A biomarker-derived injury score integrating inflammatory cytokines and mitochondrial vitality may predict short-term injury risk in football
Dominik Ziehe, Björn Koos, Patrick Thon, Hartmuth Nowak, Nadine Hennigs, Kaspar Schepanek et al. · Frontiers in Sports and Active Living · 2026
Background: To determine whether a biomarker-derived injury score integrating exercise-induced cytokine responses with mitochondrial and bioenergetic readouts improves short-term injury risk stratification in professional football players compared with normalized TPL and high-intensity running distance (HIRD).
Methods: Prospective observational cohort study in elite professional football. Twenty-one professional male football players (German 2nd Bundesliga, 2023/2024 season) were assessed immediately pre- and post-training. Serum cytokines (IL-6, IL-8, IL-10, TNF-α) were measured using a multiplex immunoassay. PBMC ATP content was quantified via a luciferase-based assay, and mitochondrial vitality was approximated by the TFAM/TFB2M interaction using a proximity ligation assay. ROC analysis with Youden index was applied to derive biomarker cut-offs associated with injuries occurring within 10 days. Each exceeded cut-off contributed one point to a composite Injury score (0–6). Predictive performance was compared with normalized total player load (TPL) and, in an exploratory sensitivity analysis, high-intensity running distance (HIRD; the sum of velocity-band 5 and 6 distances).
Results: Six of 21 players sustained an injury within 10 days. Normalized TPL showed weak discriminatory performance (AUC = 0.577), and HIRD showed similarly weak discrimination in an exploratory analysis (AUC = 0.532; 95% CI 0.247–0.817). In contrast, the biomarker-derived Injury score demonstrated high discrimination (AUC = 0.939; 95% CI 0.828–1.000). Using a threshold of <4 versus ≥4, scores <4 were associated with a 93% probability of remaining injury-free (13/14), whereas scores ≥4 were associated with injury occurrence in 71% of cases (5/7).
Conclusion: A biomarker-based Injury score integrating inflammatory and mitochondrial responses to exercise showed promising performance for short-term injury risk stratification and showed higher apparent discriminatory performance than normalized TPL and HIRD in this cohort. These
Findings: suggest that individualized biological responses to training stress may provide clinically relevant information for injury risk assessment in professional football. Further prospective validation in larger cohorts is required.