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Series GSE228236 Query DataSets for GSE228236
Status Public on Jun 05, 2024
Title Single-cell analysis of bronchoalveolar cells in inflammatory and fibrotic post-COVID lung disease
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary 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 post-COVID lung disease 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.
Overall design Comparison of bronchoalveolar cells from individuals with either inflammatory or fibrotic post-COVID lung disease.
Contributor(s) Mehta P, Sanz-Magallon Duque de Estrada B, Denneny EK, Foster K, Worlock KB, Yoshida M, Tomlinson GS
Citation(s) 38827740
Submission date Mar 27, 2023
Last update date Jun 06, 2024
Contact name Gillian S Tomlinson
Organization name University College London
Department Infection and Immunity
Street address Gower Street
City London
ZIP/Postal code WC1E 6BT
Country United Kingdom
Platforms (2)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (18)
GSM7117552 PCLD1, scRNAseq
GSM7117553 PCLD3, scRNAseq
GSM7117554 PCLD4, scRNAseq
BioProject PRJNA949104

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Supplementary file Size Download File type/resource
GSE228236_RAW.tar 185.6 Mb (http)(custom) TAR (of CSV, H5)
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Raw data are available in SRA
Processed data provided as supplementary file

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