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Peer reviewedOpen accessCOVID-19

Inflammation and iron metabolism dysregulation as hallmarks of COVID-19 severity

Frontiers in Immunology·

Martina Mutoli, Andrea Rampin, Marzia Campanile, Alisia Madè, Elena Tagliabue, Barbara Bianchi, Lorenzo Drago, Alexis Elias Malavazos, Rosanna Cardani, Marco Ranucci, Fabio Martelli, Giuseppe Ambrosio, Gaia Spinetti

DOI
10.3389/fimmu.2026.1908452
PMID
PMCID
OpenAlex
Study type
Case-control study
Publisher
Frontiers Media SA
Article type
journal-article
Integrity
current

Why this research matters now

The findings suggest that inflammatory and iron metabolism biomarkers may help stratify COVID-19 severity and identify mechanisms underlying disease progression, including persistent pathology in severe long COVID-19.

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Structured evidence summary

Research question

The study examined the association between inflammatory markers, iron metabolism parameters, and COVID-19 disease severity, and explored whether these features also relate to long COVID-19 severity.

Study design

This was a retrospective, multicentre, case-control-cross-sectional observational study with 144 hospitalized COVID-19 patients and 139 COVID-19-negative controls enrolled at two hospitals in Lombardy, Italy. An exploratory transcriptomic analysis of publicly available PBMC data was included to assess long COVID-19.

Population and setting

The study enrolled 144 hospitalized COVID-19 patients stratified into four severity groups and 139 COVID-19-negative controls (individuals referred for vaccination) from two hospitals in Lombardy, Italy.

Main findings

COVID-19 patients showed elevated inflammatory markers (IL-6, S100A8/A9, C-reactive protein), ferritin, and hepcidin, alongside reduced serum iron, transferrin, and saturated transferrin compared to controls. Greater disease severity correlated with higher ferritin, inflammatory markers, and white blood cell and neutrophil counts, but lower total transferrin. Transcriptomic analysis revealed that alterations in iron metabolism and inflammation pathways persisted in patients with severe long COVID-19.

Public-health relevance

The findings suggest that inflammatory and iron metabolism biomarkers may help stratify COVID-19 severity and identify mechanisms underlying disease progression, including persistent pathology in severe long COVID-19.

Important limitations

This summary is limited to the supplied single-article abstract and metadata. Decision-grade interpretation requires review of the original paper, including detailed methods, statistical analyses, adjustment for confounders, and full discussion of study limitations.

GIDS interpretation

The article was linked to COVID-19 and Italy by classification metadata, and vaccination appears as a contextual descriptor for the control group rather than a primary exposure or outcome. These tags aid discoverability but do not establish that the paper addresses a current surveillance signal or public health alert.

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Related GIDS surveillance

Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.

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Evidence relationships

This article has 6 auditable classifier relationships to diseases, places, topics, and study design.

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