Cited by 528COVID-19 Clinical Research StudiesInterstitial Lung Diseases and Idiopathic Pulmonary FibrosisSARS-CoV-2 and COVID-19 Research

SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis

Open access
Wendisch, Daniel, Dietrich, Oliver, Mari, Tommaso, von Stillfried, Saskia, Ibarra, Ignacio L., Mittermaier, Mirja, Mache, Christin, Chua, Robert Lorenz +54 more·2021·Cell

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.

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Crossref · 10.1016/j.cell.2021.11.033

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  • SARS-CoV-2 triggers a profibrotic response in CD14+CD163+ macrophages that promotes pulmonary fibrosis and acute respiratory distress syndrome.

    “SARS-CoV-2 triggers a profibrotic response in CD14+CD163+ macrophages, which promotes manifest pulmonary fibrosis and acute respiratory distress syndrome (Box 1)”

    From COVID-19 and cellular senescence (2023) · cites this paper as [81]

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Authors
Wendisch, D., Dietrich, O., Mari, T., von Stillfried, S., Ibarra, I. L., Mittermaier, M., Mache, C., Chua, R. L., Knoll, R., Timm, S., Brumhard, S., Krammer, T., Zauber, H., Hiller, A. L., Pascual-Reguant, A., Mothes, R., Bülow, R. D., Schulze, J., Leipold, A. M., Djudjaj, S., Erhard, F., Geffers, R., Pott, F., Kazmierski, J., Radke, J., Pergantis, P., Baßler, K., Conrad, C., Aschenbrenner, A. C., Sawitzki, B., Landthaler, M., Wyler, E., Horst, D., Hippenstiel, S., Hocke, A., Heppner, F. L., Uhrig, A., Garcia, C., Machleidt, F., Herold, S., Elezkurtaj, S., Thibeault, C., Witzenrath, M., Cochain, C., Suttorp, N., Drosten, C., Goffinet, C., Kurth, F., Schultze, J. L., Radbruch, H., Ochs, M., Eils, R., Müller-Redetzky, H., Hauser, A. E., Luecken, M. D., Theis, F. J., Conrad, C., Wolff, T., Boor, P., Selbach, M., Saliba, A.-E., & Sander, L. E.
Affiliations
  • Charité – Universitätsmedizin Berlin (DE)
  • Helmholtz Institute for RNA-based Infection Research (DE)
  • Max Delbrück Center (DE)
  • Helmholtz Munich (DE)
  • Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
  • Robert Koch Institute (DE)
  • Humboldt-Universität zu Berlin (DE)
  • University of Bonn (DE)
  • German Rheumatism Research Centre (DE)
  • Universitätsklinikum Aachen (DE)
  • University of Würzburg (DE)
  • Helmholtz Centre for Infection Research (DE)
  • German Center for Lung Research (DE)
  • German Center for Neurodegenerative Diseases (DE)
  • Universitätsklinikum Gießen und Marburg (DE)
  • Universitätsklinikum Würzburg (DE)
  • German Center for Infection Research (DE)
  • University Medical Center Hamburg-Eppendorf (DE)
Corresponding author
  • Saliba, Antoine-Emmanuel
  • Sander, Leif Erik
Venue
Cell
Publisher
Elsevier BV
Published
2021-12
Volume
184
Issue
26
Pages
6243-6261.e27
ISSN
0092-8674 (ISSN-L)
OpenAlex
W3216618416
Cited by
528
References
149
Citations by year
2026: 52 · 2025: 109 · 2024: 122 · 2023: 146 · 2022: 97 · 2021: 1
FWCI
29.77
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
  • Site cant be reached (submittedVersion, other-oa)
  • DZNE Pub (submittedVersion)
  • RWTH Publications (RWTH Aachen) (submittedVersion, other-oa)
  • HZI (Helmholtz Centre for Infection Research) (submittedVersion, cc-by-nc-nd)
  • RWTH Publications (RWTH Aachen)
Topics
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Keywords
SARS-CoV-2, COVID-19 pandemic, acute respiratory distress syndrome, pulmonary fibrosis, idiopathic pulmonary fibrosis, monocyte-to-macrophage differentiation, lung ultrastructure
MeSH terms
COVID-19, SARS-CoV-2, CD163 Antigen, Cell Communication, Fibroblasts, Gene Expression Regulation, Humans, Macrophages, Phenotype, Receptors, Cell Surface, Respiratory Distress Syndrome, Tomography, X-Ray Computed, Transcription, Genetic, Antigens, Differentiation, Myelomonocytic, Cohort Studies, Antigens, CD, Proteome, Idiopathic Pulmonary Fibrosis, Mesenchymal Stem Cells

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