Meta-analysis from 189 studies indicate alerted levels of iron and anemia biomarkers in Covid-19

21.08.2020 – A new study led by researchers at the Institute of Social and Preventive Medicine in Bern Switzerland within an international collaboration (Bucaramanga, Colombia; Debrecen, Hungary; Groningen, the Netherlands; Istanbul, Turkey; Manila, Philippines and Notwil, Switzerland), has found that patients with severe COVID-19 or those who did not survive this infection had differences in levels of iron and anemia biomarkers, compared to those with less severe disease or those who survived, respectively. The study was published at the European Journal of Epidemiology.

Changes in iron levels have been associated with worsening disease for other viral infections such as HIV and Hepatitis C, but this is the first updated and comprehensive study to elucidate a similar association for COVID-19, using several iron metabolism biomarkers.

Iron is needed to form hemoglobin, part of red blood cells that carry oxygen and remove carbon dioxide (as a waste product) from the human body. Iron storage can be found mainly binded to hemoglobin, stored as ferritin and hemosiderin in the bone marrow, spleen, and liver.

The current work is the first updated and comprehensive systematic review and meta-analyses exploring the potential clinical utility of anemia and iron metabolism in COVID-19. Based on data from 189 studies and 57,563 COVID-19 patients across all ages, researchers found a pooled mean hemoglobin level of 129.7 g/L, which decreased with older age and a higher proportion of comorbid illness and disease severity. Pathological values of ferritin were found in most COVID-19 patients, more common among males, elderly and individuals with hypertension. Major differences in ferritin levels were reported between different levels of COVID-19 severity, and among patients who survived and those who did not. In addition, compared to moderate COVID-19 cases, severe patients had worst erythrocytes phenotypes, including lower red blood cell count and higher red blood cell distribution width. Due to limited evidence and/or heterogeneity among included studies, researchers were not able to meta-analyse the evidence on other biomarkers of iron metabolism and anemia.

In addition, drawing from the findings authors have hypothesized a new mechanistic approach in evaluating the pathophysiological role of iron metabolism in COVID-19. Since, iron is essential for the growth of pathogens, but also for the body’s own immune response, during an infection, the immune system seems to ‘compete’ with the pathogen for iron. According to the findings of this work there are two potential pathways through which iron metabolism may be involved in the pathophysiology of COVID-19: 1) the virus inflicts hypoxia via direct deleterious effects on the respiratory system, altering the inflammatory response leading to anemia; and 2) the innate immune system may aim to decrease the bioavailability of iron in order to prevent an expanding viral load in the acute-phase of the infection. This leads to the activation of hepcidin, sequestration of iron within cells, increased levels of ferritin and decreased hemoglobin, culminating in hypoxia.

Overall this study suggests that hemoglobin and ferritin levels vary according to the severity of COVID-19 as well as age, gender and presence of comorbidity among COVID-19 patients. Whether hemoglobin and ferritin can be used for prognostic purposes, or have further implications for identifying novel treatment targets, needs further investigation.