Authors
Avraham Unterman, Tomokazu S Sumida, Nima Nouri, Xiting Yan, Amy Y Zhao, Victor Gasque, Jonas C Schupp, Hiromitsu Asashima, Yunqing Liu, Carlos Cosme Jr, Wenxuan Deng, Ming Chen, Micha Sam Brickman Raredon, Kenneth B Hoehn, Guilin Wang, Zuoheng Wang, Giuseppe DeIuliis, Neal G Ravindra, Ningshan Li, Christopher Castaldi, Patrick Wong, John Fournier, Santos Bermejo, Lokesh Sharma, Arnau Casanovas-Massana, Chantal BF Vogels, Anne L Wyllie, Nathan D Grubaugh, Anthony Melillo, Hailong Meng, Yan Stein, Maksym Minasyan, Subhasis Mohanty, William E Ruff, Inessa Cohen, Khadir Raddassi, Yale IMPACT Research Team Nelson Allison 10 Shepard Denise 21 Rainone Michael 1 Peng Xiaohua 1, Laura E Niklason, Albert I Ko, Ruth R Montgomery, Shelli F Farhadian, Akiko Iwasaki, Albert C Shaw, David van Dijk, Hongyu Zhao, Steven H Kleinstein, David A Hafler, Naftali Kaminski, Charles S Dela Cruz
Publication date
2022/1/21
Journal
Nature communications
Volume
13
Issue
1
Pages
440
Publisher
Nature Publishing Group UK
Description
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 S100Ahi/HLA-DRlo classical monocytes and activated LAG-3hi 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 …
Total citations
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