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and the material was sent for histological examination&#44; which showed coenocytic hyaline hyphae with a 90&#8239;&#176; angle &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; and for fungal culture&#44; which showed growth of <span class="elsevierStyleItalic">Rhizopus sp&#46;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; The colony was sent for identification of the isolate by PCR&#44; and the regions of the internal transcribed spacer &#40;ITS&#41; were amplified using the ITS4 and ITS5 regions of the 5&#46;8S gene of the fungus ribosomal DNA &#40;rDNA&#41;&#44; which identified the agent <span class="elsevierStyleItalic">Rhizopus microsporus var&#46; microsporus</span>&#46; After treatment with liposomal Amphotericin B and compensation of the underlying disease&#44; the patient developed a worsening clinical picture&#44; requiring a second surgical approach with ocular enucleation and extensive surgical debridement&#46; The patient had a good evolution&#44; with progressive improvement&#44; and was discharged after 66 days of hospitalization under outpatient follow-up for aesthetic adjustment&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Mucormycosis is a rare&#44; opportunistic&#44; globally distributed fungal disease whose physiopathology is centered on angioinvasion that leads to tissue necrosis&#46; Among the most often described etiological agents are the coenocytic fungi of the <span class="elsevierStyleItalic">Rhizopus</span> and <span class="elsevierStyleItalic">Mucor</span> genera&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Because it is an ubiquitous and saprophytic fungus&#44; the infection usually occurs in patients with a disease that favors immunosuppression&#44; with DM being the most common one&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> The most frequent clinical form is the rhino-orbito-cerebral type&#44;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;4</span></a> which has a poor prognosis and shows better rates when amphotericin B is associated with extensive surgical excision of the infected tissue&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In a study conducted before the COVID-19 pandemic&#44; 71&#37; of the world&#39;s cases of mucormycosis were reported in India&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In a recent study carried out in the same country&#44; 1&#46;8&#37; of COVID-19 patients developed mucormycosis&#44; of which 76&#46;6&#37; of these co-infected patients were diabetics&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> These rates are not surprising&#44; as India ranks second in the world in absolute numbers of people with DM&#44; which is the main risk factor for mucormycosis&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">SARS-CoV-2 also promotes changes in the host&#44; especially in the severe forms of infection&#44; favoring the development of mucormycosis agents&#46; Among them are the direct damage to pancreatic cells&#44; causing acute DM and ketoacidosis&#44; the use of corticosteroids&#44; which alter glycemic homeostasis and indirectly favor the progression of mycosis&#44; the alteration of iron metabolism leading to an internal environment with high rates of ferritin&#44; a key factor for the development of the fungus&#44; and finally&#44; endothelitis caused directly by the virus&#44; facilitating fungal angioinvasion&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The case described herein maintains the classic line of mucormycosis presentation&#44; the rhino-orbito-cerebral type&#44; in a patient with a history of DM&#44; who shares another severity factor&#44; COVID-19 infection&#46; Prompt and correct treatment with antifungals and surgical approaches resulted in a disfiguring outcome&#44; but with the preservation of the patient&#39;s life in this serious and fatal disease&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Financial support</span><p id="par0030" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Authors&#39; contributions</span><p id="par0035" class="elsevierStylePara elsevierViewall">Sandy Daniele Munhoz&#58; Design and planning of the study&#59; data collection&#59; analysis and interpretation of data&#59; drafting and editing of the manuscript&#59; obtaining&#44; analyzing&#44; and interpreting data&#59; critical review of important intellectual content&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; critical review of the literature&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Rute Facchini Lellis&#58; Analysis and interpretation of data&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Ana Paula Carvalho Reis&#58; Analysis and interpretation of data&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Gilda Maria Barbaro Del Negro&#58; Obtaining&#44; analyzing and interpreting data&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Maria Gl&#243;ria Teixeira Sousa&#58; Analysis and interpretation of data&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">John Verrinder Veasey&#58; Design and planning of the study&#59; data collection&#59; analysis and interpretation of data&#59; drafting and editing of the manuscript&#59; critical review of important intellectual content&#59; effective participation in research orientation&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; critical review of the literature&#59; approval of the final version of the manuscript&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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Tropical/Infectoparasitary Dermatology
Rhino-orbito-cerebral mucormycosis caused by Rhizopus microsporus var. microsporus in a diabetic patient with COVID-19
Sandy Daniele Munhoza, Rute Facchini Lellisb, Ana Paula Carvalho Reisc, Gilda Maria Barbaro Del Negroc, Maria Glória Teixeira Sousac, John Verrinder Veaseya,d,
Autor para correspondência
johnveasey@uol.com.br

Corresponding author.
