Anemia and iron metabolism in COVID-19: a systematic review and meta-analysis

Abstract

Iron metabolism and anemia may play an important role in multiple organ dysfunction syndrome in Coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to evaluate biomarkers of anemia and iron metabolism (hemoglobin, ferritin, transferrin, soluble transferrin receptor, hepcidin, haptoglobin, unsaturated iron-binding capacity, erythropoietin, free erythrocyte protoporphyrine, and erythrocyte indices) in patients diagnosed with COVID-19, and explored their prognostic value. Six bibliographic databases were searched up to August 3rd 2020. We included 189 unique studies, with data from 57,563 COVID-19 patients. Pooled mean hemoglobin and ferritin levels in COVID-19 patients across all ages were 129.7 g/L (95% Confidence Interval (CI), 128.51; 130.88) and 777.33 ng/mL (95% CI, 701.33; 852.77), respectively. Hemoglobin levels were lower with older age, higher percentage of subjects with diabetes, hypertension and overall comorbidities, and admitted to intensive care. Ferritin level increased with older age, increasing proportion of hypertensive study participants, and increasing proportion of mortality. Compared to moderate cases, severe COVID-19 cases had lower hemoglobin [weighted mean difference (WMD), − 4.08 g/L (95% CI − 5.12; − 3.05)] and red blood cell count [WMD, − 0.16 × 1012 /L (95% CI − 0.31; − 0.014)], and higher ferritin [WMD, − 473.25 ng/mL (95% CI 382.52; 563.98)] and red cell distribution width [WMD, 1.82% (95% CI 0.10; 3.55)]. A significant difference in mean ferritin levels of 606.37 ng/mL (95% CI 461.86; 750.88) was found between survivors and non-survivors, but not in hemoglobin levels. Future studies should explore the impact of iron metabolism and anemia in the pathophysiology, prognosis, and treatment of COVID-19.

Transcriptomic similarities and differences in host response between SARS-CoV-2 and other viral infections

“…The two genes, therefore, are both involved in an effective immune signaling between virally infected cells and the host. HFE is pleotropic in function, and it binds with the transferrin receptor thus reducing affinity for iron loaded transferrin, resulting in less cytoplasmic iron ( Taneri et al., 2020 ). ACO1 is bifunctional as well, a key modulator of mitochondrial iron metabolism, and it is also an essential enzyme in the Krebs cycle ( Wood, 2006 ).…”

Anemia and COVID‐19: A prospective perspective

“…In a meta-analysis by Taneri et al, 6 hemoglobin levels were found to be significantly lower in patients with severe COVID-19 as opposed to moderate cases (WMD, −4.08 g/L; 95% CI, −5.12 to 3.05 g/L), in agreement with the observations by Henry et al 2 Taneri et al, 6 however, also reported that lower hemoglobin levels were observed in patients with older age, a higher percentage of subjects with diabetes, hypertension, and overall comorbidities, suggesting that underlying comorbidities and ACD may play a role in this observation. In an interesting study by Bellmann-Weiler et al, 7 24.7% of COVID-19 patients had anemia at admission, similar to the rate observed in our study and that by Tao et al 1 They further reported that functional iron deficiency, defined as transferrin saturation of less than 20% and serum ferritin greater than 100 µg/L, was observed in 80.0% of patients upon admission.…”

The peripheral T cell population is associated with pneumonia severity in cynomolgus monkeys experimentally infected with severe acute respiratory syndrome coronavirus 2

“…On Days 7-10 after the initial inoculation, two monkeys from the CD3+ low group became lethargic, with decreased hemoglobin levels and RBC counts suggestive of severe anemia. In some cases of COVID-19, low hemoglobin levels indicate anemia [2,[44][45][46]. The mechanism underlying anemia in COVID-19 patients is unclear; however, virus infection and .…”

“…By contrast, an early type I IFN-related innate immune response controlled viral replication and dispersion at an early stage in the CD3+ high group.On Days 7-10 after the initial inoculation, two monkeys from the CD3+ low group became lethargic, with decreased hemoglobin levels and RBC counts suggestive of severe anemia. In some cases of COVID-19, low hemoglobin levels indicate anemia[2,[44][45][46]. The mechanism underlying anemia in COVID-19 patients is unclear; however, virus infection and --inflammation impact iron metabolism[47][48][49].…”