Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity
- Resource Type
- Original Paper
- Authors
- Edahiro, Ryuya; Shirai, Yuya; Takeshima, Yusuke; Sakakibara, Shuhei; Yamaguchi, Yuta; Murakami, Teruaki; Morita, Takayoshi; Kato, Yasuhiro; Liu, Yu-Chen; Motooka, Daisuke; Naito, Yoko; Takuwa, Ayako; Sugihara, Fuminori; Tanaka, Kentaro; Wing, James B.; Sonehara, Kyuto; Tomofuji, Yoshihiko; Namkoong, Ho; Tanaka, Hiromu; Lee, Ho; Fukunaga, Koichi; Hirata, Haruhiko; Takeda, Yoshito; Okuzaki, Daisuke; Kumanogoh, Atsushi; Okada, Yukinori
- Source
- Nature Genetics. 55(5):753-767
- Subject
- Language
- English
- ISSN
- 1061-4036
1546-1718
Mechanisms underpinning the dysfunctional immune response in severe acute respiratory syndrome coronavirus 2 infection are elusive. We analyzed single-cell transcriptomes and T and B cell receptors (BCR) of >895,000 peripheral blood mononuclear cells from 73 coronavirus disease 2019 (COVID-19) patients and 75 healthy controls of Japanese ancestry with host genetic data. COVID-19 patients showed a low fraction of nonclassical monocytes (ncMono). We report downregulated cell transitions from classical monocytes to ncMono in COVID-19 with reduced CXCL10 expression in ncMono in severe disease. Cell–cell communication analysis inferred decreased cellular interactions involving ncMono in severe COVID-19. Clonal expansions of BCR were evident in the plasmablasts of patients. Putative disease genes identified by COVID-19 genome-wide association study showed cell type-specific expressions in monocytes and dendritic cells. A COVID-19-associated risk variant at the IFNAR2 locus (rs13050728) had context-specific and monocyte-specific expression quantitative trait loci effects. Our study highlights biological and host genetic involvement of innate immune cells in COVID-19 severity.
Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity.