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Distinct lung cell signatures define the temporal evolution of diffuse alveolar damage in fatal COVID-19

Luke Milross Orcid Logo, Bethany Hunter, David McDonald, George Merces, Amanda Thomson, Catharien M.U. Hilkens, John Wills, Paul Rees Orcid Logo, Kasim Jiwa, Nigel Cooper, Joaquim Majo, Helen Ashwin, Christopher J.A. Duncan, Paul M. Kaye, Omer Ali Bayraktar, Andrew Filby, Andrew J. Fisher

eBioMedicine, Volume: 99, Start page: 104945

Swansea University Author: Paul Rees Orcid Logo

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Abstract

BackgroundLung damage in severe COVID-19 is highly heterogeneous however studies with dedicated spatial distinction of discrete temporal phases of diffuse alveolar damage (DAD) and alternate lung injury patterns are lacking. Existing studies have also not accounted for progressive airspace obliterat...

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Published in: eBioMedicine
ISSN: 2352-3964
Published: Elsevier BV 2024
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa68201
Abstract: BackgroundLung damage in severe COVID-19 is highly heterogeneous however studies with dedicated spatial distinction of discrete temporal phases of diffuse alveolar damage (DAD) and alternate lung injury patterns are lacking. Existing studies have also not accounted for progressive airspace obliteration in cellularity estimates. We used an imaging mass cytometry (IMC) analysis with an airspace correction step to more accurately identify the cellular immune response that underpins the heterogeneity of severe COVID-19 lung disease.MethodsLung tissue was obtained at post-mortem from severe COVID-19 deaths. Pathologist-selected regions of interest (ROIs) were chosen by light microscopy representing the patho-evolutionary spectrum of DAD and alternate disease phenotypes were selected for comparison. Architecturally normal SARS-CoV-2-positive lung tissue and tissue from SARS-CoV-2-negative donors served as controls. ROIs were stained for 40 cellular protein markers and ablated using IMC before segmented cells were classified. Cell populations corrected by ROI airspace and their spatial relationships were compared across lung injury patterns.FindingsForty patients (32M:8F, age: 22–98), 345 ROIs and >900k single cells were analysed. DAD progression was marked by airspace obliteration and significant increases in mononuclear phagocytes (MnPs), T and B lymphocytes and significant decreases in alveolar epithelial and endothelial cells. Neutrophil populations proved stable overall although several interferon-responding subsets demonstrated expansion. Spatial analysis revealed immune cell interactions occur prior to microscopically appreciable tissue injury.InterpretationThe immunopathogenesis of severe DAD in COVID-19 lung disease is characterised by sustained increases in MnPs and lymphocytes with key interactions occurring even prior to lung injury is established.
Keywords: COVID-19; Post-mortem lung tissue; Diffuse alveolar damage; Immunopathology; Imaging mass cytometry
College: Faculty of Science and Engineering
Funders: This work was partly funded by UKRI/Medical Research Council through the UK Coronavirus Immunology Consortium (UK-CIC) as well as the Barbour Foundation.
Start Page: 104945