key: cord-0942888-h2sztyh2
authors: Abobaker, Anis
title: Can iron chelation as an adjunct treatment of COVID-19 improve the clinical outcome?
date: 2020-06-30
journal: Eur J Clin Pharmacol
DOI: 10.1007/s00228-020-02942-9
sha: e81654bd9ab214e516c9d97a34691d28e783d424
doc_id: 942888
cord_uid: h2sztyh2

nan

A recent bioinformatic study showed that one of the important pathogenic effects of coronavirus disease 2019 (COVID-19) is through the direct damage of haemoglobin molecules by the novel coronavirus (SARS-CoV-2) [1] . The haemoglobin molecule consists of four globulin subunits: two beta chains and two alpha chains [1] . Each subunit attaches to heme which has two main components: iron and porphyrin [1] . SARS-CoV-2 attacks one of the beta chains of the haemoglobulin which leads to dissociation of iron from heme [1] . This leads to increased free iron level in the body, which could explain why most patients with COVID-19 have very high ferritin level [2] . Although the result of this study has not been fully validated, it might explain multiple aspects of the pathogenesis of COVID-19. Increased iron level in the body generates reactive oxygen species which causes oxidative stress and damage to the lung, leading to subsequent lung fibrosis and decline in the lung function [3, 4] . There is evidence shows that iron overload increases viral replication, which might have a role in the severity of the infection [5] . Infection with SARS-CoV-2 causes diffuse endothelial inflammation which leads to widespread microvascular thrombosis, organ ischemia and multi-organ failure [6] . Interestingly, an in vitro study showed that iron had a similar effect by inducing the release of endothelial inflammatory cytokines, such as IL-6 [7] . Through its iron chelation effect, deferoxamine reduces iron availability in serum and body tissue which could prevent lung injury and fibrosis following COVID-19 infection. An in vitro study showed that deferoxamine decreased the level of viral replication of some RNA viruses, such as HIV-1. Moreover, when it was combined with an antiviral drug, it led to a synergistic effect on reducing the viral replication cycle [8] . This might suggest that deferoxamine could be beneficial in adjunction with anti-viral drugs to treat Covid-19. In addition, deferoxamine decreased the level of IL-6 and endothelial inflammation in vitro, which could reduce the severity of COVID-19 infection as endothelial inflammation is one of the important factors which leads to multi-organ damage and failure [7] . Interestingly, deferoxamine has immunomodulatory effect. It improved the immune response against enteroviral infection in infected mice by inducing upregulation of B cells and increasing the level of neutralising antibody titre [9] . Therefore, deferoxamine could ameliorate the pathogenic effect of COVID-19 caused by viral-induced lymphopenia.

In conclusion, iron chelation drugs, such as deferoxamine, can be used as a supportive treatment to improve the clinical outcome and to reduce the severity of COVID-19 infection. However, multiple randomised control studies are required to test their efficacy and safety.

Funding information No financial or nonfinancial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

Conflict of interest The author declares that he has no conflict of interest.

COVID-19: attacks the 1-beta chain of hemoglobin and captures the porphyrin to inhibit human heme metabolism

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

The iron cycle and oxidative stress in the lung

Critical role for iron accumulation in the pathogenesis of fibrotic lung disease

Viral infection and iron metabolism

Endothelial cell infection and endotheliitis in COVID-19

Iron chelation and hydroxyl radical scavenging reduce the inflammatory response of endothelial cells after infection with Chlamydia pneumoniae or influenza A

Inhibition of human immunodeficiency virus type 1 replication in human mononuclear blood cells by the iron chelators deferoxamine, deferiprone, and bleomycin

Deferoxamine compensates for decreases in B cell counts and reduces mortality in enterovirus 71-infected mice