SARS-CoV-2 infection of erythroid progenitor cells appears to dysregulate iron metabolism and haemoglobin biosynthesis during red blood cell maturation.
German researchers, writing in Stem Cell Reviews and Reports, said the resulting impaired oxygen uptake and transportation may play a role in the severity of tissue hypoxia observed in COVID-19 patients.
The study first showed that the SARS-CoV-2 virus can infect CD71+ erythroid cells (CECs) but is unable to replicate in them.
“However, there was a strong upregulation of the mRNA levels of hepcidin anti-microbial peptide (HAMP), which codes for hepcidin, the main regulator of iron homeostasis, after SARS-CoV-2 infection in the CECs of all donors.”
The researchers then compared blood samples from healthy donors, patients recovered from COVID-19, and severe COVID-19 patients in ICUs.
It found significant decreases in the haemoglobin content, the amounts of RBCs, the haematocrit, and peripheral lymphocyte counts in the blood samples of COVID-19 patients as compared to healthy donors as well as convalescent COVID-19 patients.
“The pO2 from whole blood of severe COVID-19 patients was significantly decreased compared to the pO2 from healthy donors, whereas the pCO2 was unaffected by the SARS-CoV-2 infection,” it said.
“Parameters of iron metabolism also were altered in the plasma of COVID-19 patients compared to healthy donors and convalescent patients. While the inflammatory marker and iron-storage protein ferritin was strongly increased, the plasma iron and transferrin levels were decreased in COVID-19 patients.”
They also demonstrated that COVID-19 leads to impaired porphyrin metabolism and changes in the expression of key enzymes involved in iron and haemoglobin metabolism.
“Here, we show that haemoglobinopathy and iron overload may play an important, hitherto under-recognised role in COVID-19 pathophysiology,” the researchers said.
“Moreover, we describe alterations in haemoglobin structure in blood samples of severe COVID-19 patients.”
“Our observations support the hypothesis that the cells activate a mechanism within the innate immune defence to reduce bioavailability of iron to prevent an increasing viral load, on the one hand by storing free iron in ferritin and on the other hand by downregulation of the heme biosynthesis.”
They said experimental therapeutic interventions could include anti-oxidative strategies as well as inhibitors of hepcidin to release iron for an effective haemoglobin production.