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Research Article: A biomarker-derived injury score integrating inflammatory cytokines and mitochondrial vitality may predict short-term injury risk in football

Date Published: 2026-10-15

Abstract:
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). 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-?) 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). 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). 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.

Introduction:
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).

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