Summary

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.

Overall design

Researchers analyzed single-cell transcriptomes and B/T cell receptors from 73 COVID-19 patients and 75 healthy controls, identifying reduced nonclassical monocytes (ncMono) and decreased transitions from classical monocytes in COVID-19. Severe cases showed lower CXCL10 expression and reduced cellular interactions involving ncMono. Clonal B cell expansions were observed in plasmablasts, and genetic risk variants, including at the IFNAR2 locus, were linked to monocyte-specific effects. This study highlights

Contributors

Ryuya Edahiro†, Yuya Shirai†, Atsushi Kumanogoh✉️, Yukinori Okada✉️

Contact

kumanogo@imed3.med.osaka-u.ac.jp (Atsushi Kumanogoh), yokada@sg.med.osaka-u.ac.jp (Yukinori Okada)