The COVID-19 pandemic has had wide-ranging impacts on public health. One area of concern has been whether COVID-19 affects iron levels in the body. Iron is an essential mineral that is vital for many biological functions, so disruptions to iron homeostasis could have significant health consequences.
How could COVID-19 impact iron levels?
There are several ways in which COVID-19 could theoretically affect iron levels:
- Inflammation – COVID-19 often causes significant inflammation, especially in severe cases. Inflammation drives up hepcidin levels, which is the main regulator of iron. Higher hepcidin leads to decreased absorption of iron from the diet and sequestration of iron into cells.
- ACE2 receptors – The SARS-CoV-2 virus enters cells through ACE2 receptors. These receptors are found on intestinal cells that are involved in iron absorption. Viral infection of these cells could impair their ability to absorb dietary iron.
- Oxygen saturation – Many COVID-19 patients experience significant drops in oxygen saturation levels. Low oxygen can stimulate increased production of hypoxia-inducible factors that regulate iron. This could disrupt normal iron homeostasis.
- Gastrointestinal effects – COVID-19 often causes gastrointestinal symptoms like diarrhea that could reduce absorption of dietary iron.
- Blood clots – Clotting abnormalities are common in COVID-19. Microclots throughout the body might disrupt normal iron recycling and distribution.
Through these mechanisms, COVID-19 could potentially reduce iron absorption from the diet, sequester iron in cells rather than transporting it through the bloodstream, and disrupt normal iron recycling pathways.
What does the evidence say?
Given the theoretical basis for COVID-19 to impact iron homeostasis, what does the empirical evidence show?
There have been a number of studies that have measured iron parameters in COVID-19 patients. The findings have been somewhat mixed, but overall most studies have found:
- At hospital admission, iron levels tend to be normal or even elevated in COVID-19 patients compared to healthy controls.
- As the disease progresses and inflammation increases, iron levels drop and anemia often develops.
- More severe COVID-19 cases experience greater impacts on iron status and anemia compared to mild cases.
- Indicators of iron sequestration in cells and macrophages are elevated in many hospitalized COVID-19 patients.
Here is a summary of key findings from some of the studies on this topic:
| Study | Key Findings |
|---|---|
| Gomez et al. 2021 | – 51% of COVID-19 ICU patients developed anemia during hospitalization – Anemia associated with 3-fold higher mortality risk |
| Ferguson et al. 2020 | – ICU COVID-19 patients had significantly lower iron and transferrin saturation than ward patients and controls – Iron levels decreased and anemia rates increased over time in ICU patients |
| Song et al. 2021 | – Serum iron and hemoglobin decreased sharply after symptom onset in severe COVID-19 cases but remained normal in moderate cases |
| Taneri et al. 2020 | – Hospitalized COVID-19 patients had significantly lower hemoglobin, iron, and transferrin saturation compared to controls |
This emerging evidence indicates that while many COVID-19 patients start off with normal or even elevated iron levels, the inflammation and illness progression associated with severe COVID-19 frequently depletes iron stores and causes anemia.
Mechanisms of COVID-related iron changes
Given that iron perturbations and anemia are common occurrences in COVID-19, especially in advanced disease, what are the underlying mechanisms?
Several lines of evidence point to hepcidin as a key mediator of the COVID-related disruption in iron homeostasis. Hepcidin is a peptide hormone produced in the liver that regulates iron levels. In response to inflammation, hepcidin levels rise dramatically, which blocks iron absorption and causes iron sequestration.
Studies have found very high levels of hepcidin in patients with severe COVID-19. For example:
- Armitage et al. found median hepcidin concentrations in COVID-19 ICU patients to be 5 times higher than a controlgroup.
- Bellmann-Weiler et al. reported hepcidin levels in COVID-19 pneumonia patients that were roughly 8 times higher than healthy controls.
This hepcidin surge induced by COVID-related inflammation and cytokine release is likely a central mechanism leading to declining iron levels and anemia in advanced COVID-19 illness.
Other contributing factors
In addition to inflammation-driven hepcidin increases, other processes may also contribute to COVID-related iron dysregulation:
- ACE2 downregulation – Some studies have found that ACE2 expression in intestinal cells is downregulated during COVID-19, which could directly impair iron absorption.
- Gastrointestinal bleeding – Some severe cases have significant GI bleeding, which could contribute to anemia.
- Blood clots – Widespread microclots impair delivery of iron to tissues and may lead to localized iron sequestration.
- Bone marrow suppression – This can impair red blood cell production and contribute to anemia.
While inflammation and hepcidin likely play central roles, these other factors may exacerbate COVID-related declines in iron status and onset of anemia.
Conclusion
In conclusion, emerging evidence indicates that COVID-19 frequently leads to significant declines in iron levels and increased rates of anemia, especially in severe cases. The mechanisms appear to be centered around dramatically increased hepcidin production induced by COVID-related inflammation, which blocks iron absorption and causes iron sequestration in cells. This COVID-induced disruption of normal iron homeostasis may contribute to adverse outcomes, since iron is essential for many cellular functions. Correcting anemia through iron supplementation or blood transfusion in advanced COVID-19 cases may potentially help improve outcomes, but more research is needed. Careful monitoring of iron status and hemoglobin levels is warranted in COVID-19 patients.