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@ARTICLE{Wendisch:163322,
author = {Wendisch, Daniel and Dietrich, Oliver and Mari, Tommaso and
von Stillfried, Saskia and Ibarra, Ignacio L and
Mittermaier, Mirja and Mache, Christin and Chua, Robert
Lorenz and Knoll, Rainer and Timm, Sara and Brumhard, Sophia
and Krammer, Tobias and Zauber, Henrik and Hiller, Anna
Luisa and Pascual-Reguant, Anna and Mothes, Ronja and
Bülow, Roman David and Schulze, Jessica and Leipold,
Alexander M and Djudjaj, Sonja and Erhard, Florian and
Geffers, Robert and Pott, Fabian and Kazmierski, Julia and
Radke, Josefine and Pergantis, Panagiotis and Baßler, Kevin
and Conrad, Claudia and Aschenbrenner, Anna C and Sawitzki,
Birgit and Landthaler, Markus and Wyler, Emanuel and Horst,
David and Hippenstiel, Stefan and Hocke, Andreas and
Heppner, Frank L and Uhrig, Alexander and Garcia, Carmen and
Machleidt, Felix and Herold, Susanne and Elezkurtaj, Sefer
and Thibeault, Charlotte and Witzenrath, Martin and Cochain,
Clément and Suttorp, Norbert and Drosten, Christian and
Goffinet, Christine and Kurth, Florian and Schultze, Joachim
L and Radbruch, Helena and Ochs, Matthias and Eils, Roland
and Müller-Redetzky, Holger and Hauser, Anja E and Luecken,
Malte D and Theis, Fabian J and Conrad, Christian and Wolff,
Thorsten and Boor, Peter and Selbach, Matthias and Saliba,
Antoine-Emmanuel and Sander, Leif Erik},
collaboration = {Initiative, Deutsche COVID-19 OMICS},
title = {{SARS}-{C}o{V}-2 infection triggers profibrotic macrophage
responses and lung fibrosis.},
journal = {Cell},
volume = {184},
number = {26},
issn = {0092-8674},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DZNE-2022-00102},
pages = {6243 - 6261.e27},
year = {2021},
abstract = {COVID-19-induced 'acute respiratory distress syndrome'
(ARDS) is associated with prolonged respiratory failure and
high mortality, but the mechanistic basis of lung injury
remains incompletely understood. Here, we analyze pulmonary
immune responses and lung pathology in two cohorts of
patients with COVID-19 ARDS using functional single-cell
genomics, immunohistology, and electron microscopy. We
describe an accumulation of CD163-expressing
monocyte-derived macrophages that acquired a profibrotic
transcriptional phenotype during COVID-19 ARDS. Gene set
enrichment and computational data integration revealed a
significant similarity between COVID-19-associated
macrophages and profibrotic macrophage populations
identified in idiopathic pulmonary fibrosis. COVID-19 ARDS
was associated with clinical, radiographic,
histopathological, and ultrastructural hallmarks of
pulmonary fibrosis. Exposure of human monocytes to
SARS-CoV-2, but not influenza A virus or viral RNA analogs,
was sufficient to induce a similar profibrotic phenotype in
vitro. In conclusion, we demonstrate that SARS-CoV-2
triggers profibrotic macrophage responses and pronounced
fibroproliferative ARDS.},
keywords = {Antigens, CD: metabolism / Antigens, Differentiation,
Myelomonocytic: metabolism / COVID-19: diagnostic imaging /
COVID-19: pathology / COVID-19: virology / Cell
Communication / Cohort Studies / Fibroblasts: pathology /
Gene Expression Regulation / Humans / Idiopathic Pulmonary
Fibrosis: diagnostic imaging / Idiopathic Pulmonary
Fibrosis: genetics / Idiopathic Pulmonary Fibrosis:
pathology / Idiopathic Pulmonary Fibrosis: virology /
Macrophages: pathology / Macrophages: virology / Mesenchymal
Stem Cells: pathology / Phenotype / Proteome: metabolism /
Receptors, Cell Surface: metabolism / Respiratory Distress
Syndrome: diagnostic imaging / Respiratory Distress
Syndrome: pathology / Respiratory Distress Syndrome:
virology / SARS-CoV-2: physiology / Tomography, X-Ray
Computed / Transcription, Genetic / ARDS (Other) / COVID-19
(Other) / IPF (Other) / SARS-CoV-2 (Other) / fibrosis
(Other) / lung (Other) / macrophages (Other) / monocytes
(Other) / proteomics (Other) / pulmonary fibrosis (Other) /
single-cell transcriptomics (Other) / Antigens, CD (NLM
Chemicals) / Antigens, Differentiation, Myelomonocytic (NLM
Chemicals) / CD163 antigen (NLM Chemicals) / Proteome (NLM
Chemicals) / Receptors, Cell Surface (NLM Chemicals)},
cin = {Schultze - PRECISE / $R\&D$ PRECISE / AG Heppner},
ddc = {610},
cid = {I:(DE-2719)1013031 / I:(DE-2719)5000031 /
I:(DE-2719)1810007},
pnm = {354 - Disease Prevention and Healthy Aging (POF4-354) / 353
- Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-354 / G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34914922},
pmc = {pmc:PMC8626230},
doi = {10.1016/j.cell.2021.11.033},
url = {https://pub.dzne.de/record/163322},
}