Elevation of serum ferritin levels for predicting a poor outcome in hospitalized patients with influenza infection

Abstract

Objectives: There is increasing evidence that ferritin is a key marker of macrophage activation, but its potential role in influenza infection remains unexplored. Our aim was to assess whether hyperferritinaemia (ferritin 500 ng/mL) could be a marker of poor prognosis in hospitalized patients with confirmed influenza A infection. Methods: We prospectively recruited all hospitalized adult patients who tested positive for the influenza A rRT-PCR assay performed on respiratory samples in two consecutive influenza periods (2016e17 and 2017e18). Poor outcome was defined as the presence of at least one of the following: respiratory failure, admission to the intensive care unit, or in-hospital mortality. Results: Among 494 patients, 68 (14%) developed poor outcomes; 112 patients (23%) had hyperferritinaemia (39/68, 57% in the poor-outcome group versus 73/426, 17% in the remaining patients, p < 0.0001). Median serum ferritin levels were significantly higher in the subgroup of patients with poor outcomes (609 ng/mL, range 231e967 versus 217 ng/mL, range 140e394, p < 0.0001). In multivariate analysis, hyperferritinaemia was associated with a five-fold increase in the odds ratio of developing poor outcome. After adjusting for classic influenza risk factors, ferritin remained as a significant predictive factor in all exploratory models. Ferritin levels had a good discriminative capacity with an area under the ROC curve of 0.72 (95% confidence interval (CI) 0.65e0.8, p < 0.001) and an overall diagnostic accuracy for predicting poor outcome of 79.3% (95%CI 75.4e82.7%). Conclusions: Serum ferritin may discriminate a subgroup of patients with influenza infection who have a higher risk of developing a poor outcome.

<p>Characteristics, Outcomes and Indicators of Severity for COVID-19 Among Sample of ESNA Quarantine Hospital’s Patients, Egypt: A Retrospective Study</p>

“…10,30,34 Binding and storage of iron are functions of ferritin which are also associated with immune and inflammatory responses. 35 The increase in the serum ferritin levels following bacterial or viral infection could be attributed to iron release into the reticuloendothelial system, and increased intracellular ferritin synthesis and release, with the decreased ability of ferritin transport into spleen and liver. 36 Human angiotensin-converting enzyme 2 (ACE-2) receptor binding is one of the mechanisms by which COVID-19 can invade the human body with subsequent increased expression of ACE-2 in hepatocytes.…”

Utility of Ferritin, Procalcitonin, and C-reactive Protein in Severe Patients with 2019 Novel Coronavirus Disease

“…In the present analysis, we firstly evaluated serum ferritin levels in COVID-19, which are significantly elevated during critical infection. The function of ferritin including iron binding and storage is associated with the immune and inflammatory response 16 . The reasons of increased ferritin include bacterial and/or viral infection, hemochromatosis and long-term transfusion 17 .…”

“…Previous review has also proposed a model that the inflammatory response to viral (IL-18/ferritin) presents as specific plasma patterns of immune biomarkers 17 . Moreover, elevation of serum ferritin levels predicts a poor outcome in hospitalized patients with influenza infection 16 . In the present study, the patients in severe and very severe COVID-19 both exhibits increase serum ferritin level, but the serum ferritin in very severe COVID-19 group is significantly higher than that of severe COVID-19 group.…”

SARS-CoV-2, the autoimmune virus

“…Overproduction of cytokines by macrophages has been shown to enhance the inflammatory process and to trigger unusually large amount of ferritin in the blood (‘hyperferritenemia’) [ [7] , [8] , [9] ]. Importantly, it was shown recently that on admission to hospitals, SARS-CoV-2 infected patients have high level of ferritin [ 10 , 11 ]. In light with this, it is worth mentioning that cytokine storm and hyperferitenemia have been previously shown to be triggered by other pathogenic viruses such as influenza and dengue [ 10 , 12 ].…”

“…Importantly, it was shown recently that on admission to hospitals, SARS-CoV-2 infected patients have high level of ferritin [ 10 , 11 ]. In light with this, it is worth mentioning that cytokine storm and hyperferitenemia have been previously shown to be triggered by other pathogenic viruses such as influenza and dengue [ 10 , 12 ].…”