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Eur Respir J2025;66(3)September 1, 2025Journal Article

Multi-omic spatial profiling reveals the unique SARS-CoV-2 lung microenvironment and collagen VI as a predictive biomarker in severe COVID-19.

Éanna Fennell1,2,3,4, Graham S Taylor5,4, Ciara I Leahy1,2,3, Aisling M Ross1,2,3, Gary Reynolds5, Tracey Perry5, Esther Youd6, Jacob Skidmore5, Radwan Ramzi Radwan Darwish1,2,3,7, Kelly J Hunter8, Benjamin E Willcox5,8, Philip Jermann9, Chowdhury Arif Jahangir10, Arman Rahman10, William M Gallagher10, Nadezhda Nikulina11, Bassem Ben Cheikh12, Oliver Braubach13, Aaron T Mayer14, Lawrence S Young15, Dimitris Grammatopoulos15, Sian Faustini16, Alex Richter5,16, Alexander C Dowell5, Tonny Venith17, Onn S Thein18, Dhruv Parekh18, Kylie B R Belchamber18, David R Thickett18, Aaron Scott18, Richard Attanoos19, Lucia Mundo20, Stefano Lazzi20, Lorenzo Leoncini20, Gareth Leopold21, Neil Steven5, Jannie Marie Bülow Sand22, Morten A Karsdal22, Diana Julie Leeming22, Stefan Dojcinov21, Aedin Culhane1,3,23,24, Paul G Murray1,2,3,7,25, Matthew R Pugh26,25
1School of Medicine, University of Limerick, Limerick, Ireland.
2Bernal Institute, University of Limerick, Limerick, Ireland.
3Limerick Digital Cancer Research Centre, Health Research Institute, University of Limerick, Limerick, Ireland.
4É. Fennell and G.S. Taylor contributed equally to this work.
5Department of Immunology and Immunotherapy, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK.
6Forensic Medicine and Science, University of Glasgow, Glasgow, UK.
7School of Medicine, Royal College of Surgeons in Ireland - Medical University of Bahrain, Adliya, Bahrain.
8Birmingham Tissue Analytics, University of Birmingham, Birmingham, UK.
9Department of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
10School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.
11Institute of Lung Health, Justus Liebig University Giessen, Giessen, Germany.
12Akoya Biosciences, Marlborough, MA, USA.
13Bruker Spatial Biology, St Louis, MO, USA.
14Enable Medicine, Menlo Park, CA, USA.
15Warwick Medical School, University of Warwick, Coventry, UK.
16Clinical Immunology Service, University of Birmingham, Birmingham, UK.
17Department of Critical Care and Anaesthesia, Queen Elizabeth Hospital Birmingham, Birmingham, UK.
18Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
19Department of Pathology, University Hospital of Wales, Cardiff, UK.
20Section of Pathology, Department of Medical Biotechnologies, University of Siena, Siena, Italy.
21Department of Cellular Pathology, Swansea Bay University Health Board, Swansea, UK.
22Nordic Bioscience, Herlev, Denmark.
23Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
24Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
25P.G. Murray and M.R. Pugh contributed equally to this work.
26Department of Immunology and Immunotherapy, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK M.Pugh.1@bham.ac.uk.
PubMed PMC DOI PDF

Abstract

BACKGROUND: While coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, few studies have characterised the immune response to COVID-19 in lung tissue. We sought to understand the pathogenic role of microenvironmental interactions and the extracellular matrix in post-mortem COVID-19 lung using an integrative multi-omic approach. METHODS: Post-mortem formalin-fixed paraffin-embe…

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