Nikhil Prasad Fact checked by:Thailand Medical News Team Aug 24, 2026 54 minutes ago
A new Italian study has found that severe COVID-19 is closely associated with major changes in inflammation and the way the body handles iron, potentially offering scientists a clearer picture of why some patients become critically ill.
The research involved 144 hospitalized COVID-19 patients and 139 COVID-19-negative vaccinated controls. Patients were divided into four groups, ranging from those needing no oxygen to critically ill patients requiring intensive care and intubation.
Severe COVID-19 was associated with rising inflammation and significant disruption of the body's iron-regulation
Inflammation Rises as COVID-19 Worsens
Blood tests showed striking increases in three inflammatory markers—IL-6, S100A8/A9 and C-reactive protein—in COVID-19 patients. All three were significantly higher than in controls.
More importantly, inflammation appeared connected to disease severity. Patients requiring intensive care and intubation had significantly higher IL-6 than those needing no oxygen, while S100A8/A9 was significantly elevated among patients requiring CPAP breathing support and those admitted to intensive care.
COVID-19 Dramatically Changes Iron Handling
The researchers also uncovered a distinctive iron pattern. COVID-19 patients had lower blood iron and transferrin, a protein responsible for transporting iron around the body. Meanwhile, ferritin, which stores iron, and hepcidin, a hormone controlling iron availability, were substantially higher.
This suggests that iron may remain stored inside the body but become less available for normal biological functions. Such "functional iron deficiency" could matter because immune cells require iron to work effectively.
Importantly, most differences remained highly significant when researchers repeated their analysis using age- and sex-matched groups.
Iron Changes Track with Severe Disease
This Thailand Medical News report highlights an especially important finding: critically ill patients had significantly higher ferritin and lower total transferrin than patients who did not require oxygen. However, iron, hepcidin and transferrin saturation did not significantly differ across the four severity groups.
Higher hepcidin was also associated with higher IL-6 and C-reactive protein and fewer lymphocytes. Higher iron, meanwhile, was associated with lower IL-6 and C-reactive protein, strengthening evidence of a relationship between inflammation and disrupted iron regulation.
Possible Connection to Long COVID
An exploratory analysis examined gene activity in immune cells from 11 people with long COVID, including five with brain fog and six without it. Researchers identified 2,071 differently expressed genes, with significant over-representation of genes involved in heme metabolism and inflammatory responses. These preliminary findings suggest similar biological disturbances could persist in more severe long COVID, although larger studies are needed.
Institutions Behind the Research
The institutions involved included IRCCS MultiMedica, Uni
versity of Insubria, University of Milan, IRCCS Policlinico San Donato and the University of Perugia School of Medicine, all in Italy.
Conclusion
The findings suggest that severe COVID-19 involves more than intense inflammation: it may also disrupt how iron is stored, transported and made available to cells. Larger studies are needed before these markers can be used clinically, particularly for predicting severe disease or long COVID.
The study findings were published in the peer reviewed journal: Frontiers in Immunology.
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1908452/full
Read Also:
https://www.thailandmedical.news/articles/coronavirus
https://www.thailandmedical.news/articles/long-covid 
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