Last update and review: April 14, 2020.
Anemia is one of the hematologic findings in patients with COVID-19 related pneumonia. There are speculations that erythrocytes may be infected by SARS-CoV-2 which would explain or contribute to anemia. However, we should not forget that there is a potent innate immune response, hepcidin-mediated iron sequestration, that also results in anemia, “anemia of inflammation” (1).
There is a good relevant description of the underlying mechanisms in a model of bacterial pneumonia. The role of IL-6 is well explained. Michels et al., 2017 (2):
Although hepcidin-independent mechanisms of hypoferremia have been reported after challenge with inflammatory stimuli (23, 25, 41), we found that hypoferremia during pneumonia was completely abrogated in hepcidin-deficient mice, and in fact, plasma iron levels became elevated following infection in hepcidin-deficient mice. Our use of an infectious agent, rather than sterile inflammatory stimuli used in other reports, may account for this difference. We speculate that this increase in plasma iron levels reflects decreases in iron consumption by cytokine-suppressed erythropoiesis (24) and release of iron from intracellular sources damaged by infection, such as the liver (42). We thus propose a model in which infections result in a tendency toward increased extracellular iron that benefits the pathogen, and the protective role of inflammation-mediated hepcidin induction is to counteract this phenomenon. Furthermore, while hepcidin can be produced by leukocytes, airway epithelial cells and other tissues(19–21), our results indicate that hepcidin is predominantly produced by the liver and circulates systemically in the context of bacterial pneumonia. Consistent with this, we observed that hepcidin induction was dependent on IL-6, similar to observations with other systemic inflammatory stimuli (43). In addition, we found that IL-6 neutralization disrupted host defense against K.pneumoniae (Figure 3A), in corroboration with previous reports (22). While IL-6 induces many acute phase reactants, such as C reactive protein, which are crucial to the innate immune response, we speculate that hepcidin induction may be a component of IL-6–mediated protection.
Selected references.
1. Ganz. International Journal of Hematology volume 107, pages7–15(2018)
2. Michels KR, Zhang Z, Bettina AM, et al. Hepcidin-mediated iron sequestration protects against bacterial dissemination during pneumonia. JCI Insight. 2017;2(6):e92002. Published 2017 Mar 23. doi:10.1172/jci.insight.92002
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