Iron and glucose-regulated protein 78 : substantial components in the coinfection of mucormycosis and COVID-19

Abstract

The viral outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China by the end of 2019 and was declared a global pandemic in early 2020. Along with the growing number of fatalities and a lack of specific treatment, the increasing incidence of mucormycosis worried world health agencies, as it ran the risk of even more threatening outcomes for patients with coronavirus disease 2019 (COVID-19). In this context, this review aims to assemble case reports of mucormycosis and COVID-19 coinfection and discuss the virulence and the host factors involved in the progress of these infections – key aspects that might unveil potential biological targets and pharmacological approaches to treat these infectious diseases. Recently, elevated serum iron levels during SARS-CoV-2 infection have been reported in the literature. Besides being a clinical characteristic of diabetic patients, iron overload is described as a virulence factor for Rhizopus oryzae. Furthermore, the increased expression of human heat-shock protein GRP78 during iron overload and coronavirus infection display a crucial role as a mediator in Mucorales invasion and, likewise, in SARS-CoV-2. These remarkable mechanisms might explain the high incidence of mucormycosis in diabetic and COVID-19 patients and, therefore, suggest regulation of GRP78 levels, management of glucocorticoid treatment and glycemic control as potential therapeutic targets of this severe coinfection.