Presentation Information
[OE5-3]Biological and host genetic mechanism of COVID-19 severity identified using large-scale scRNA-seq in Japanese
○Ryuya Edahiro1, Yuya Shirai1, Yusuke Takeshima2, Shuhei Sakakibara2, Yuta Yamaguchi1,2, Teruaki Murakami1,2, Takayoshi Morita1,2, Yasuhiro Kato1,2, Yu-Chen Liu2, Daisuke Motooka2, Ayako Takuwa2, James Wing2, Kyuto Sonehara1,3,4, Japan COVID-19 Task Force, Namkoong Ho5, Hiromu Tanaka5, Ho Lee5, Koichi Fukunaga5, Haruhiko Hirata1, Yoshito Takeda1, Daisuke Okuzaki2, Atsushi Kumanogoh1,2, Yukinori Okada1,2,3,4 (1.Osaka University Graduate School of Medicine, Suita, Japan, 2.Immunology Frontier Research Center, Osaka University, Suita, Japan, 3.Graduate School of Medicine, the University of Tokyo, Tokyo, Japan, 4.RIKEN Center for Integrative Medical Sciences, Yokohama, Japan, 5.Keio University School of Medicine, Tokyo, Japan)
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.