Extracellular matrix turnover in severe COVID-19 is reduced by corticosteroids
Abstract Background Severe and critical COVID-19 is characterized by pulmonary viral infection with SARS-CoV-2 resulting in local and systemic inflammation. Dexamethasone (DEX) has been shown to improve outcomes in critically ill patients; however, its effect on tissue remodeling, particularly colla...
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BMC
2025-01-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-025-03098-9 |
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| author | Janesh Pillay Antine W. Flikweert Matijs van Meurs Marco J. Grootenboers Simone van der Sar-van der Brugge Peter H. J. van der Voort Morten A. Karsdal Jannie M. B. Sand Diana J. Leeming Janette K. Burgess Jill Moser |
| author_facet | Janesh Pillay Antine W. Flikweert Matijs van Meurs Marco J. Grootenboers Simone van der Sar-van der Brugge Peter H. J. van der Voort Morten A. Karsdal Jannie M. B. Sand Diana J. Leeming Janette K. Burgess Jill Moser |
| author_sort | Janesh Pillay |
| collection | DOAJ |
| description | Abstract Background Severe and critical COVID-19 is characterized by pulmonary viral infection with SARS-CoV-2 resulting in local and systemic inflammation. Dexamethasone (DEX) has been shown to improve outcomes in critically ill patients; however, its effect on tissue remodeling, particularly collagen turnover, remains unclear. This study investigated the association between circulating extracellular matrix (ECM) remodeling neo-epitopes and COVID-19 severity, their relationship with mortality, and the effect of DEX on these markers. Methods We conducted a multi-center prospective cohort study involving 226 COVID-19 patients: 157 with severe disease admitted to the ward and 69 with critical disease admitted to the ICU. Plasma samples were collected at ICU admission and at discharge or death. Circulating collagen degradation (C3M, C4Ma3, and C6M) and synthesis (PRO-C3, PRO-C4, and PRO-C6) neo-epitopes were measured. Longitudinal analysis of ECM neo-epitope changes during ICU stay and their association with mortality was performed, along with an evaluation of the impact of DEX treatment on these markers. Results Critically ill patients exhibited higher levels of collagen degradation (reflecting inflammatory driven ECM destruction) (C3M, C6M) and collagen synthesis (strongly related to fibroblast activity) (PRO-C3, PRO-C6) neo-epitopes than severe patients. Increased collagen turnover, measured during ICU stay, was associated with mortality. Non-survivors displayed rising levels of collagen degradation and synthesis markers over time, whereas survivors had stable or declining levels. In non-survivors without DEX treatment, C6M and PRO-C6 levels were significantly increased, whereas these elevations were less pronounced in patients treated with DEX. Conclusion Our findings suggest that elevated collagen turnover is associated with poor outcomes in critically ill COVID-19 patients. DEX treatment appeared to attenuate ECM remodeling, although this effect was not linked to improved survival. Further studies are needed to confirm these observations and better understand the role of ECM remodeling in COVID-19 and the potential therapeutic impact of corticosteroids. |
| format | Article |
| id | doaj-art-f413177afe17487388873b1bb882d368 |
| institution | Kabale University |
| issn | 1465-993X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj-art-f413177afe17487388873b1bb882d3682025-01-26T12:48:58ZengBMCRespiratory Research1465-993X2025-01-0126111310.1186/s12931-025-03098-9Extracellular matrix turnover in severe COVID-19 is reduced by corticosteroidsJanesh Pillay0Antine W. Flikweert1Matijs van Meurs2Marco J. Grootenboers3Simone van der Sar-van der Brugge4Peter H. J. van der Voort5Morten A. Karsdal6Jannie M. B. Sand7Diana J. Leeming8Janette K. Burgess9Jill Moser10Department of Critical Care, University of Groningen, University Medical Center GroningenDepartment of Critical Care, University of Groningen, University Medical Center