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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...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2022
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| Materias: | |
| 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 |
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| author | 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. |
| author_facet | 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. |
| author_sort | Unterman, Avraham |
| collection | PubMed |
| 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 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. |
| format | Online Article Text |
| id | pubmed-8782894 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-87828942022-02-04 Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19 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. Nat Commun Article 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. Nature Publishing Group UK 2022-01-21 /pmc/articles/PMC8782894/ /pubmed/35064122 http://dx.doi.org/10.1038/s41467-021-27716-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article 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. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19 |
| title | Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19 |
| title_full | Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19 |
| title_fullStr | Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19 |
| title_full_unstemmed | Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19 |
| title_short | Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19 |
| title_sort | single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive covid-19 |
| topic | Article |
| url | 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 |
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