Discussion
Our results show that patients with COVID-19 pneumonia had iron deficiency even they were young. And we speculate that iron deficiency effects the lung aeration loss related to paranchimal infiltrations of COVID-19. Our data indicates that iron deficiency is associated with longer hospitalization, lower oxygenation, higher CRP and procalsitonin. We found a significant effect of iron deficiency parameters on mortality of COVID-19 pneumonia. Pre-existing iron deficiency may be a risk factor for COVID-19 pneumonia and it’s severity. Since COVID-19 patients in our study had a higher prevalence of comorbidities such as hypertension, cardiovascular disease and diabetes mellitus; reduced tissue oxygenation as a result of chronic inflammation may be the reason of iron deficiency.
Bellmann-Weiler et al. (9) claimed anemia, specifically anemia of inflammation is prevalent in patients with severe SARS-CoV-2 infection and that anemia is associated with longer hospital stays, poor clinical conditions and poor survival. Systemic inflammations are associated with increased serum ferritin levels. Serum iron and TSAT decrease early after infections, inhibiting iron availability to the pathogens (10,11).
Edeas M et al. (12) speculated that increased serum ferritin levels as a result of COVID-19 related hyper-inflammation and increased ferritin levels may lead to further tissue damage. It has been reported that hyper-inflammation in association with altered iron homeostasis may play a key role in pathogenesis of disease including viral infections (13). Hyper-ferritinemia may be associated with iron toxicity from damaged tissue releasing free iron. There is no consensus to exclude this possibility.
Iron metabolism and anemia may play an important role in multiple organ dysfunction syndrome in COVID-19. A meta-analysis suggested that hemoglobin and ferritin levels vary according tot the severity of COVID-19 as well as age, gender and presence of comorbidity. The mean diference in serum ferritin was higher in severe COVID-19 compared to moderate cases. From seven observational studies and 717 individuals, the mean difference in RBC count was lower, while RDW was higher in patients with severe COVID-19 (14).
Huang et al. (15) reported reduction in hemoglobin levels in 38.2% of hospitalized COVID-19 patients. Hemoglobin concentration is one of the most important determinants of the oxygen-carrying capacity of the blood. COVID-19 patients, could sufer from a decreased capability of hemoglobin to support the increased peripheral tissue demands for oxygen due to the hyper-metabolic states during infection. Our results supports this idea since hemoglobin of patients with COVID-19 was significantly lower than the patients with non-COVID-19 pneumonia.
Alipour R et al. (16) found out that serum iron levels were lower than normal range of patients with mild, modarate and severe COVID-19 infection. They claimed that serum iron levels of ICU admitted patients were significantly lower than others. Based on the results, they spaculated that the severity of respiratory symptoms might depend on low serum iron. Our results showed that dyspnea of patients with COVID-19 infection. In our study there was an inverse relation between iron deficiency parameters (RET-He, TSAT, iron) and radiological infiltrations, hosptalization days and inflamatory parameters (CRP, PCT) of COVID-19 patients. In the otherwise Cavezzi at al. (17) mentioned about the possible role of hemoglobin denaturation and tissue iron overload in COVID-19; potential adjuvant therapeutic interventions in a review article.
In a study by Li et al. (18) ferritin was significantly higher in severe patients. Shah et al. (19) reported no significant differences in serum ferritin levels and transferrin saturation between patients with non-severe and severe hypoxemia. They reported significantly lower levels of serum iron in patients with severe hypoxemia. In our study, there was not a significant difference in ferritin levels between COVID-19 and non-COVID-19 pneumonia but the ferritin level of severe COVID-19 pneumonia was higher.
Virus-connected iron metabolism is one of the topics have to be investigated for the development of therapeutic strategies for COVID-19. Which one might be used to treat COVID-19 infections; iron replacement treatment or iron chelators? This subject is still controversial and has to be determined in future studies.