% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Georg:164035,
author = {Georg, Philipp and Astaburuaga-García, Rosario and
Bonaguro, Lorenzo and Brumhard, Sophia and Michalick, Laura
and Lippert, Lena J and Kostevc, Tomislav and Gäbel,
Christiane and Schneider, Maria and Streitz, Mathias and
Demichev, Vadim and Gemünd, Ioanna Dafni and Barone,
Matthias and Tober-Lau, Pinkus and Helbig, Elisa T and
Hillus, David and Petrov, Lev and Stein, Julia and Dey,
Hannah-Philine and Paclik, Daniela and Iwert, Christina and
Mülleder, Michael and Aulakh, Simran Kaur and Djudjaj,
Sonja and Bülow, Roman D and Mei, Henrik E and Schulz, Axel
R and Thiel, Andreas and Hippenstiel, Stefan and Saliba,
Antoine-Emmanuel and Eils, Roland and Lehmann, Irina and
Mall, Marcus A and Stricker, Sebastian and Röhmel, Jobst
and Corman, Victor and Beule, Dieter and Wyler, Emanuel and
Landthaler, Markus and Obermayer, Benedikt and von
Stillfried, Saskia and Boor, Peter and Demir, Münevver and
Wesselmann, Hans and Suttorp, Norbert and Uhrig, Alexander
and Müller-Redetzky, Holger and Nattermann, Jacob and
Kuebler, Wolfgang M and Meisel, Christian and Ralser, Markus
and Schultze, Joachim L and Aschenbrenner, Anna C and
Thibeault, Charlotte and Kurth, Florian and Sander, Leif E
and Blüthgen, Nils and Sawitzki, Birgit},
collaboration = {Group, PA-COVID-19 Study},
title = {{C}omplement activation induces excessive {T} cell
cytotoxicity in severe {COVID}-19.},
journal = {Cell},
volume = {185},
number = {3},
issn = {0092-8674},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DZNE-2022-00698},
pages = {493 - 512.e25},
year = {2022},
abstract = {Severe COVID-19 is linked to both dysfunctional immune
response and unrestrained immunopathology, and it remains
unclear whether T cells contribute to disease pathology.
Here, we combined single-cell transcriptomics and
single-cell proteomics with mechanistic studies to assess
pathogenic T cell functions and inducing signals. We
identified highly activated CD16+ T cells with increased
cytotoxic functions in severe COVID-19. CD16 expression
enabled immune-complex-mediated, T cell receptor-independent
degranulation and cytotoxicity not found in other diseases.
CD16+ T cells from COVID-19 patients promoted microvascular
endothelial cell injury and release of neutrophil and
monocyte chemoattractants. CD16+ T cell clones persisted
beyond acute disease maintaining their cytotoxic phenotype.
Increased generation of C3a in severe COVID-19 induced
activated CD16+ cytotoxic T cells. Proportions of activated
CD16+ T cells and plasma levels of complement proteins
upstream of C3a were associated with fatal outcome of
COVID-19, supporting a pathological role of exacerbated
cytotoxicity and complement activation in COVID-19.},
keywords = {Adult / Aged / Aged, 80 and over / COVID-19: immunology /
COVID-19: pathology / COVID-19: virology / Chemotactic
Factors: metabolism / Complement Activation / Cytotoxicity,
Immunologic / Endothelial Cells: virology / Female / Humans
/ Lymphocyte Activation / Male / Microvessels: virology /
Middle Aged / Monocytes: metabolism / Neutrophils:
metabolism / Proteome / Receptors, IgG: metabolism /
SARS-CoV-2: immunology / Single-Cell Analysis /
T-Lymphocytes, Cytotoxic: immunology / Transcriptome / Young
Adult / COVID-19 (Other) / T cells (Other) / complement
(Other) / cytotoxicity (Other) / immunopathology (Other) /
Chemotactic Factors (NLM Chemicals) / Proteome (NLM
Chemicals) / Receptors, IgG (NLM Chemicals)},
cin = {Schultze - PRECISE / $R\&D$ PRECISE},
ddc = {610},
cid = {I:(DE-2719)1013031 / I:(DE-2719)5000031},
pnm = {354 - Disease Prevention and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-354},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35032429},
pmc = {pmc:PMC8712270},
doi = {10.1016/j.cell.2021.12.040},
url = {https://pub.dzne.de/record/164035},
}