Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19

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 stabl...

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Detalles Bibliográficos
Autores principales: Unterman, Avraham, Sumida, Tomokazu S., Nouri, Nima, Yan, Xiting, Zhao, Amy Y., Gasque, Victor, Schupp, Jonas C., Asashima, Hiromitsu, Liu, Yunqing, Cosme, Carlos, Deng, Wenxuan, Chen, Ming, Raredon, Micha Sam Brickman, Hoehn, Kenneth B., Wang, Guilin, Wang, Zuoheng, DeIuliis, Giuseppe, Ravindra, Neal G., Li, Ningshan, Castaldi, Christopher, Wong, Patrick, Fournier, John, Bermejo, Santos, Sharma, Lokesh, Casanovas-Massana, Arnau, Vogels, Chantal B. F., Wyllie, Anne L., Grubaugh, Nathan D., Melillo, Anthony, Meng, Hailong, Stein, Yan, Minasyan, Maksym, Mohanty, Subhasis, Ruff, William E., Cohen, Inessa, Raddassi, Khadir, Niklason, Laura E., Ko, Albert I., Montgomery, Ruth R., Farhadian, Shelli F., Iwasaki, Akiko, Shaw, Albert C., van Dijk, David, Zhao, Hongyu, Kleinstein, Steven H., Hafler, David A., Kaminski, Naftali, Dela Cruz, Charles S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782894/
https://www.ncbi.nlm.nih.gov/pubmed/35064122
http://dx.doi.org/10.1038/s41467-021-27716-4
Descripción
Sumario: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-DR(lo) 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.

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