighted dysregulation of complex networks of peripheral blood immune responses in COVID-19 using single-cell RNA-sequencing (scRNA-seq) analysis, the immune response of the host to SARS-CoV-2 still remains unclear. We analyzed single-cell transcriptome and T/B cell receptor of over 600,000 peripheral blood mononuclear cells from COVID-19 patients and healthy controls of Japanese ancestry with host genetics data. Differential abundance analysis revealed that the proportion of non-classical monocytes (ncMono) decreased in COVID-19 patients. RNA velocity analysis identified the downregulation of the cell transition from classical monocytes to ncMono in COVID-19 patients. We observed the downregulation of CXCL10 in ncMono of severe COVID-19. Cell-cell communication analysis inferred that the cellular interactions involving ncMono and pDC were reduced in severe COVID-19 compared to moderate COVID-19. Clonal expansions of B cell receptor were most evident in plasmablasts of severe COVID-19. The putative disease genes identified by the GWAS for severe phenotypes showed cell type-specific expressions in monocytes and dendritic cells. Context and cell type-specific expression quantitative trait loci (eQTL) effects of COVID-19-associated risk variants preferably enriched in monocytes of COVID-19 patients (e.g., IFNAR2). In summary, our data linked innate immune cells dysfunction, especially ncMono, with severe COVID-19 and demonstrated the enrichment of host genetic risk in innate immune cells.