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

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, Laura E. Niklason, Albert I. Ko, Ruth R. Montgomery, Shelli F. Farhadian, Akiko Iwasaki, Albert C. Shaw, David Dijk, Hongyu Zhao, Steven H. Kleinstein, David A. Hafler, Naftali Kaminski and Charles S. Cruz
Additional contact information
Avraham Unterman: School of Medicine, Yale University
Tomokazu S. Sumida: School of Medicine, Yale University
Nima Nouri: Yale School of Medicine
Xiting Yan: School of Medicine, Yale University
Amy Y. Zhao: School of Medicine, Yale University
Victor Gasque: Yale University
Jonas C. Schupp: School of Medicine, Yale University
Hiromitsu Asashima: School of Medicine, Yale University
Yunqing Liu: Yale School of Public Health, Yale University
Carlos Cosme: School of Medicine, Yale University
Wenxuan Deng: Yale School of Public Health, Yale University
Ming Chen: Yale School of Public Health, Yale University
Micha Sam Brickman Raredon: School of Medicine, Yale University
Kenneth B. Hoehn: Yale School of Medicine
Guilin Wang: Yale School of Medicine
Zuoheng Wang: Yale School of Public Health, Yale University
Giuseppe DeIuliis: School of Medicine, Yale University
Neal G. Ravindra: Yale University
Ningshan Li: Yale School of Public Health, Yale University
Christopher Castaldi: Yale School of Medicine
Patrick Wong: School of Medicine, Yale University
John Fournier: Yale University
Santos Bermejo: School of Medicine, Yale University
Lokesh Sharma: School of Medicine, Yale University
Arnau Casanovas-Massana: Yale School of Public Health
Chantal B. F. Vogels: Yale School of Public Health
Anne L. Wyllie: Yale School of Public Health
Nathan D. Grubaugh: Yale School of Public Health
Anthony Melillo: Yale School of Medicine
Hailong Meng: Yale School of Medicine
Yan Stein: Tel Aviv Sourasky Medical Center, Tel Aviv University
Maksym Minasyan: School of Medicine, Yale University
Subhasis Mohanty: Yale School of Medicine, Yale University
William E. Ruff: School of Medicine, Yale University
Inessa Cohen: School of Medicine, Yale University
Khadir Raddassi: School of Medicine, Yale University
Laura E. Niklason: Yale University
Albert I. Ko: Yale School of Public Health
Ruth R. Montgomery: Yale School of Medicine
Shelli F. Farhadian: School of Medicine, Yale University
Akiko Iwasaki: School of Medicine, Yale University
Albert C. Shaw: Yale School of Medicine, Yale University
David Dijk: Yale University
Hongyu Zhao: Yale School of Public Health, Yale University
Steven H. Kleinstein: School of Medicine, Yale University
David A. Hafler: School of Medicine, Yale University
Naftali Kaminski: School of Medicine, Yale University
Charles S. Cruz: School of Medicine, Yale University

Nature Communications, 2022, vol. 13, issue 1, 1-23

Abstract: 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.

Date: 2022
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Citations: View citations in EconPapers (5)

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DOI: 10.1038/s41467-021-27716-4

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