1. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
- Author
-
Avraham Unterman, Tomokazu S. Sumida, Nima Nouri, Xiting Yan, Amy Y. Zhao, Victor Gasque, Jonas C. Schupp, Hiromitsu Asashima, Yunqing Liu, Carlos Cosme, 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 B. F. Vogels, Anne L. Wyllie, Nathan D. Grubaugh, Anthony Melillo, Hailong Meng, Yan Stein, Maksym Minasyan, Subhasis Mohanty, William E. Ruff, Inessa Cohen, Khadir Raddassi, The Yale IMPACT Research Team, 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, and Charles S. Dela Cruz
- Subjects
CD4-Positive T-Lymphocytes ,Male ,Science ,Receptors, Antigen, T-Cell ,General Physics and Astronomy ,Systems analysis ,Receptors, Antigen, B-Cell ,Adaptive Immunity ,CD8-Positive T-Lymphocytes ,Antibodies, Monoclonal, Humanized ,General Biochemistry, Genetics and Molecular Biology ,Article ,Humans ,RNA-Seq ,Cells, Cultured ,Aged ,Multidisciplinary ,SARS-CoV-2 ,Gene Expression Profiling ,COVID-19 ,General Chemistry ,biochemical phenomena, metabolism, and nutrition ,Cellular immunity ,Immunity, Innate ,COVID-19 Drug Treatment ,Gene Expression Regulation ,Viral infection ,bacteria ,Female ,Single-Cell Analysis - Abstract
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, 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.
- Published
- 2022