Increased levels of ferritin on admission predicts intensive care unit mortality in patients with COVID-19

Abstract

Background: The aim of this study was to evaluate hyperferritinemia could be a predicting factor of mortality in hospitalized patients with coronavirus disease-2019 (COVID-19).

Methods: A total of 100 hospitalized patients with COVID-19 in intensive care unit (ICU) were enrolled and classified into moderate (n = 17), severe (n = 40) and critical groups (n = 43). Clinical information and laboratory results were collected and the concentrations of ferritin were compared among different groups. The association between ferritin and mortality was evaluated by logistic regression analysis. Moreover, the efficiency of the predicting value was assessed using receiver operating characteristic (ROC) curve.

Results: The amount of ferritin was significantly higher in critical group compared with moderate and severe groups. The median of ferritin concentration was about three times higher in death group than survival group (1722.25 μg/L vs. 501.90 μg/L, p < 0.01). The concentration of ferritin was positively correlated with other inflammatory cytokines, such as interleukin (IL)-8, IL-10, C-reactive protein (CRP) and tumor necrosis factor (TNF)-α. Logistic regression analysis demonstrated that ferritin was an independent predictor of in-hospital mortality. Especially, high-ferritin group was associated with higher incidence of mortality, with adjusted odds ratio of 104.97 [95% confidence interval (CI) 2.63-4185.89; p = 0.013]. Moreover, ferritin had an advantage of discriminative capacity with the area under ROC (AUC) of 0.822 (95% CI 0.737-0.907) higher than procalcitonin and CRP.

Conclusion: The ferritin measured at admission may serve as an independent factor for predicting in-hospital mortality in patients with COVID-19 in ICU.

Keywords: ALT, alanine aminotransferase; AOSD, adult-onset Still's disease; APTT, activated partial thromboplastin time; ARDS, acute respiratory distress syndrome; AST, aspartate aminotransferase; AUC, area under the curve; BUN, urea nitrogen; CAPS, catastrophic anti-phospholipid syndrome; CHD, coronary heart diseases; CK-MB, creatine kinase-MB; COVID-19; COVID-19, coronavirus disease-2019; CRP, C-reactive protein; DBP, diastolic pressure; DM, diabetes mellitus; Ferritin; FiO2, fraction of inspired oxygen; HP, hypertension; HR, heart rate; Hs-TnI, high sensitive troponin I; ICU, intensive care unit; IL, interleukin; INR, international normalized ratio; IQR, interquartile range; Inflammation markers; MAS, macrophage activation syndrome; MERS, Middle East respiratory syndrome; MOF, multiple organ failure; MV, mechanical ventilation; Mortality; NT-proBNP, N-terminal pro-B-type natriuretic peptide; PCT, procalcitonin; PT, prothrombin time; PTA, prothrombin activity; PaO2, partial pressure of arterial oxygen; RBC, red blood cells; ROC, receiver operating characteristic; RR, respiration rate; RT-PCR, reverse transcription-polymerase chain reaction; SARS, severe acute respiratory syndrome; SARS-CoV-2; SBP, systolic blood pressure; SpO2, percutaneous oxygen saturation; TNF, tumor necrosis factor; TT, plasma thrombin time; WBC, white blood cells; eGFR, ovulated glomerular filtration rate.

Fig. 1

Correlation analysis of ferritin level with that of inflammatory cytokines including IL-8, IL-10, TNF-α and CRP. A. Ferritin vs. IL-8; B. Ferritin vs. IL-10; C. Ferritin vs. CRP; D. Ferritin vs. TNF-α. Pearson correlation was used. IL-8/10 indicates interleukin-8/10; TNF-α tumor necrosis factor-α; CRP C reactive protein.

Fig. 2

Receiver operating characteristic (ROC) curve analysis was performed for prediction of mortality by ferritin, PCT and CRP levels in patients with COVID-19 during hospitalization. The PCT (- - -) had AUC of 0.75 and 95% CI (0.65–0.85); CRP (— -) had AUC of 0.71 and 95% CI (0.61–0.82). The level of ferritin (——) has a better prognosis value (AUC = 0.82, 95% CI 0.74–0.91). *The cut-off points were selected by maximum Youden index with the sum of sensitivity and specificity. PCT indicates procaicltonin; CRP indicates C reactive protein.