covid x iron

Study points to serum iron as possible therapeutic target for severe COVID-19

Researchers writing in the journal Critical Care sought to characterise iron parameters, including serum iron, in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19), and how these related to disease severity. "This is the first study describing iron status in COVID-19. Our data suggest that serum iron may be a useful biomarker for identifying disease severity in COVID-19, whilst also being a potential therapeutic target," wrote Akshay Shah, University of Oxford, Oxford, UK, and colleagues.

In the study, investigators retrospectively evaluated any serum iron profiles that were measured in critically ill patients with COVID-19 within 24 h of admission to the ICU at John Radcliffe Hospital, Oxford, UK, between March 31 and April 25, 2020. Patients were stratified according to severity of hypoxemic respiratory failure on admission as severe (PaO2/FiO2 ratio < 100 mmHg) or non-severe (PaO2/FiO2 ratio 100–300 mmHg).

A total of 30 patients were included, with 10 considered to be severe and 20 non-severe. Overall, 17 (57%) patients were male. The median age was 57, with a range of 52 to 64 years. All 10 patients with severe hypoxemia required invasive mechanical ventilation and prone positioning. In the non-severe group, 16 (80%) of the patients required invasive ventilation and 7 (35%) required prone positioning.

Compared to patients with non-severe hypoxemia, those with severe hypoxemia had significantly lower levels of serum iron (median 2.3 μmol/L (IQR, 2.2–2.5) vs 4.3 μmol/L (IQR, 3.3–5.2), p < 0.001) and lymphocyte counts (mean (SD) 0.50 × 109/L (0.2) vs 0.87 × 109/L (0.4), p = 0.0152). The authors noted that "serum iron was lower when compared with other cohorts of non-COVID-19 ICU patients reported previously, including those with sepsis." 

Meanwhile, there were no statistically significant differences in transferrin saturation (7% (IQR, 6–12) vs 12% (IQR, 8–14), p = 0.122) and serum ferritin (903.8 mcg/L (IQR, 566.9–2789.2) vs 1566.1 mcg/L (IQR, 729–2511.5), p = 0.569) levels between groups. The proportion of patients with pulmonary emboli was numerically higher in patients with severe hypoxemia, but this was also not statistically significant.

According to the authors, the optimal Youden Index for distinguishing between severe and non-severe hypoxemia was a serum iron concentration of 2.9 μmol/L (sensitivity 0.9, specificity 1.0). They noted that the association of serum iron with lymphocyte counts could reflect the requirement of the adaptive immune response for iron and may contribute to possible T cell dysfunction reported in COVID-19. They also suggested that hypoferremia is likely to be due at least in part to inflammation-driven increases in hepcidin concentrations.

"Anti-inflammatory drugs such as tocilizumab will likely suppress hepcidin synthesis through inhibition of IL-6 and so increase serum iron. Other potential therapeutic strategies include hepcidin antagonists and hypoxia-inducible factor inhibitors," the authors said. "Additionally, unlike hepcidin and IL-6, serum iron is measured widely and so could assist with identification and monitoring of severity of disease. Our results support performing a larger study to better characterise these patterns."