TY  - JOUR
AU  - Wendisch, Daniel
AU  - Dietrich, Oliver
AU  - Mari, Tommaso
AU  - von Stillfried, Saskia
AU  - Ibarra, Ignacio L
AU  - Mittermaier, Mirja
AU  - Mache, Christin
AU  - Chua, Robert Lorenz
AU  - Knoll, Rainer
AU  - Timm, Sara
AU  - Brumhard, Sophia
AU  - Krammer, Tobias
AU  - Zauber, Henrik
AU  - Hiller, Anna Luisa
AU  - Pascual-Reguant, Anna
AU  - Mothes, Ronja
AU  - Bülow, Roman David
AU  - Schulze, Jessica
AU  - Leipold, Alexander M
AU  - Djudjaj, Sonja
AU  - Erhard, Florian
AU  - Geffers, Robert
AU  - Pott, Fabian
AU  - Kazmierski, Julia
AU  - Radke, Josefine
AU  - Pergantis, Panagiotis
AU  - Baßler, Kevin
AU  - Conrad, Claudia
AU  - Aschenbrenner, Anna C
AU  - Sawitzki, Birgit
AU  - Landthaler, Markus
AU  - Wyler, Emanuel
AU  - Horst, David
AU  - Hippenstiel, Stefan
AU  - Hocke, Andreas
AU  - Heppner, Frank L
AU  - Uhrig, Alexander
AU  - Garcia, Carmen
AU  - Machleidt, Felix
AU  - Herold, Susanne
AU  - Elezkurtaj, Sefer
AU  - Thibeault, Charlotte
AU  - Witzenrath, Martin
AU  - Cochain, Clément
AU  - Suttorp, Norbert
AU  - Drosten, Christian
AU  - Goffinet, Christine
AU  - Kurth, Florian
AU  - Schultze, Joachim L
AU  - Radbruch, Helena
AU  - Ochs, Matthias
AU  - Eils, Roland
AU  - Müller-Redetzky, Holger
AU  - Hauser, Anja E
AU  - Luecken, Malte D
AU  - Theis, Fabian J
AU  - Conrad, Christian
AU  - Wolff, Thorsten
AU  - Boor, Peter
AU  - Selbach, Matthias
AU  - Saliba, Antoine-Emmanuel
AU  - Sander, Leif Erik
TI  - SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis.
JO  - Cell
VL  - 184
IS  - 26
SN  - 0092-8674
CY  - New York, NY
PB  - Elsevier
M1  - DZNE-2022-00102
SP  - 6243 - 6261.e27
PY  - 2021
AB  - 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.
KW  - Antigens, CD: metabolism
KW  - Antigens, Differentiation, Myelomonocytic: metabolism
KW  - COVID-19: diagnostic imaging
KW  - COVID-19: pathology
KW  - COVID-19: virology
KW  - Cell Communication
KW  - Cohort Studies
KW  - Fibroblasts: pathology
KW  - Gene Expression Regulation
KW  - Humans
KW  - Idiopathic Pulmonary Fibrosis: diagnostic imaging
KW  - Idiopathic Pulmonary Fibrosis: genetics
KW  - Idiopathic Pulmonary Fibrosis: pathology
KW  - Idiopathic Pulmonary Fibrosis: virology
KW  - Macrophages: pathology
KW  - Macrophages: virology
KW  - Mesenchymal Stem Cells: pathology
KW  - Phenotype
KW  - Proteome: metabolism
KW  - Receptors, Cell Surface: metabolism
KW  - Respiratory Distress Syndrome: diagnostic imaging
KW  - Respiratory Distress Syndrome: pathology
KW  - Respiratory Distress Syndrome: virology
KW  - SARS-CoV-2: physiology
KW  - Tomography, X-Ray Computed
KW  - Transcription, Genetic
KW  - ARDS (Other)
KW  - COVID-19 (Other)
KW  - IPF (Other)
KW  - SARS-CoV-2 (Other)
KW  - fibrosis (Other)
KW  - lung (Other)
KW  - macrophages (Other)
KW  - monocytes (Other)
KW  - proteomics (Other)
KW  - pulmonary fibrosis (Other)
KW  - single-cell transcriptomics (Other)
KW  - Antigens, CD (NLM Chemicals)
KW  - Antigens, Differentiation, Myelomonocytic (NLM Chemicals)
KW  - CD163 antigen (NLM Chemicals)
KW  - Proteome (NLM Chemicals)
KW  - Receptors, Cell Surface (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:34914922
C2  - pmc:PMC8626230
DO  - DOI:10.1016/j.cell.2021.11.033
UR  - https://pub.dzne.de/record/163322
ER  -