Frontiers in Immunology (Jun 2024)
Extracellular matrix remodelling pathway in peripheral blood mononuclear cells from severe COVID-19 patients: an explorative study
- Sarah Louise Murphy,
- Sarah Louise Murphy,
- Nora Reka Balzer,
- Nora Reka Balzer,
- Nora Reka Balzer,
- Trine Ranheim,
- Ellen Lund Sagen,
- Ellen Lund Sagen,
- Camilla Huse,
- Camilla Huse,
- Camilla Huse,
- Vigdis Bjerkeli,
- Vigdis Bjerkeli,
- Annika E. Michelsen,
- Annika E. Michelsen,
- Ane-Kristine Finbråten,
- Lars Heggelund,
- Lars Heggelund,
- Anne Ma Dyrhol-Riise,
- Anne Ma Dyrhol-Riise,
- Anders Tveita,
- Anders Tveita,
- Aleksander Rygh Holten,
- Aleksander Rygh Holten,
- Marius Trøseid,
- Marius Trøseid,
- Marius Trøseid,
- Thor Ueland,
- Thor Ueland,
- Thor Ueland,
- Thomas Ulas,
- Thomas Ulas,
- Thomas Ulas,
- Pål Aukrust,
- Pål Aukrust,
- Pål Aukrust,
- Andreas Barratt-Due,
- Andreas Barratt-Due,
- Bente Halvorsen,
- Bente Halvorsen,
- Bente Halvorsen,
- Tuva Børresdatter Dahl
Affiliations
- Sarah Louise Murphy
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Sarah Louise Murphy
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Nora Reka Balzer
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany
- Nora Reka Balzer
- Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
- Nora Reka Balzer
- PRECISE Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany
- Trine Ranheim
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Ellen Lund Sagen
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Ellen Lund Sagen
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Camilla Huse
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Camilla Huse
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Camilla Huse
- Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States
- Vigdis Bjerkeli
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Vigdis Bjerkeli
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Annika E. Michelsen
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Annika E. Michelsen
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Ane-Kristine Finbråten
- Department of Internal Medicine, Lovisenberg Diakonal Hospital, Oslo, Norway
- Lars Heggelund
- Department of Internal Medicine, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway
- Lars Heggelund
- Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway
- Anne Ma Dyrhol-Riise
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Anne Ma Dyrhol-Riise
- 0Department of Infectious Diseases, Oslo University Hospital Ullevål, Oslo, Norway
- Anders Tveita
- 1Department of Internal Medicine, Bærum Hospital, Vestre Viken Hospital Trust, Gjettum, Norway
- Anders Tveita
- 2Division of Laboratory Medicine, Department of Immunology, Oslo University Hospital, Oslo, Norway
- Aleksander Rygh Holten
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Aleksander Rygh Holten
- 3Department of Acute Medicine, Oslo University Hospital, Oslo, Norway
- Marius Trøseid
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Marius Trøseid
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Marius Trøseid
- 4Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Thor Ueland
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Thor Ueland
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Thor Ueland
- 5Thrombosis Research Center (TREC), Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
- Thomas Ulas
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany
- Thomas Ulas
- Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
- Thomas Ulas
- PRECISE Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany
- Pål Aukrust
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Pål Aukrust
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Pål Aukrust
- 4Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Andreas Barratt-Due
- 2Division of Laboratory Medicine, Department of Immunology, Oslo University Hospital, Oslo, Norway
- Andreas Barratt-Due
- 6Department of Anesthesia and Intensive Care Medicine, Oslo University Hospital, Oslo, Norway
- Bente Halvorsen
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Bente Halvorsen
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Bente Halvorsen
- Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States
- Tuva Børresdatter Dahl
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- DOI
- https://doi.org/10.3389/fimmu.2024.1379570
- Journal volume & issue
-
Vol. 15
Abstract
There is a reciprocal relationship between extracellular matrix (ECM) remodelling and inflammation that could be operating in the progression of severe COVID-19. To explore the immune-driven ECM remodelling in COVID-19, we in this explorative study analysed these interactions in hospitalised COVID-19 patients. RNA sequencing and flow analysis were performed on peripheral blood mononuclear cells. Inflammatory mediators in plasma were measured by ELISA and MSD, and clinical information from hospitalised COVID-19 patients (N=15) at admission was included in the analysis. Further, we reanalysed two publicly available datasets: (1) lung tissue RNA-sequencing dataset (N=5) and (2) proteomics dataset from PBCM. ECM remodelling pathways were enriched in PBMC from COVID-19 patients compared to healthy controls. Patients treated at the intensive care unit (ICU) expressed distinct ECM remodelling gene profiles compared to patients in the hospital ward. Several markers were strongly correlated to immune cell subsets, and the dysregulation in the ICU patients was positively associated with plasma levels of inflammatory cytokines and negatively associated with B-cell activating factors. Finally, our analysis of publicly accessible datasets revealed (i) an augmented ECM remodelling signature in inflamed lung tissue compared to non-inflamed tissue and (ii) proteomics analysis of PBMC from severe COVID-19 patients demonstrated an up-regulation in an ECM remodelling pathway. Our results may suggest the presence of an interaction between ECM remodelling, inflammation, and immune cells, potentially initiating or perpetuating pulmonary pathology in severe COVID-19.
Keywords