a Dermatology Clinic, Hospital da Santa Casa de São Paulo, São Paulo, SP, Brazil
b Pathology Laboratory, Hospital da Santa Casa de São Paulo, São Paulo, SP, Brazil
c Medical Mycology Laboratory ‒ LIM-53, Division of Clinical Dermatology, Faculty of Medicine, Hospital das Clínicas and Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, São Paulo, SP, Brazil
d Medical Sciences College, Santa Casa de São Paulo, São Paulo, SP, Brazil
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and the material was sent for histological examination&#44; which showed coenocytic hyaline hyphae with a 90&#8239;&#176; angle &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; and for fungal culture&#44; which showed growth of <span class="elsevierStyleItalic">Rhizopus sp&#46;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; The colony was sent for identification of the isolate by PCR&#44; and the regions of the internal transcribed spacer &#40;ITS&#41; were amplified using the ITS4 and ITS5 regions of the 5&#46;8S gene of the fungus ribosomal DNA &#40;rDNA&#41;&#44; which identified the agent <span class="elsevierStyleItalic">Rhizopus microsporus var&#46; microsporus</span>&#46; After treatment with liposomal Amphotericin B and compensation of the underlying disease&#44; the patient developed a worsening clinical picture&#44; requiring a second surgical approach with ocular enucleation and extensive surgical debridement&#46; The patient had a good evolution&#44; with progressive improvement&#44; and was discharged after 66 days of hospitalization under outpatient follow-up for aesthetic adjustment&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Mucormycosis is a rare&#44; opportunistic&#44; globally distributed fungal disease whose physiopathology is centered on angioinvasion that leads to tissue necrosis&#46; Among the most often described etiological agents are the coenocytic fungi of the <span class="elsevierStyleItalic">Rhizopus</span> and <span class="elsevierStyleItalic">Mucor</span> genera&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Because it is an ubiquitous and saprophytic fungus&#44; the infection usually occurs in patients with a disease that favors immunosuppression&#44; with DM being the most common one&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> The most frequent clinical form is the rhino-orbito-cerebral type&#44;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;4</span></a> which has a poor prognosis and shows better rates when amphotericin B is associated with extensive surgical excision of the infected tissue&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In a study conducted before the COVID-19 pandemic&#44; 71&#37; of the world&#39;s cases of mucormycosis were reported in India&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In a recent study carried out in the same country&#44; 1&#46;8&#37; of COVID-19 patients developed mucormycosis&#44; of which 76&#46;6&#37; of these co-infected patients were diabetics&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> These rates are not surprising&#44; as India ranks second in the world in absolute numbers of people with DM&#44; which is the main risk factor for mucormycosis&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">SARS-CoV-2 also promotes changes in the host&#44; especially in the severe forms of infection&#44; favoring the development of mucormycosis agents&#46; Among them are the direct damage to pancreatic cells&#44; causing acute DM and ketoacidosis&#44; the use of corticosteroids&#44; which alter glycemic homeostasis and indirectly favor the progression of mycosis&#44; the alteration of iron metabolism leading to an internal environment with high rates of ferritin&#44; a key factor for the development of the fungus&#44; and finally&#44; endothelitis caused directly by the virus&#44; facilitating fungal angioinvasion&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The case described herein maintains the classic line of mucormycosis presentation&#44; the rhino-orbito-cerebral type&#44; in a patient with a history of DM&#44; who shares another severity factor&#44; COVID-19 infection&#46; Prompt and correct treatment with antifungals and surgical approaches resulted in a disfiguring outcome&#44; but with the preservation of the patient&#39;s life in this serious and fatal disease&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Financial support</span><p id="par0030" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Authors&#39; contributions</span><p id="par0035" class="elsevierStylePara elsevierViewall">Sandy Daniele Munhoz&#58; Design and planning of the study&#59; data collection&#59; analysis and interpretation of data&#59; drafting and editing of the manuscript&#59; obtaining&#44; analyzing&#44; and interpreting data&#59; critical review of important intellectual content&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; critical review of the literature&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Rute Facchini Lellis&#58; Analysis and interpretation of data&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Ana Paula Carvalho Reis&#58; Analysis and interpretation of data&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Gilda Maria Barbaro Del Negro&#58; Obtaining&#44; analyzing and interpreting data&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Maria Gl&#243;ria Teixeira Sousa&#58; Analysis and interpretation of data&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">John Verrinder Veasey&#58; Design and planning of the study&#59; data collection&#59; analysis and interpretation of data&#59; drafting and editing of the manuscript&#59; critical review of important intellectual content&#59; effective participation in research orientation&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; critical review of the literature&#59; approval of the final version of the manuscript&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">COVID-19 disease caused by the SARS-CoV-2 coronavirus causes a wide range of clinical manifestations&#44; ranging from mild to severe&#44; with the main ones affecting the respiratory tract&#44; such as pneumonia&#46; In patients with greater severity&#44; the high frequency of bacterial and fungal coinfection stands out&#44; a situation related both to the patient&#39;s pre-existing comorbidities and due to the hospitalization itself&#46; Cases of mucormycosis associated with COVID-19 were highlighted in the lay and scientific media&#44; with the increase in mycosis cases being directly and indirectly attributed to the viral infection&#46; This report describes a case of rhino-orbito-cerebral mucormycosis in a diabetic patient hospitalized for COVID-19&#44; whose diagnosis was confirmed by identifying the agent <span class="elsevierStyleItalic">Rhizopus microsporus var&#46; microsporus</span> through culture for fungi and PCR examination&#46;</p></span>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Histopathological section of a surgical specimen from the patient with rhino-orbito-cerebral mucormycosis showing coenocytic hyphae at &#215;400 magnification&#46; &#40;A&#41;&#44; Hematoxylin &#38; eosin&#46; &#40;B&#41;&#44; PAS staining&#46; &#40;C&#41;&#44; Grocott Gomori staining&#46;</p>"
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