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

Wendisch D, Dietrich O, Mari T, Von Stillfried S, Ibarra IL, Mittermaier M, Mache C, Chua RL, Knoll R, Timm S, Brumhard S, Krammer T, Zauber H, Hiller AL, Pascual-Reguant A, Mothes R, Buelow RD, Schulze J, Leipold AM, Djudjaj S, Erhard F, Geffers R, Pott F, Kazmierski J, Radke J, Pergantis P, Bassler K, Conrad C, Aschenbrenner AC, Sawitzki B, Landthaler M, Wyler E, Horst D, Hippenstiel S, Hocke A, Heppner FL, 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 JL, Radbruch H, Ochs M, Eils R, Müller-Redetzky HC, Hauser AE, Luecken MD, Theis FJ, Conrad C, Wolff T, Boor P, Selbach M, Saliba E, Sander LE (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 184

Pages Range: 6243-6261.e27

Journal Issue: 26

DOI: 10.1016/j.cell.2021.11.033

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.

Involved external institutions

Helmholtz-Zentrum für Infektionsforschung (HZI) Germany (DE) Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich Germany (DE) Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) Robert Koch-Institut (RKI) Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Germany (DE) Julius-Maximilians-Universität Würzburg Germany (DE) Berliner Institut für Gesundheitsforschung (BIH) Germany (DE) Deutsches Rheuma-Forschungszentrum (DRFZ) Germany (DE) Humboldt-Universität zu Berlin Germany (DE) Technische Universität München (TUM) Germany (DE) Universitätsklinikum Würzburg Germany (DE) Deutsches Zentrum für Lungenforschung e.V. (DZL) Germany (DE) Universitätsklinikum Aachen (UKA) Germany (DE)

How to cite

APA:

Wendisch, D., Dietrich, O., Mari, T., Von Stillfried, S., Ibarra, I.L., Mittermaier, M.,... Sander, L.E. (2021). SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis. Cell, 184(26), 6243-6261.e27. https://doi.org/10.1016/j.cell.2021.11.033

MLA:

Wendisch, Daniel, et al. "SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis." Cell 184.26 (2021): 6243-6261.e27.

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