key: cord-0974366-jy9jilu3
authors: Guzmán‐Castro, Salvador; Chora‐Hernandez, Luis David; Trujillo‐Alonso, Gersain; Calvo‐Villalobos, Ivan; Sanchez‐Rangel, Antonio; Ferrer‐Alpuin, Edgar; Ruiz‐Jimenez, Miguel; Corzo‐Leon, Dora E.
title: COVID‐19–associated mucormycosis, diabetes and steroid therapy: Experience in a single centre in Western Mexico
date: 2021-10-28
journal: Mycoses
DOI: 10.1111/myc.13383
sha: 7a9fb3add18d856f262d4394190d0ede841c4333
doc_id: 974366
cord_uid: jy9jilu3

BACKGROUND: COVID‐19–associated mucormycosis (CAM) has emerged as a challenging complication as the current pandemic has increased the population requiring treatment with corticosteroids. CAM has caused a massive outbreak in India, reported to be causing cases in Iran, Egypt and The Netherlands. OBJECTIVES: To describe CAM cases occurring in a single centre in Western Mexico. METHODS: Our group carried out a retrospective study from May 2020 to May 2021 to identify CAM cases in patients with previous COVID‐19 diagnosis. RESULTS: Six CAM cases occurred in a single centre in Western Mexico during the study period, most of them with diabetes (n = 5/6) and all received corticosteroid therapy even when only three had severe COVID‐19. After analysing local COVID‐19 burden, it was estimated that in this region, CAM was 300 times more frequent among COVID individuals than the estimates for general population. CONCLUSION: Similar to large reports in India and other countries, CAM cases reported in this study were diagnosed in individuals with diabetes, hyperglycaemic status and with history of previous use of corticosteroids. Identifying these individuals at risk can help the early identification of CAM. In addition, strict glycaemic control and avoidance of unnecessary corticosteroid in non‐severe COVID‐19 cases could help in preventing this complicated fungal infection.

immunosuppressive agents. Mucormycosis is one of these COVID-19-associated fungal infections that has caused a massive outbreak in India with up to 28,000 cases in less than a year. 5, 6 Increasing incidence of CAM cases has been also reported in Iran, The Netherlands and, Egypt. [7] [8] [9] Uncontrolled diabetes and newly diagnosed diabetes are main risk factor for CAM. 10 Inappropriate use of steroids in CAM individuals has estimated to be up to 63% and their use has been also identified as an independent risk factor for CAM. 5, 10 To contribute to the evidence about the epidemiology and characteristics of this infection, we report six cases of COVID-19-associated mucormycosis (CAM) in a single reference mycology Centre in Western Mexico. Table 1 and Figure 1 . Five cases were proven and, only one was considered probable as the patient died before any further diagnostic approach could be done. All ROCM cases were treated with amphotericin B deoxycholate (AMBD) at a dose of 1 mg/kg/day, and the pulmonary CAM with liposomal amphotericin B at a dose of 5 mg/kg/day. Surgery was carried out in two ROCM cases. Five of six individuals died, Table 1 .

We reported six CAM cases in patients previously receiving corticosteroids, five of which had diabetes. Even before COVID-19 pandemic, ROCM cases were mainly diagnosed among individuals with uncontrolled diabetes in Mexico. 12 The pre-COVID-19 estimated burden of mucormycosis for Mexico is 0.12/100K population. 13 In the current report, mucormycosis occurred 300 times more frequently among COVID-19 individuals. This estimate has the limitation of only considering cases occurring at the current local hospital (the biggest in Morelia city); hence, frequency is most probably underestimated. However, this estimate highlights how frequent this fungal infection is among COVID-19 managed in this area. Dexamethasone, a long-acting corticosteroid, leads to hyperglycaemia by increasing insulin resistance, gluconeogenesis and, less peripheral glucose uptake. 14 Corticosteroids can induce diabetes in the same individuals at risk of severe COVID-19 such as elderly, family history of diabetes, obesity. 14 By itself, hyperglycaemia increases the releasing of reactive oxygen species and pro-inflammatory cytokines, it also affects phagocytosis and intracellular fungal killing. 15 In addition, hyperglycaemia favours Mucorales to bind endothelial cells by increasing the expression of GRP78 (a member of the HSP70 protein family expressed in endoplasmic reticulum [ER] of cells) which is known to be the human receptor for these fungi in endothelial cells. 16 Hypotheses on what is the role of SARS-CoV-2 in the pathogenesis of mucormycosis have been proposed recently. One of these proposed mechanisms is that GRP78 acts as a co-receptor for the receptor-binding domain of SARS-CoV-2 allowing the virus to entry and infect cells. 17 Once inside the cells, SARS-CoV-2 proteins would trigger unfolded TA B L E 1 Clinical characteristics of six COVID-19-associated mucormycosis (CAM) cases in Western Mexico protein response at ER leading to higher expression and levels of GRP78 as seen in COVID-19 pneumonia patients. 18 Another proposed mechanism is the potential of SARS-CoV-2 of producing acute diabetes and hyperglycaemia as it damages and triggers apoptosis of pancreatic β cells in COVID-19 severely ill individuals. 19 All these mechanisms would perpetuate a cycle where the adequate environment for mucormycosis is favoured. In a study from India where 2826 CAM cases were reported, 87% of these cases received corticosteroids and 21% for more than 10 days. 6 Using corticosteroids for longer than 10 days is not the current recommendation of use in COVID-19 severe patients. 1 

No dedicated funding was received to carry out this research.

Authors declare no conflicts of interest. 

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COVID-19-associated mucormycosis, diabetes and steroid therapy: Experience in a single centre in Western Mexico