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

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.

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

10.1101/2021.09.09.21263251 ◽

2021 ◽

Author(s):

Ana C. Moreira ◽

Maria Jose Teles ◽

Tania Silva ◽

Clara M. Bento ◽

Ines Simoes Alves ◽

...

Keyword(s):

Disease Severity ◽

Iron Metabolism ◽

Serum Iron ◽

Demographic Data ◽

Acute Infection ◽

Northern Region ◽

Monocyte Chemoattractant Protein 1 ◽

Inflammatory Parameters ◽

Clinical Pictures ◽

Worse Prognosis

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.

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Human herpesvirus 8 acute infection of endothelial cells induces monocyte chemoattractant protein 1–dependent capillary-like structure formation: role of the IKK/NF-κB pathway

Blood ◽

10.1182/blood-2006-03-012500 ◽

2006 ◽

Vol 109 (7) ◽

pp. 2718-2726 ◽

Cited By ~ 36

Author(s):

Elisabetta Caselli ◽

Simona Fiorentini ◽

Carla Amici ◽

Dario Di Luca ◽

Arnaldo Caruso ◽

...

Keyword(s):

Endothelial Cells ◽

Structure Formation ◽

Acute Infection ◽

Human Herpesvirus ◽

Productive Infection ◽

Human Herpesvirus 8 ◽

Monocyte Chemoattractant Protein 1 ◽

Herpesvirus 8 ◽

Monocyte Chemoattractant ◽

Monocyte Chemoattractant Protein

AbstractHuman herpesvirus 8 (HHV-8) is considered the causative agent of Kaposi sarcoma, a highly vascularized neoplasm characterized by spindle-shaped cells of endothelial origin and inflammatory cell infiltration. The cell transforming ability of HHV-8 has been associated with the activation of NF-κB, a nuclear factor playing a pivotal role in promoting inflammation and cell proliferation; however, little is known about NF-κB activation during acute HHV-8 infection. In the present study, we used a recently established in vitro model of HHV-8 acute productive infection in endothelial cells to investigate the effect of HHV-8 on NF-κB activity and function. HHV-8 rapidly and potently induced NF-κB activity in endothelial cells via stimulation of the IκB kinase (IKK). Following IKK activation, HHV-8 selectively triggered the production of high levels of monocyte chemoattractant protein 1 (MCP-1), whereas it did not affect the expression of other NF-κB–dependent proinflammatory proteins, including TNF-α, IL-8, and RANTES. Deletion of NF-κB–binding sites in the MCP-1 enhancer resulted in significant inhibition of HHV-8–induced transcription. Furthermore, MCP-1 production was accompanied by virus-induced capillary-like structure formation at early stages of infection. The results suggest that HHV-8–induced MCP-1 may play an important role in promoting inflammation and pathogenic angiogenesis typical of HHV-8–associated lesions.

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