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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/8108| Single-cell analysis of bronchoalveolar cells in inflammatory and fibrotic post-COVID lung disease | |
| Arjun Nair Puja mehta Blanca Sanz-Magallon Duque de Estrada Emma Denneny Kane Foster Carolin Turner Andreas Mayer Martina Milighetti Manuela Platé Kaylee Worlock Masahiro Yoshida Jeremy Brown Marko Nikolic Benny Chain Mahdad Noursadeghi Rachel Chambers Joanna Porter Gillian Tomlinson | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| https://doi.org/10.1101/2023.03.28.23287759 | |
| https://www.medrxiv.org/content/10.1101/2023.03.28.23287759v1 | |
| Abstract Rationale Persistent pulmonary sequelae are evident in many survivors of acute coronavirus disease 2019 (COVID-19) but the molecular mechanisms responsible are incompletely understood. Post-COVID radiological lung abnormalities comprise two broad categories, organising pneumonia and reticulation, interpreted as indicative of subacute inflammation and fibrosis, respectively. Whether these two patterns represent distinct pathologies, likely to require different treatment strategies is not known. Objectives We sought to identify differences at molecular and cellular level, in the local immunopathology of post-COVID inflammation and fibrosis. Methods We compared single-cell transcriptomic profiles and T cell receptor (TCR) repertoires of bronchoalveolar cells obtained from convalescent individuals with each radiological pattern of post-COVID lung disease (PCLD). Measurements and Main Results Inflammatory and fibrotic PCLD single-cell transcriptomes closely resembled each other across all cell types. However, CD4 central memory T cells (TCM) and CD8 effector memory T cells (TEM) were significantly more abundant in inflammatory PCLD. A greater proportion of CD4 TCM also exhibited clonal expansion in inflammatory PCLD. High levels of clustering of similar TCRs from multiple donors was a striking feature of both PCLD phenotypes, consistent with tissue localised antigen-specific immune responses, but there was no enrichment for known SARS-CoV-2 reactive TCRs. Conclusions There is no evidence that radiographic organising pneumonia and reticulation in PCLD are associated with differential immmunopathological pathways. Inflammatory radiology is characterised by greater bronchoalveolar T cell accumulation. Both groups show evidence of shared antigen-specific T cell responses, but the antigenic target for these T cells remains to be identified. | |
| bioRxiv | |
| 29-03-2023 | |
| Preimpreso | |
| Inglés | |
| Público en general | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Materiales de Consulta y Comunicados Técnicos |
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| Single-cell analysis of bronchoalveolar cells in inflammatory and fibrotic post-COVID lung disease.pdf | 3.59 MB | Adobe PDF | Visualizar/Abrir |