Single-cell RNA-seq of bronchoalveolar lavage (BAL) fluid in severe COVID-19 and SARS-CoV-2 stimulated classical blood monocytes

We analyzed pulmonary monocyte and macrophage responses as well as and pulmonary pathology in two cohorts of patients with COVID-19 associated ARDS. Monocyte-derived macrophages accumulated in the lung during ARDS and acquired a profibrotic signature, characterized by high expression of known fibrogenic factors like TGFB1, SPP1 and LGMN. COVID-19 associated macrophages showed highly significant transcriptional similarity with profibrotic macrophage populations identified in idiopathic pulmonary fibrosis (IPF). Notably, overnight exposure to SARS-CoV-2, but not influenza A virus or viral RNA analogues, induced a similar phenotype in human monocytes from healthy volunteers in vitro. Patients with severe COVID-19 associated ARDS showed clear clinical, radiographic and histopathological features of scarring and fibrotic tissue remodeling. In conclusion, SARS-CoV-2 triggers profibrotic macrophage responses, fibroproliferative ARDS, and lung fibrosis

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 4 Publications

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Dataset ID	Description	Technology	Samples
EGAD00001006827	We performed single-cell RNA-sequencing of cells in the bronchoalveolar lavage (BAL) fluid of severe COVID-19. In addition, we performed single-cell RNA-sequencing of SARS-CoV-2 stimulated classical blood monocytes. This study provides detailed insights into the alveolar macrophage response to SARS-CoV-2 infection and reveals a profibrotic macrophage response in severe COVID-19 patients.	Illumina NovaSeq 6000	10

Publications	Citations
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, Bülow 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, Deutsche COVID-19 OMICS Initiative (DeCOI), 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 H, Hauser AE, Luecken MD, Theis FJ, Conrad C, Wolff T, Boor P, Selbach M, Saliba AE, Sander LE. Cell 184: 2021 6243-6261.e27	222
Longitudinal characterization of circulating neutrophils uncovers phenotypes associated with severity in hospitalized COVID-19 patients. LaSalle TJ, Gonye ALK, Freeman SS, Kaplonek P, Gushterova I, Kays KR, Manakongtreecheep K, Tantivit J, Rojas-Lopez M, Russo BC, Sharma N, Thomas MF, Lavin-Parsons KM, Lilly BM, Mckaig BN, Charland NC, Khanna HK, Lodenstein CL, Margolin JD, Blaum EM, Lirofonis PB, Revach OY, Mehta A, Sonny A, Bhattacharyya RP, Parry BA, Goldberg MB, Alter G, Filbin MR, Villani AC, Hacohen N, Sade-Feldman M. Cell Rep Med 3: 2022 100779	28
Altered and allele-specific open chromatin landscape reveals epigenetic and genetic regulators of innate immunity in COVID-19. Zhang B, Zhang Z, Koeken VACM, Kumar S, Aillaud M, Tsay HC, Liu Z, Kraft ARM, Soon CF, Odak I, Bošnjak B, Vlot A, Deutsche COVID-19 OMICS Initiative (DeCOI), Swertz MA, Ohler U, Geffers R, Illig T, Huehn J, Saliba AE, Sander LE, Förster R, Xu CJ, Cornberg M, Schulte LN, Li Y. Cell Genom 3: 2023 100232	8
Th17.1 cell driven sarcoidosis-like inflammation after anti-BCMA CAR T cells in multiple myeloma. Leipold AM, Werner RA, Düll J, Jung P, John M, Stanojkovska E, Zhou X, Hornburger H, Ruckdeschel A, Dietrich O, Imdahl F, Krammer T, Knop S, Rosenwald A, Buck A, Sander LE, Einsele H, Kortüm KM, Saliba AE, Rasche L. Leukemia 37: 2023 650-658	9