biostudies-literatureWendisch DEuropean Research Council6243-6261.e27https://www.ebi.ac.uk/biostudies/studies/S-EPMC8626230biostudies-literatureUnknown184(26)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 cliniCellSARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis.PMC8626230101001791Radke JEils RZauber HKnoll RTheis FJCochain CMachleidt FSchultze JLPott FThibeault CGoffinet CKazmierski JMuller-Redetzky HDeutsche COVID-19 OMICS Initiative (DeCOI)Mittermaier MOchs MWolff TLandthaler MSelbach MDietrich OIbarra ILLeipold AMSuttorp NHauser AEMari TBoor PDrosten CTimm SSchulze JDjudjaj SGarcia CBrumhard SConrad CChua RLUhrig AWendisch DHerold SKrammer THippenstiel SBaßler KBulow RDHeppner FLKurth FHorst DHocke AWitzenrath MPascual-Reguant AErhard FMache CWyler ELuecken MDElezkurtaj SAschenbrenner ACRadbruch Hvon Stillfried SSawitzki BHiller ALGeffers RSaliba AEPergantis PMothes RSander LEfalseSARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis.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 clini2021-01-01T00:00:00Z2021 Dec2026-05-04T03:18:23.848Z2025-04-19T18:14:44.707ZS-EPMC86262303491492210.1016/j.cell.2021.11.033