期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-27716-4
关键词
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资金
- National Institutes of Health [P01 AI39671, P01 AI073748, 1R01 HL141852-01A1, U01 HL145567, RO1 HL126094, R01 AI104739, 5R01 AI121207, U19 AI089992]
- National Library of Medicine award [5T15LM007056]
- VA Merit [BX004661]
- Department of Defense grant [PR181442, R21 LM012884, F30 HL143906]
- NIH [R35GM143072]
- Merck Investigator Studies Program (SFF)
- Ludwig Family Foundation
- Beatrice Kleinberg Neuwirth Fund
- Yale School of Public Health
- Department of Internal Medicine at Yale School of Medicine
Using multi-omics single-cell analysis, this study reveals the immune abnormalities associated with progressive COVID-19, including S100A(hi)/HLA-DRlo classical monocytes and activated LAG-3(hi) T cells. It also finds a correlation between T cell receptor repertoire and B cell somatic hypermutation frequency with disease progression.
Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, the immune signatures associated with immunopathology are poorly understood. Here we use multi-omics single-cell analysis to probe the dynamic immune responses in hospitalized patients with stable or progressive course of COVID-19, explore V(D)J repertoires, and assess the cellular effects of tocilizumab. Coordinated profiling of gene expression and cell lineage protein markers shows that S100A(hi)/HLA-DRlo classical monocytes and activated LAG-3(hi) T cells are hallmarks of progressive disease and highlights the abnormal MHC-II/LAG-3 interaction on myeloid and T cells, respectively. We also find skewed T cell receptor repertories in expanded effector CD8(+) clones, unmutated IGHG(+) B cell clones, and mutated B cell clones with stable somatic hypermutation frequency over time. In conclusion, our in-depth immune profiling reveals dyssynchrony of the innate and adaptive immune interaction in progressive COVID-19. SARS-CoV-2 infection can lead to progressive pathology in patients with COVID-19, but information for this disease progression is sparse. Here the authors use multi-omics approach to profile the immune responses of patients, assessing immune repertoire and effects of tocilizumab treatments, to find a dyssynchrony between innate and adaptive immunity in progressive COVID-19.
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