Fibroblast activity biomarkers are associated with mortality in severe COVID-19: a post-hoc analysis of a phase 2 clinical trial
6 affiliations
- 1Nordic Bioscience, Herlev, Denmark
- 2Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
- 3GSK, Stevenage, UK
- 4GSK, Dublin, Ireland
- 5GSK, Brentford, UK
- 6GSK, Upper Providence, PA USA
Abstract
Background: Coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease characterised by systemic inflammation and lung tissue damage. In injured lungs, fibroblast activity increases in response to tissue insult and has been shown to be prognostic in fibrotic disease. This study investigated whether fibroblast activity is associated with mortality in severe COVID-19.
Method: Severe COVID-19 patients were enrolled in the randomised, sequential, multicentre, placebo-controlled, double-blind study Otilimab in severe COVID-19-related disease (OSCAR; NCT04376684). In this post-hoc analysis, serum samples from 242 placebo-treated patients were analysed on days 1, 7, and 14, alongside serum from 20 healthy controls. Two serological biomarkers reflecting fibroblast activity, PRO-C3 and PRO-C6, were quantified using ELISAs.
Results: Patients who died or experienced respiratory failure had higher PRO-C3 and PRO-C6 serum levels on day 1 compared with healthy controls (p < 0.0001 and p = 0.053, respectively) and recovering patients (both p < 0.0001). Levels gradually increased over 14 days, with the sharpest increase seen at the last measured timepoint before death. High PRO-C3 and PRO-C6 levels on day 1 were associated with increased risk of mortality (hazard ratio [HR]: 2.93, 95% confidence interval [CI]: 1.6–5.4, p = 0.0006 and HR: 3.88, 95% CI: 1.96–7.70, p = 0.0001, respectively).
Conclusion: Elevated PRO-C3 and PRO-C6 levels, and their increase shortly before death, were strongly associated with mortality in severe COVID-19. These findings highlight fibroblast activity as a key driver of poor outcomes and suggest that PRO-C3 and PRO-C6 could serve as early prognostic biomarkers to identify high-risk patients and guide future disease management strategies.
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BibTeX
@article{breisnes2026fibroblast,
title = {{Fibroblast activity biomarkers are associated with mortality in severe COVID-19: a post-hoc analysis of a phase 2 clinical trial}},
author = {Helene Wallem Breisnes and Filipa Bica Simões and Peder Frederiksen and Signe Holm Nielsen and Diana Julie Leeming and Tony Cahn and Ciara O’Shea and Kai Hove and Mark Layton and Morten Asser Karsdal and Anne-Christine Bay-Jensen and Jannie Marie Bülow Sand and Sumanta Mukherjee},
journal = {Respiratory Research},
year = {2026},
month = jun,
doi = {10.1186/s12931-026-03785-1},
url = {https://doi.org/10.1186/s12931-026-03785-1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Fibroblast activity biomarkers are associated with mortality in severe COVID-19: a post-hoc analysis of a phase 2 clinical trial
AU - Helene Wallem Breisnes
AU - Filipa Bica Simões
AU - Peder Frederiksen
AU - Signe Holm Nielsen
AU - Diana Julie Leeming
AU - Tony Cahn
AU - Ciara O’Shea
AU - Kai Hove
AU - Mark Layton
AU - Morten Asser Karsdal
AU - Anne-Christine Bay-Jensen
AU - Jannie Marie Bülow Sand
AU - Sumanta Mukherjee
PY - 2026
DA - 2026/06/25
JO - Respiratory Research
DO - 10.1186/s12931-026-03785-1
UR - https://doi.org/10.1186/s12931-026-03785-1
AB - Background: Coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease characterised by systemic inflammation and lung tissue damage. In injured lungs, fibroblast activity increases in response to tissue insult and has been shown to be prognostic in fibrotic disease. This study investigated whether fibroblast activity is associated with mortality in severe COVID-19. Method: Severe COVID-19 patients were enrolled in the randomised, sequential, multicentre, placebo-controlled, double-blind study Otilimab in severe COVID-19-related disease (OSCAR; NCT04376684). In this post-hoc analysis, serum samples from 242 placebo-treated patients were analysed on days 1, 7, and 14, alongside serum from 20 healthy controls. Two serological biomarkers reflecting fibroblast activity, PRO-C3 and PRO-C6, were quantified using ELISAs. Results: Patients who died or experienced respiratory failure had higher PRO-C3 and PRO-C6 serum levels on day 1 compared with healthy controls (p < 0.0001 and p = 0.053, respectively) and recovering patients (both p < 0.0001). Levels gradually increased over 14 days, with the sharpest increase seen at the last measured timepoint before death. High PRO-C3 and PRO-C6 levels on day 1 were associated with increased risk of mortality (hazard ratio [HR]: 2.93, 95% confidence interval [CI]: 1.6–5.4, p = 0.0006 and HR: 3.88, 95% CI: 1.96–7.70, p = 0.0001, respectively). Conclusion: Elevated PRO-C3 and PRO-C6 levels, and their increase shortly before death, were strongly associated with mortality in severe COVID-19. These findings highlight fibroblast activity as a key driver of poor outcomes and suggest that PRO-C3 and PRO-C6 could serve as early prognostic biomarkers to identify high-risk patients and guide future disease management strategies.
SN - 1465-9921
SN - 1465-993X
ER -