Iron related biomarkers predict disease severity in a cohort of Portuguese adult patients during COVID-19 acute infection

Moreira, A. C.; Teles, M. J.; Silva, T.; Bento, C. M.; Alves, I. S.; Pereira, L. C.; Guimaraes, J. T.; Porto, G.; Oliveira, P.; Gomes, S.

BACKGROUND: Growing evidence indicates a link between iron metabolism and COVID-19 clinical progression, supporting the use of iron and inflammatory parameters as relevant biomarkers to predict patients' outcomes. METHODS: 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. Of these, 127 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 and, in a subgroup of patients, throughout hospitalization. Demographic data, comorbidities and clinical outcomes were recorded. Patients were assigned into 5 groups according to disease severity. RESULTS: Serum iron and transferrin levels at admission were lower in COVID-19-positive than in COVID-19-negative patients. Conversely, the levels of interleukin(IL)-6 and monocyte chemoattractant protein 1 (MCP1) 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 but did not correlate with disease severity. Longitudinal determinations of iron and ferritin made in a subgroup of patients (n=23) revealed highly variable results. CONCLUSIONS: Serum iron is the simplest laboratory test to be implemented as a predictor of disease progression in hospitalized acute COVID-19-positive patients. Variation of ferritin with time should be revisited in larger cohorts.