Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19-Reference-Cited by-同舟云学术

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

Published:2022-01-21 Issue:1 Volume:13 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

Unterman Avraham^ORCID,Sumida Tomokazu S.^ORCID,Nouri Nima^ORCID,Yan Xiting,Zhao Amy Y.,Gasque Victor^ORCID,Schupp Jonas C.^ORCID,Asashima Hiromitsu,Liu Yunqing,Cosme Carlos,Deng Wenxuan,Chen Ming,Raredon Micha Sam Brickman^ORCID,Hoehn Kenneth B.^ORCID,Wang Guilin,Wang Zuoheng^ORCID,DeIuliis Giuseppe^ORCID,Ravindra Neal G.^ORCID,Li Ningshan,Castaldi Christopher,Wong Patrick,Fournier John,Bermejo Santos,Sharma Lokesh^ORCID,Casanovas-Massana Arnau^ORCID,Vogels Chantal B. F.^ORCID,Wyllie Anne L.^ORCID,Grubaugh Nathan D.,Melillo Anthony,Meng Hailong,Stein Yan^ORCID,Minasyan Maksym,Mohanty Subhasis,Ruff William E.^ORCID,Cohen Inessa,Raddassi Khadir,Nelson Allison,Shepard Denise,Rainone Michael,Peng Xiaohua,Niklason Laura E.,Ko Albert I.^ORCID,Montgomery Ruth R.^ORCID,Farhadian Shelli F.^ORCID,Iwasaki Akiko^ORCID,Shaw Albert C.,van Dijk David^ORCID,Zhao Hongyu^ORCID,Kleinstein Steven H.^ORCID,Hafler David A.^ORCID,Kaminski Naftali^ORCID,Dela Cruz Charles S.^ORCID,

Abstract

AbstractDysregulated 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.

Funder

Department of Internal Medicine at Yale School of Medicine

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

Link

https://www.nature.com/articles/s41467-021-27716-4.pdf

Reference120 articles.

1. WHO. WHO Coronavirus Disease (COVID-19) Dashboard (2021).

2. Berlin, D. A., Gulick, R. M. & Martinez, F. J. Severe covid-19. N. Engl. J. Med. 383, 2451–2460 (2020).

3. Cummings, M. J. et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet 395, 1763–1770 (2020).