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

被引：116

作者：

Unterman, Avraham ^{[1
,2
]}

Sumida, Tomokazu S. ^{[3
,4
]}

Nouri, Nima ^{[5
,6
,7
]}

Yan, Xiting ^{[1
,8
]}

Zhao, Amy Y. ^{[1
,9
,10
]}

Gasque, Victor ^{[11
,12
]}

Schupp, Jonas C. ^{[1
,13
,14
]}

Asashima, Hiromitsu ^{[3
,4
]}

Liu, Yunqing ^{[8
]}

Cosme, Carlos ^{[1
]}

Deng, Wenxuan ^{[8
]}

Chen, Ming ^{[8
]}

Raredon, Micha Sam Brickman ^{[1
,15
,16
]}

Hoehn, Kenneth B. ^{[5
]}

Wang, Guilin ^{[17
]}

Wang, Zuoheng ^{[8
]}

DeIuliis, Giuseppe ^{[1
]}

Ravindra, Neal G. ^{[11
,12
]}

Li, Ningshan ^{[8
,18
]}

Castaldi, Christopher ^{[19
]}

Wong, Patrick ^{[4
]}

Fournier, John ^{[20
]}

Bermejo, Santos ^{[1
]}

Sharma, Lokesh ^{[1
]}

Casanovas-Massana, Arnau ^{[21
]}

Vogels, Chantal B. F. ^{[21
]}

Wyllie, Anne L. ^{[21
]}

Grubaugh, Nathan D. ^{[21
]}

Melillo, Anthony ^{[5
]}

Meng, Hailong ^{[5
]}

Stein, Yan ^{[2
]}

Minasyan, Maksym ^{[1
]}

Mohanty, Subhasis ^{[22
]}

Ruff, William E. ^{[3
,4
]}

Cohen, Inessa ^{[3
,4
]}

Raddassi, Khadir ^{[3
,4
]}

Niklason, Laura E. ^{[15
,23
]}

Ko, Albert, I ^{[21
]}

Montgomery, Ruth R. ^{[10
]}

Farhadian, Shelli F. ^{[3
,22
]}

Iwasaki, Akiko ^{[4
,24
]}

Shaw, Albert C. ^{[22
]}

van Dijk, David ^{[11
,12
]}

Zhao, Hongyu ^{[8
,9
,18
,25
]}

Kleinstein, Steven H. ^{[4
,5
,25
]}

Hafler, David A. ^{[3
,4
]}

Kaminski, Naftali ^{[1
]}

Dela Cruz, Charles S. ^{[1
,26
]}

机构：

[1] Yale Univ, Sch Med, Dept Internal Med, Sect Pulm Crit Care & Sleep Med, New Haven, CT 06510 USA

[2] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Pulm Inst, Tel Aviv, Israel

[3] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA

[4] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA

[5] Yale Sch Med, Dept Pathol, New Haven, CT USA

[6] Yale Sch Med, Ctr Med Informat, New Haven, CT USA

[7] Jackson Lab Genom Med, Farmington, CT USA

[8] Yale Univ, Yale Sch Publ Hlth, Dept Biostat, New Haven, CT USA

[9] Yale Sch Med, Dept Genet, New Haven, CT USA

[10] Yale Sch Med, Dept Internal Med, New Haven, CT USA

[11] Yale Univ, Dept Comp Sci, POB 2158, New Haven, CT 06520 USA

[12] Yale Sch Med, Cardiovasc Res Ctr, Dept Internal Med, Sect Cardiovasc Med, New Haven, CT USA

[13] Hannover Med Sch, Dept Resp Med, Hannover, Germany

[14] German Lung Res Ctr DZL, Biomed Res End Stage & Obstruct Lung Dis Hannover, Hannover, Germany

[15] Yale Univ, Dept Biomed Engn, New Haven, CT USA

[16] Yale Sch Med, Med Scientist Training Program, New Haven, CT USA

[17] Yale Sch Med, Yale Ctr Genome Anal, Dept Mol Biophys & Biochem, Keck Biotechnol Resource Lab, New Haven, CT USA

[18] Shanghai Jiao Tong Univ, SJTU Yale Joint Ctr Biostat & Data Sci, Sch Life Sci & Biotechnol, Dept Bioinformat & Biostat, Shanghai, Peoples R China

[19] Yale Sch Med, Yale Ctr Genome Anal, New Haven, CT USA

[20] Yale Univ, Sch Med, New Haven, CT USA

[21] Yale Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT USA

[22] Yale Univ, Yale Sch Med, Dept Internal Med, Sect Infect Dis, New Haven, CT USA

[23] Yale Univ, Dept Anesthesiol, New Haven, CT USA

[24] Howard Hughes Med Inst, Chevy Chase, MD USA

[25] Yale Univ, Interdept Program Computat Biol & Bioinformat, New Haven, CT USA

[26] West Haven Vet Affair Med Ctr, West Haven, CT USA

来源：

NATURE COMMUNICATIONS | 2022年 / 13卷 / 01期

基金：

美国国家卫生研究院;

关键词：

CD8(+) T-CELLS; SET ENRICHMENT ANALYSIS; SUPPRESSOR-CELLS; INFECTION; SIGNATURES; INFLAMMATION; ACTIVATION; RESPONSES; SEVERITY; DYNAMICS;

D O I：

10.1038/s41467-021-27716-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-DRlo 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. 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.

引用

页数：23

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