Hepcidin dynamics predict outcomes in COVID-19 patients treated with interleukin inhibitors

Introduction : iron metabolism and its key regulatory hormone, hepcidin, play a pivotal role in infection and inflammation. However, the prognostic value of iron related markers in SARS-CoV-2 infection remains poorly defined. Methods : We conducted a retrospective observational study examining a cohort of 30 patients admitted between March and April 2020 for COVID-19 infection. Serial measurements of hepcidin and other iron-related parameters were obtained at baseline, day 3, and day 7 after administration of anti-IL-1 receptor or anti-IL-6-receptor therapies. The primary outcome was in-hospital mortality. Results : Baseline iron and inflammatory markers did not differ significantly between survivors and non-survivors. Hepcidin levels correlated positively with C-reactive protein (r = 0.57, p < 0.001) and inversely with serum iron (r = − 0.3, p = 0.006) at baseline day 3 day post-treatment. Importantly, the percentage change in hepcidin from baseline to day 3 after anti-IL therapy was the only independent predictor of in-hospital mortality in multivariate analysis. A hepcidin decrease ≤ 39% showed a specificity of 85.7 (95% CI 42.1–99.6) and a sensitivity of 73.9 (95% CI, 51.6–89.8) for predicting mortality.Conclusions:Hepcidin dynamics are strongly associated with clinical outcomes in COVID-19. Monitoring hepcidin trends may provide a simple, reliable tool for risk stratification in patients treated with interleukin inhibitors, and could complement established biomarkers in infection management.