Nat Genet . Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity

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Nat Genet


. 2023 Apr 24.
doi: 10.1038/s41588-023-01375-1. Online ahead of print.
Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity


Ryuya Edahiro ^{# 1 2} , Yuya Shirai ^{# 1 2 3} , Yusuke Takeshima ⁴ , Shuhei Sakakibara ⁵ , Yuta Yamaguchi ^{2 6} , Teruaki Murakami ^{2 6} , Takayoshi Morita ^{2 6} , Yasuhiro Kato ^{2 6} , Yu-Chen Liu ⁷ , Daisuke Motooka ^{7 8 9} , Yoko Naito ⁸ , Ayako Takuwa ⁷ , Fuminori Sugihara ¹⁰ , Kentaro Tanaka ⁸ , James B Wing ^{11 12} , Kyuto Sonehara ^{1 9 13 14} , Yoshihiko Tomofuji ^{1 9 13} ; Japan COVID-19 Task Force; Ho Namkoong ¹⁵ , Hiromu Tanaka ¹⁶ , Ho Lee ¹⁶ , Koichi Fukunaga ¹⁶ , Haruhiko Hirata ² , Yoshito Takeda ² , Daisuke Okuzaki ^{7 8 9 12 17} , Atsushi Kumanogoh ^{18 19 20 21 22} , Yukinori Okada ^{23 24 25 26 27 28}



Collaborators, Affiliations

• PMID: 37095364
• DOI: 10.1038/s41588-023-01375-1

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.