SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis.
Cell
; 184(26): 6243-6261.e27, 2021 12 22.
Article
em En
| MEDLINE
| ID: mdl-34914922
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.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fibrose Pulmonar Idiopática
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SARS-CoV-2
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COVID-19
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Macrófagos
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Alemanha