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

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Item Type:	Article
Title:	SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis
Creators Name:	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. and Sander, L.E.
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 analyzed 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:	CD Antigens, COVID-19, Cell Communication, Cell Surface Receptors, Cohort Studies, Fibroblasts, Gene Expression Regulation, Genetic Transcription, Idiopathic Pulmonary Fibrosis, Macrophages, Mesenchymal Stem Cells, Myelomonocytic Differentiation Antigens, Phenotype, Proteome, Respiratory Distress Syndrome, SARS-CoV-2, X-Ray Computed Tomography
Source:	Cell
ISSN:	0092-8674
Publisher:	Cell Press
Volume:	184
Number:	26
Page Range:	6243-6261
Date:	22 December 2021
Additional Information:	Copyright © 2021 Published by Elsevier Inc.
Official Publication:	https://doi.org/10.1016/j.cell.2021.11.033
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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