Iron is a trace element that is used to replicate the virus and has a role in the vital functions of the body and the host's innate immune system. The mechanism of iron in COVID-19 severity is still not well understood. The aim of this study was to evaluate the association of the iron with COVID-19 severity. A case-control study was performed on 147 patients with a positive PCR test result and 39 normal individuals admitted to the Persian Gulf Martyrs Hospital in Bushehr, Iran. The iron profiles and related tests were measured along with hematological analytes. Hemoglobin (Hb), Fe, and saturated transferrin decreased in all the groups compared to the controls, but ferritin increased in the patient groups. After adjusting for age and sex, we found that increased ferritin levels augmented the odds ratio (OR) of the disease in the moderate (OR = 2.95, P = 0.007), severe (OR = 6.1, P < 0.001), and critical groups (OR = 8.34, P < 0.001). The decreased levels of Fe reduced the OR of the disease in the mild (OR = 0.96, P < 0.001), moderate (OR = 0.96, P < 0.001), severe (OR = 0.95, P < 0.001), and critical (OR = 0.98, P = 0.001) groups. Fe (AUC = 85.95, cutoff < 75.5 µg/dL, P < 0.001) and ferritin (AUC = 84.45, cutoff > 157.5 ng/dL, P < 0.001) have higher AUC for disease prognosis, but only ferritin (AUC = 74.89, cutoff > 261.5 ng/ dL, P < 0.001) has higher AUC for disease severity assays. It could be concluded that the use of iron chelators to reduce iron intake can be considered a therapeutic goal. In addition, measuring Fe and ferritin is beneficial for the diagnosis of the disease and determining its severity.
