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

Taneri, P. E.; Gomez-Ochoa, S. A.; Llanaj, E.; Raguindin, P. F.; Rojas, L. Z.; Wyssmann, B. M.; Kopp-Heim, D.; Hautz, W. E.; Eisenga, M. F.; Franco, O. H.; Glisic, M.; Muka, T.

Iron metabolism and anemia may play an important role in multiple organ dysfunction syndrome in Coronavirus disease 2019 (COVID-19). If confirmed, this has important implications for the more than 1.62 billion people estimated to have anemia globally. 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 prevalence of anemia) in patients diagnosed with COVID-19, and explore their prognostic value. Six bibliographic databases were searched up to May 5th 2020. We included 56 unique studies, with data from 14,044 COVID-19 patients (59 years median age). Pooled mean hemoglobin and ferritin levels in COVID-19 patients across all ages were 130.41 g/L (95% Confidence Interval (CI), 128.42; 132.39) and 673.91 ng/mL (95% CI, 420.98; 926.84), respectively. Hemoglobin levels decreased with advancing age and increasing percentage of comorbid and critically ill patients, while levels of ferritin increased with increasing male proportion and mean hemoglobin levels. Compared to moderate cases, severe cases had lower pooled mean hemoglobin [weighted mean difference (WMD), -4.21 (95% CI -6.63; -1.78)] and higher ferritin [WMD, -730.55 ng/mL (95% CI 413.24; 1047.85)]. A significant difference in mean ferritin level of 1027.23 ng/mL (95% CI 819.53; 1234.94) was found between survivors and non-survivors, but not in hemoglobin levels. No studies provided information on anemia or other biomarkers of interest. Future studies should explore the impact of iron metabolism and anemia and in the pathophysiology, prognosis, and treatment of COVID-19.