GroningenDepartment of Critical Care, University of Groningen, University Medical Center GroningenDepartment of Pulmonary Medicine, Amphia HospitalDepartment of Pulmonary Medicine, Amphia HospitalDepartment of Critical Care, University of Groningen, University Medical Center GroningenNordic Bioscience, Hepatic and Pulmonary ResearchNordic Bioscience, Hepatic and Pulmonary ResearchNordic Bioscience, Hepatic and Pulmonary ResearchDepartment of Pathology & Medical Biology, University of Groningen, University Medical Center GroningenDepartment of Critical Care, University of Groningen, University Medical Center GroningenAbstract Background Severe and critical COVID-19 is characterized by pulmonary viral infection with SARS-CoV-2 resulting in local and systemic inflammation. Dexamethasone (DEX) has been shown to improve outcomes in critically ill patients; however, its effect on tissue remodeling, particularly collagen turnover, remains unclear. This study investigated the association between circulating extracellular matrix (ECM) remodeling neo-epitopes and COVID-19 severity, their relationship with mortality, and the effect of DEX on these markers. Methods We conducted a multi-center prospective cohort study involving 226 COVID-19 patients: 157 with severe disease admitted to the ward and 69 with critical disease admitted to the ICU. Plasma samples were collected at ICU admission and at discharge or death. Circulating collagen degradation (C3M, C4Ma3, and C6M) and synthesis (PRO-C3, PRO-C4, and PRO-C6) neo-epitopes were measured. Longitudinal analysis of ECM neo-epitope changes during ICU stay and their association with mortality was performed, along with an evaluation of the impact of DEX treatment on these markers. Results Critically ill patients exhibited higher levels of collagen degradation (reflecting inflammatory driven ECM destruction) (C3M, C6M) and collagen synthesis (strongly related to fibroblast activity) (PRO-C3, PRO-C6) neo-epitopes than severe patients. Increased collagen turnover, measured during ICU stay, was associated with mortality. Non-survivors displayed rising levels of collagen degradation and synthesis markers over time, whereas survivors had stable or declining levels. In non-survivors without DEX treatment, C6M and PRO-C6 levels were significantly increased, whereas these elevations were less pronounced in patients treated with DEX. Conclusion Our findings suggest that elevated collagen turnover is associated with poor outcomes in critically ill COVID-19 patients. DEX treatment appeared to attenuate ECM remodeling, although this effect was not linked to improved survival. Further studies are needed to confirm these observations and better understand the role of ECM remodeling in COVID-19 and the potential therapeutic impact of corticosteroids.https://doi.org/10.1186/s12931-025-03098-9COVID-19ARDSExtracellular matrixNeo-epitopesCorticosteroids |
| spellingShingle | Janesh Pillay Antine W. Flikweert Matijs van Meurs Marco J. Grootenboers Simone van der Sar-van der Brugge Peter H. J. van der Voort Morten A. Karsdal Jannie M. B. Sand Diana J. Leeming Janette K. Burgess Jill Moser Extracellular matrix turnover in severe COVID-19 is reduced by corticosteroids Respiratory Research COVID-19 ARDS Extracellular matrix Neo-epitopes Corticosteroids |
| title | Extracellular matrix turnover in severe COVID-19 is reduced by corticosteroids |
| title_full | Extracellular matrix turnover in severe COVID-19 is reduced by corticosteroids |
| title_fullStr | Extracellular matrix turnover in severe COVID-19 is reduced by corticosteroids |
| title_full_unstemmed | Extracellular matrix turnover in severe COVID-19 is reduced by corticosteroids |
| title_short | Extracellular matrix turnover in severe COVID-19 is reduced by corticosteroids |
| title_sort | extracellular matrix turnover in severe covid 19 is reduced by corticosteroids |
| topic | COVID-19 ARDS Extracellular matrix Neo-epitopes Corticosteroids |
| url | https://doi.org/10.1186/s12931-025-03098-9 |
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