Iron Related Biomarkers Predict Disease Severity in a Cohort of Portuguese Adult Patients during COVID-19 Acute Infection

Abstract

Large variability in COVID-19 clinical progression urges the need to find the most relevant biomarkers to predict patients’ outcomes. We evaluated iron metabolism and immune response in 303 patients admitted to the main hospital of the northern region of Portugal with variable clinical pictures, from September to November 2020. One hundred and twenty-seven tested positive for SARS-CoV-2 and 176 tested negative. Iron-related laboratory parameters and cytokines were determined in blood samples collected soon after admission. Demographic data, comorbidities and clinical outcomes were recorded. Patients were assigned into five groups according to severity. Serum iron and transferrin levels at admission were lower in COVID-19-positive than in COVID-19-negative patients. The levels of interleukin (IL)-6 and monocyte chemoattractant protein 1 (MCP-1) were increased in COVID-19-positive patients. The lowest serum iron and transferrin levels at diagnosis were associated with the worst outcomes. Iron levels negatively correlated with IL-6 and higher levels of this cytokine were associated with a worse prognosis. Serum ferritin levels at diagnosis were higher in COVID-19-positive than in COVID-19-negative patients. Serum iron is the simplest laboratory test to be implemented as a predictor of disease progression in COVID-19-positive patients.

H-Ferritin Produced by Myeloid Cells Is Released to the Circulation and Plays a Major Role in Liver Iron Distribution during Infection

“…However, several aspects of the differential functions of the two peptides are still unclear and are a fascinating field of research [ 10 ]. An increase in circulating ferritin is observed in several situations of infection and inflammation [ 14 , 15 , 32 ]. However, the cellular sources and export pathways of serum ferritin remain to be elucidated.…”

“…Some authors defend that intracellular ferritin is passively released by cell death during inflammation [ 33 , 34 ], but abundant experimental evidence indicates that it can be actively released by different cell types, and several possible mechanisms were described [ 15 , 35 , 36 , 37 , 38 ]. The dogma in the field is that serum ferritin is composed exclusively of L chains [ 14 , 15 ]. However, in this work, we show that a significant proportion of circulating ferritin in M. avium -infected mice is composed of H chains.…”

“…Hyperferritinemia (increased level of serum ferritin) is one important inflammatory marker, although its contribution to pathology or infection resolution is not clear [ 10 , 14 , 15 ]. We previously showed that macrophages increase FTH1 expression when infected with M. avium , while FTL levels remain unaltered [ 16 ].…”

Research into Morphofunctional Characteristics of Erythrocytes in COVID-19 Patients

“…Abnormal iron metabolism may be one of the factors impairing the oxygen transport properties of hemoglobin, so in the work of Ana C. Moreira et al, the authors combine low serum iron, low transferrin and high IL-6 levels as important predictors of disease severity in COVID-19. The change in serum ferritin levels over time, they report, should be considered as an indicator of disease progression [6].…”

The Impact of Iron Dyshomeostasis and Anaemia on Long-Term Pulmonary Recovery and Persisting Symptom Burden after COVID-19: A Prospective Observational Cohort Study

“…The high prevalence of iron dyshomeostasis in COVID-19 was recognized early on, as hypoferremia and hyperferritinaemia are frequent findings in COVID-19 patients [7,25]. In particular, severe courses of COVID-19 are typically associated with hyperferritinaemia, and iron dyshomeostasis is a risk factor for an unfavourable COVID-19 outcome [26][27][28][29][30][31][32]. To date, it is still not clear if COVID-19-related alterations of iron handling are only a reflection of the host adapting to the acute infection or if SARS-CoV-2 per se interacts with iron homeostasis, and thus iron dyshomeostasis is a pathognomic feature of COVID-19.…”