Ferritin in the coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis

Abstract

Objective The coronavirus disease 2019 (COVID‐19) has rapidly developed into a pandemic. Increased levels of ferritin due to cytokine storm and secondary hemophagocytic lymphohistiocytosis were found in severe COVID‐19 patients. Therefore, the aim of this study was to determine the role of ferritin in COVID‐19. Methods Studies investigating ferritin in COVID‐19 were collected from PubMed, EMBASE, CNKI, SinoMed, and WANFANG. A meta‐analysis was performed to compare the ferritin level between different patient groups: non‐survivors versus survivors; more severe versus less severe; with comorbidity versus without comorbidity; ICU versus non‐ICU; with mechanical ventilation versus without mechanical ventilation. Results A total of 52 records involving 10 614 COVID‐19‐confirmed patients between December 25, 2019, and June 1, 2020, were included in this meta‐analysis, and 18 studies were included in the qualitative synthesis. The ferritin level was significantly increased in severe patients compared with the level in non‐severe patients [WMD 397.77 (95% CI 306.51‐489.02), P < .001]. Non‐survivors had a significantly higher ferritin level compared with the one in survivors [WMD 677.17 (95% CI 391.01‐963.33), P < .001]. Patients with one or more comorbidities including diabetes, thrombotic complication, and cancer had significantly higher levels of ferritin than those without (P < .01). Severe acute liver injury was significantly associated with high levels of ferritin, and its level was associated with intensive supportive care, including ICU transfer and mechanical ventilation. Conclusions Ferritin was associated with poor prognosis and could predict the worsening of COVID‐19 patients.

Ally in Fighting Covid-19: Magnitude of Albumin Decline and Lymphopenia (Ally) Predict Progression to Critical Disease

“…ALLY is intended to provide supplemental guidance by assessing changes in albumin and baseline lymphocyte percentage as it relates to the risk of progression to critical disease status. Other variables that were also associated with a risk for progression to critical disease status in this study and other reports included increased CRP, 17 18 ferritin, 31 neutrophil percentage, 16 17 and severe disease status on admission. 17 These variables should not be disregarded in clinical decision-making.…”

Combined lymphocyte/monocyte count, D-dimer and iron status predict COVID-19 course and outcome in a long-term care facility

“…Ferritin is a key mediator of immune dysregulation, especially under extreme hyperferritinemia, via direct immune-suppressive and pro-inflammatory effects, contributing to the cytokine storm. Previous laboratory findings highlighted that a consistent percentage of patients with elevated serum ferritin levels faced a higher probability to experience serious complications from COVID-19 [ 30 , 31 ]. Accordingly, ferroptosis, a novel programmed cell death, has been suggested as an important cause of multiple organ involvement in COVID-19 and it might serve as a new treatment target [ 32 – 36 ].…”

Haemophagocytic syndrome and COVID-19

“…The frequent description of raised ferritin levels and its association with a worse prognosis stand out in early reported studies of COVID-19 [ 6 ], with a reasonable parallelism with HLH (hyperferritinaemic syndrome associated with high mortality), and therefore, several studies have suggested a close relationship between severe COVID-19 and HLH [ 7 ]. In this review, we analyse the different types of hyperinflammatory syndromes associated with COVID-19, their similarities and differences with respect to HLH, and the degree of association between SARS-CoV-2 infection and HLH.…”