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      Spectrum of Mucormycosis Before and During COVID-19: Epidemiology, Diagnosis, and Current Therapeutic Interventions

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          Abstract

          Purpose of Review

          More than half a billion people have been infected and 6.2 million killed by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) since the start of the pandemic in 2019. Systemic glucocorticoids are a double-edged sword, on the one hand, life-saving in treating COVID-19 complications while on the other hand, potentially leading to life-and-limb-threatening opportunistic fungal infections. Mucormycosis (MM) is caused by the mucormycetes family. Although rare, it is characterized by high mortality and significant morbidity. The gross similarities observed with other fungal infections which respond to different treatment regimens have made it all the more imperative to quickly and sensitively diagnose and treat MM. This review discusses the epidemiology of MM before and during the COVID-19 pandemic, associated risk factors, COVID-19-associated MM, diagnosis, and current therapeutic interventions.

          Recent Findings

          There has been a widespread and worrisome trend of rising in cases of MM, worldwide, but more so in the Indian subcontinent, where it is nicknamed the “black fungus.” This upsurge has picked up the pace ever since the start of the COVID-19 pandemic. Necrosis is secondary to the angio-invasive and pro-thrombotic nature of the mold resulting in extensive lesions presenting mostly as rhino-orbital MM (ROM) and rhino-orbito-cerebral MM (ROCM). Infection is mostly observed in subjects with underlying risk factors such as uncontrolled diabetes, those receiving hematopoietic stem cell transplant, and/or on corticosteroid or immunosuppressive therapy, although it is widely suspected that other factors such as iron and zinc may play a role in the pathogenesis of MM. The “One world one guideline” strategy advocates both prophylactic anti-fungal therapy along with aggressive, prompt, and individualized treatment with anti-fungal drugs such as amphotericin B in addition to vigorous surgical intervention. High-risk groups need particularly rapid diagnosis although empirical anti-fungal therapy may not be delayed. Speeding diagnostic turnaround times are essential to institute early therapy, and there is much scope for newer modalities such as PCR, matrix-assisted laser desorption ionization-time of flight mass spectrometry, and whole-genome sequencing in such endeavors. The results of strict monitoring of blood glucose levels along with rational and limited use of steroids and immunomodulatory drugs have proven to be a significant preventive measure.

          Summary

          The significant rise in cases of MM worldwide has necessitated viewing each case with a strong index of suspicion. Adoption of rapid diagnostics, early antifungal therapy, and prompt surgical interventions are essential, while high-risk groups need particular focused care which may include prophylactic anti-fungal therapy, limited steroid use, and meticulous control of the underlying disease. Developing quicker and more sensitive diagnostic modalities has great potential to improve the detection and management of MM.

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          Most cited references81

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          Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis

          Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support.
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            Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group.

            Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.
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              Epidemiology and outcome of zygomycosis: a review of 929 reported cases.

              Zygomycosis is an increasingly emerging life-threatening infection. There is no single comprehensive literature review that describes the epidemiology and outcome of this disease. We reviewed reports of zygomycosis in the English-language literature since 1885 and analyzed 929 eligible cases. We included in the database only those cases for which the underlying condition, the pattern of infection, the surgical and antifungal treatments, and survival were described. The mean age of patients was 38.8 years; 65% were male. The prevalence and overall mortality were 36% and 44%, respectively, for diabetes; 19% and 35%, respectively, for no underlying condition; and 17% and 66%, respectively, for malignancy. The most common types of infection were sinus (39%), pulmonary (24%), and cutaneous (19%). Dissemination developed in 23% of cases. Mortality varied with the site of infection: 96% of patients with disseminated disease died, 85% with gastrointestinal infection died, and 76% with pulmonary infection died. The majority of patients with malignancy (92 [60%] of 154) had pulmonary disease, whereas the majority of patients with diabetes (222 [66%] of 337) had sinus disease. Rhinocerebral disease was seen more frequently in patients with diabetes (145 [33%] of 337), compared with patients with malignancy (6 [4%] of 154). Hematogenous dissemination to skin was rare; however, 78 (44%) of 176 cutaneous infections were complicated by deep extension or dissemination. Survival was 3% (8 of 241 patients) for cases that were not treated, 61% (324 of 532) for cases treated with amphotericin B deoxycholate, 57% (51 of 90) for cases treated with surgery alone, and 70% (328 of 470) for cases treated with antifungal therapy and surgery. By multivariate analysis, infection due to Cunninghamella species and disseminated disease were independently associated with increased rates of death (odds ratios, 2.78 and 11.2, respectively). Outcome from zygomycosis varies as a function of the underlying condition, site of infection, and use of antifungal therapy.
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                Author and article information

                Contributors
                mansoorshafi21@gmail.com
                Journal
                Curr Fungal Infect Rep
                Curr Fungal Infect Rep
                Current Fungal Infection Reports
                Springer US (New York )
                1936-3761
                1936-377X
                10 August 2022
                : 1-12
                Affiliations
                [1 ]GRID grid.414739.c, ISNI 0000 0001 0174 2901, Advanced Centre for Human Genetics, , Sher-I-Kashmir Institute of Medical Sciences, ; Soura, Srinagar, Kashmir 190011 India
                [2 ]GRID grid.414739.c, ISNI 0000 0001 0174 2901, Department of Clinical Biochemistry, , Sher-I-Kashmir Institute of Medical Sciences, ; Soura, Srinagar, Kashmir 190011 India
                [3 ]GRID grid.414739.c, ISNI 0000 0001 0174 2901, Department of General Medicine, , Sher-I-Kashmir Institute of Medical Sciences, ; Soura, Srinagar, Kashmir 190011 India
                [4 ]GRID grid.413219.c, ISNI 0000 0004 1759 3527, Department of Pathology, , Government Medical College Srinagar, ; Srinagar, 191010 J&K India
                [5 ]GRID grid.444476.1, ISNI 0000 0004 1774 5009, Division of Biochemistry, , Sher-E-Kashmir University of Agricultural Sciences and Technology of Jammu, ; Jammu, 180009 J&K India
                [6 ]GRID grid.414739.c, ISNI 0000 0001 0174 2901, Department of Radiology, , Sher-I-Kashmir Institute of Medical Sciences, ; Soura, Srinagar, Kashmir 190011 India
                Author information
                http://orcid.org/0000-0003-1902-4611
                Article
                438
                10.1007/s12281-022-00438-w
                9364274
                b4a2b7ef-d063-4b84-bd88-e98f6727103d
                © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 1 August 2022
                Categories
                COVID-19 and Fungal Infections (RPL Kodiyanplakkal, Section Editor)

                Infectious disease & Microbiology
                covid-19,mucormycosis,epidemiology,pathogenesis,risks,management
                Infectious disease & Microbiology
                covid-19, mucormycosis, epidemiology, pathogenesis, risks, management

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