Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity.
Abstract
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.
| Authors: | Edahiro R, Shirai Y, Takeshima Y, Sakakibara S, Yamaguchi Y, Murakami T, Morita T, Kato Y, Liu YC, Motooka D, Naito Y, Takuwa A, Sugihara F, Tanaka K, Wing JB, Sonehara K, Tomofuji Y, Japan COVID-19 Task Force, Namkoong H, Tanaka H, Lee H, Fukunaga K, Hir |
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| Journal: | Nat Genet;2023May; 55 (5) 753. doi:10.1038/s41588-023-01375-1 |
| Year: | 2023 |
| PubMed: | PMID: 37095364 (Go to PubMed) |