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The role of hypoxia and inflammation in the regulation of iron metabolism and erythropoiesis in COVID‐19: The IRONCOVID study
Author(s) -
Maira Diletta,
Duca Lorena,
Busti Fabiana,
Consonni Dario,
Salvatici Michela,
Vianello Alice,
Milani Angelo,
Guzzardella Amedeo,
Di Pierro Elena,
Aliberti Stefano,
Baldini Itala Marina,
Bandera Alessandra,
Blasi Francesco,
Cassinerio Elena,
Cesari Matteo,
Fracanzani Anna Ludovica,
Grasselli Giacomo,
Graziadei Giovanna,
Lombardi Rosa,
Marchi Giacomo,
Montano Nicola,
Monzani Valter,
Peyvandi Flora,
Proietti Marco,
Sandri Maria,
Valenti Luca,
Cappellini Maria Domenica,
Girelli Domenico,
Protti Alessandro,
Motta Irene
Publication year - 2022
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.26679
Subject(s) - hepcidin , erythropoiesis , hypoxia (environmental) , erythropoietin , medicine , anemia , inflammation , physiology , intensive care , systemic inflammation , immunology , intensive care medicine , chemistry , organic chemistry , oxygen
Coronavirus Disease (COVID‐19) can be considered as a human pathological model of inflammation combined with hypoxia. In this setting, both erythropoiesis and iron metabolism appear to be profoundly affected by inflammatory and hypoxic stimuli, which act in the opposite direction on hepcidin regulation. The impact of low blood oxygen levels on erythropoiesis and iron metabolism in the context of human hypoxic disease (e.g., pneumonia) has not been fully elucidated. This multicentric observational study was aimed at investigating the prevalence of anemia, the alterations of iron homeostasis, and the relationship between inflammation, hypoxia, and erythropoietic parameters in a cohort of 481 COVID‐19 patients admitted both to medical wards and intensive care units (ICU). Data were collected on admission and after 7 days of hospitalization. On admission, nearly half of the patients were anemic, displaying mild‐to‐moderate anemia. We found that hepcidin levels were increased during the whole period of observation. The patients with a higher burden of disease (i.e., those who needed intensive care treatment or had a more severe degree of hypoxia) showed lower hepcidin levels, despite having a more marked inflammatory pattern. Erythropoietin (EPO) levels were also lower in the ICU group on admission. After 7 days, EPO levels rose in the ICU group while they remained stable in the non‐ICU group, reflecting that the initial hypoxic stimulus was stronger in the first group. These findings strengthen the hypothesis that, at least in the early phases, hypoxia‐driven stimuli prevail over inflammation in the regulation of hepcidin and, finally, of erythropoiesis.