Prevalence and Predictive Value of Anemia and Dysregulated Iron Homeostasis in Patients with COVID-19 Infection

Abstract

Infections with SARS-CoV-2 can result in severe clinical manifestations. As such patients present with systemic inflammation, we studied the prevalence and predictive value of anemia of inflammation (AI) or functional iron deficiency (FID), originating from immune-mediated alterations of iron homeostasis. Within this retrospective analysis of 259 hospitalized patients with COVID-19, we found that, upon admission, 24.7% were anemic, with the majority suffering from AI (68.8%). Anemia was associated with a significantly higher in-hospital mortality (OR 3.729 (95%CI 1.739–7.995), p = 0.001) but not an increased frequency of intensive care unit (ICU) admission or need for mechanical ventilation. FID was present in 80.0% of patients upon admission, linked to more advanced inflammation and associated with significantly longer hospital stay. Notably, a ferritin/transferrin ratio > 10 predicted a five-fold higher risk of ICU admission and an eight-fold higher risk of the need for mechanical ventilation. Anemia and alterations of iron homeostasis are highly prevalent in hospitalized COVID-19 patients. Iron metabolism biomarkers and hemoglobin can contribute to risk stratification of patients, as initial anemia is associated with increased mortality, whereas alterations of iron homeostasis with a higher ferritin/transferrin ratio reflect more advanced inflammation and predicts subsequent insufficient pulmonary oxygenation with the need for ICU admission and mechanical ventilation.

Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients’ performance: a prospective observational cohort study

“…Still, retrospective analyses have rapidly expanded our knowledge about COVID-19 and resulted in the discovery of a plethora of typical features of the disease [1,27]. One of these features is the frequent emergence of disturbances of iron homeostasis in COVID-19, most prominently reflected by the high incidence of hyperferritinemia [1,14,28]. To date, it is still a matter of debate if disturbances of iron handling are just a reflection of the physiological adaption to the infectious disease or if dysregulated iron homeostasis contributes to COVID-19 pathobiology and disease outcome [15,16].…”

“…Indeed, iron is not only essential for multiple cellular processes for eucaryotes but also for microbes including viruses [8][9][10][11][12][13]. Of importance, over 80% of hospitalized patients with COVID-19 presented with inflammation-driven imbalances of iron homeostasis upon admission, which predicted an adverse clinical course [14]. As ferritin also has pro-inflammatory properties, it has been speculated whether or not hyperferritinemia in COVID-19 might contribute to its pathogenesis and severity [15][16][17].…”

The Role of Methemoglobin and Carboxyhemoglobin in COVID-19: A Review

“…Anemia can be associated with an infection and/or a systemic inflammatory reaction, termed “anemia of inflammation”, as part of the physiological reaction to the disease [ 52 , 53 ]. According to a study by Bellmann-Weiler et al [ 54 ] on 259 hospitalized patients with COVID-19, 24.7% were anemic on admission, with the majority suffering from anemia of inflammation (68.8%). During hospitalization, the percentage of patients with anemia increased (around 68.8% at day 7).…”

“…Hemolytic anemia facilitates the production process of COHb so that an increased COHb blood level can be seen as a manifestation of hemolytic anemia [ 75 ]. Since anemia and hemolysis possibly occur during the course of disease in COVID-19 patients [ 17 , 18 , 22 , 54 ], hemolytic anemia may also be responsible for their COHb elevation. Because intracellular NADPH depletion and consecutive oxidative stress with damaged erythrocytes (hemolysis) is typical for G6PD deficiency, it is not surprising that G6PD deficiency in COVID-19 patients seems to be associated with elevated MetHb and COHb levels [ 20 ].…”

Rapid antigen testing and non-infectious shedding of SARS-Cov2

“…Nonetheless, we agree with Raveh et al that we had a selected group of patients, namely those who needed hospitalization due to severe disease. As hospitalization occurred mostly several days after symptom onset [ 3 ], we cannot exactly predict whether the sensitivity of the antigen test would be in a comparable range if test samples would have been taken immediately after onset of symptoms. This is a further need for future studies as well as the evaluation of the specificity and sensitivity of antigen tests for public screening along with a professional communication of the advantages and limitations of such strategies.…”