TY - JOUR
T1 - Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
AU - The Yale IMPACT Research Team
AU - Unterman, Avraham
AU - Sumida, Tomokazu S.
AU - Nouri, Nima
AU - Yan, Xiting
AU - Zhao, Amy Y.
AU - Gasque, Victor
AU - Schupp, Jonas C.
AU - Asashima, Hiromitsu
AU - Liu, Yunqing
AU - Cosme, Carlos
AU - Deng, Wenxuan
AU - Chen, Ming
AU - Raredon, Micha Sam Brickman
AU - Hoehn, Kenneth B.
AU - Wang, Guilin
AU - Wang, Zuoheng
AU - DeIuliis, Giuseppe
AU - Ravindra, Neal G.
AU - Li, Ningshan
AU - Castaldi, Christopher
AU - Wong, Patrick
AU - Fournier, John
AU - Bermejo, Santos
AU - Sharma, Lokesh
AU - Casanovas-Massana, Arnau
AU - Vogels, Chantal B.F.
AU - Wyllie, Anne L.
AU - Grubaugh, Nathan D.
AU - Melillo, Anthony
AU - Meng, Hailong
AU - Stein, Yan
AU - Minasyan, Maksym
AU - Mohanty, Subhasis
AU - Ruff, William E.
AU - Cohen, Inessa
AU - Raddassi, Khadir
AU - Nelson, Allison
AU - Shepard, Denise
AU - Rainone, Michael
AU - Peng, Xiaohua
AU - Niklason, Laura E.
AU - Ko, Albert I.
AU - Montgomery, Ruth R.
AU - Farhadian, Shelli F.
AU - Iwasaki, Akiko
AU - Shaw, Albert C.
AU - van Dijk, David
AU - Zhao, Hongyu
AU - Kleinstein, Steven H.
AU - Hafler, David A.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85123489038&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-27716-4
DO - 10.1038/s41467-021-27716-4
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 35064122
AN - SCOPUS:85123489038
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 440
ER -
