Hemophagocytosis, hyper-inflammatory responses, and multiple organ damages in COVID-19-associated hyperferritinemia

Abstract

Hyperferritinemia comes to light frequently in general practice. However, the characteristics of COVID-19-associated hyperferritinemia and the relationship with the prognosis were not well described. The retrospective study included 268 documented COVID-19 patients. They were divided into the hyperferritinemia group (≥ 500 µg/L) and the non-hyperferritinemia group (< 500 µg/L). The prevalence of fever and thrombocytopenia and the proportion of patients with mechanical ventilator support and in-hospital death were much higher in the hyperferritinemia group (P < 0.001). The hyperferritinemia patients showed higher median IL-6, D-dimer, and hsCRP (P < 0.001) and lowered FIB level (P = 0.036). The hyperferritinemia group had a higher proportion of patients with AKI, ARDS, and CSAC (P < 0.001). According to the multivariate analysis, age, chronic pulmonary disease, and hyperferritinemia were found to be significant independent predictors for in-hospital mortality [HR 1.041 (95% CI 1.015–1.068), P = 0.002; HR 0.427 (95% CI 0.206–0.882), P = 0.022; HR 6.176 (95% CI 2.447–15.587), P < 0.001, respectively]. The AUROC curve was 0.88, with a cut-off value of ≥ 971 µg/L. COVID-19 patients with hyperferritinemia had a high proportion of organ dysfunction, were more likely to show hyper-inflammation, progressed to hemophagocytic lymphohistiocytosis, and indicated a higher proportion of death.

Higher ferritin levels in COVID-19 patients are associated with hyperinflammation, worse prognosis, and more bacterial infections without pronounced features of hemophagocytosis

“…We have read with great interest the recently published paper by Dong et al [1] reporting associations of hyperferritinemia with adverse clinical outcomes in COVID-19 patients. Due to different clinical associations present in our cohort of mostly severe and critical COVID-19 patients treated in our institution (University Hospital Dubrava, Zagreb, Croatia) and wider overview of clinical outcomes available from the hospital registry project, we aimed to update the current report with our experience.…”