key: cord-0700681-uclkxgtq authors: Rodrigues, Mariana Gonçalves; Sekiguchi, William Kazunori; Gonçalves, Sérgio; Casal, Yuri Reis; Frassetto, Fernando Pereira; da Silva, Vinicius Trindade Gomes; Santo, Marcelo Prudente do Espírito; Magri, Marcello Mihailenko Chaves title: Loss of an eye to mucormycosis following corticosteroid therapy for COVID-19 date: 2021-12-20 journal: Autopsy & case reports DOI: 10.4322/acr.2021.345 sha: 16f1893bbc81e5d1902bb1b9b980074ae028d753 doc_id: 700681 cord_uid: uclkxgtq Mucormycosis is a rare, sometimes severe fungal infection that has emerged as a possible complication of COVID-19. We report a case of a non-diabetic, apparently immunocompetent patient diagnosed with rhino-orbital-cerebral mucormycosis shortly after COVID-19 treatment with dexamethasone. The patient received optimized systemic antifungal therapy and extensive surgical treatment. So far, four months after the last hospital discharge, the patient has been in good general condition. This case is a dramatic reminder that beneficial corticosteroid therapy in general inevitably carries a risk of opportunistic infection, and corticosteroid therapy for COVID-19 risks orbital-rhinocerebral mucormycosis that clinicians should watch for with vigilance. Mucormycosis is the infection caused by fungi of the phylum Mucoromycota, order Mucorales. Mucorales fungi are ubiquitous and rarely cause infection in healthy patients. The common underlying diseases in mucormycosis include diabetes mellitus, hematological malignancies, solid organ tumor, hematopoietic stem cell and solid organ transplants, corticosteroid therapy, and neutropenia. 1 Mucormycosis' diagnosis depends on a high index of suspicion due to its rarity outside endemic regions. In this setting, imaging tests and laboratory investigations are essential. Histopathologically, the hyphae are non or pauci-septated and appear ribbon-like with an irregular branching pattern. 1 During the COVID-19 pandemic, systemic fungal infections are causing concern. 2 Most patients reported with COVID-19-associated mucormycosis had diabetes, but there are other possible risk factors in the pandemic context, such as corticosteroids use during moderate and severe forms of COVID-19 treatment. 3 We report a case of a previously healthy patient diagnosed with rhino-orbital-cerebral mucormycosis shortly after COVID-19 treatment. A 39-year-old female patient had flu-like symptoms and was diagnosed with COVID-19 by polymerase chain reaction of the oro/nasopharyngeal secretion. She had no diabetes mellitus history (HbA1c 5,5% in the admission) nor other illness. She was considered immunocompetent (Table 1 shows laboratory investigation towards the patient's immunological status). The patient evolved with dyspnea and hypoxemia, requiring hospitalization and oxygen supplementation. According to a local protocol for COVID-19 treatment, she received dexamethasone (8 mg/day for 5 days), ivermectin, rivaroxaban and azithromycin. Fifteen days later, she had severe pain, edema, and redness over the left eye. Within hours, this condition evolved to a transitory loss of consciousness episode and sphincter release, which motivated a new hospitalization. At hospital admission, the patient had left amaurosis. Periorbital cellulitis and rhinosinusitis (left maxillary, ethmoid and sphenoid sinuses) were identified by imaging exams. She underwent endoscopic endonasal sinusectomy five days later, and received piperacillin/ tazobactam and amikacin for eleven days. Fifteen days after hospital discharge, she presented spontaneous drainage of a left upper eyelid abscess, treated with clindamycin. Two weeks later, she underwent a new sinusectomy, which still found necrotic tissue. The patient received ciprofloxacin, vancomycin, and amphotericin for 7 days. Three weeks after the sinusectomy, the patient was admitted to the emergency room of a tertiary care center with total paralysis on the left eye, fixed mydriasis, ptos, and amaurosis, compatible with orbital apex syndrome ( Figure 1 ). Orbits and paranasal sinuses imaging exams showed findings consistent with invasive inflammatory disease, with orbital involvement on the left (Figure 2A, 2B) . Four days after the last admission, she underwent a second sinusectomy. The material collected in the procedure confirmed the presence of hyphae, and morphological findings were consistent with Mucor spp by histological methods (Grocott histochemical method and Acid-Schiff histochemical method). Prior to this histopathological analysis, the patient had been treated with voriconazole (200 to 300 mg, 4 mg/kg, adjusted according to the serum level) for ten days, which was replaced by liposomal amphotericin at a dose of 7.5 mg/kg/day. After one week, Isavuconazole 200 mg/daily added was added because of lack of clinical improvement. The magnetic resonance imaging (MRI) showed intracranial involvement signs (Figure 3) . One month after the introduction of antifungal therapy, the control MRI showed an increase in frontal lobes involvement. A surgical approach was indicated for debridement. In a preoperative arterial occlusion test, left internal carotid thrombosis was diagnosed. The Head and Neck Surgery and Neurosurgery teams undertook maxillectomy, ethmoidectomy, sphenoidectomy, orbit exenteration and exploration and debridement of the cavernous sinus on the left (Figure 4) . The histological examination confirmed the presence of mucor hyphae in the surgical specimen ( Figure 5 ). During the postoperative period, she presented a cerebrospinal fluid fistula that was treated with acetazolamide and external lumbar cerebrospinal fluid drainage for 5 days. The patient was discharged from the intensive care unit on the twentieth postoperative day and had continued her treatment with liposomal amphotericin (achieving 9 mg/kg/day due to patient's weight loss) for another six weeks and isavuconazole as long maintenance therapy. At the end of this report, the patient was in good general condition (Figure 6 ). COVID-19-associated mucormycosis has been reported worldwide, especially in India. 4 In a review conducted by John et al., 4 41 cases of patients with COVID-19-associated mucormycosis were identified. Among the studied cases, 94% involved diabetic patients. Eighty-eight percent of them received systemic corticosteroids, and 82.9% had a cranial presentation. Unlike most patients reported worldwide, our patient had no previous known immune compromise and was non-diabetic. However, like the other described cases, she received a low dose of corticosteroid treatment for COVID-19, and her clinical presentation was rhino-orbital-cerebral. In an Indian multicenter retrospective study composed of 187 COVID-19-associated mucormycosis cases, Patel et al. 3 found that inappropriate glucocorticoid use (dexamethasone-equivalent doses >6 mg/day for >10 days) was independently associated with late COVID-19-associated mucormycosis (when mucormycosis diagnosis occurred ≥8 days after COVID-19 diagnosis). Pasero et al. 5 discussed whether Sars-Cov-2 itself could be a predisposing factor to immunosuppression and its consequent opportunistic infections. The tendency towards ketoacidosis, corticosteroid use, changes in iron metabolism and damage to the endothelium are possible COVID-19's conditions that could be associated with mucormycosis. 4 Except for dexamethasone therapy, no other evident predisposing factors were identified in the case described herein. The patient reported here received optimized systemic antifungal therapy and extensive surgical treatment. So far, four months after the last hospital discharge, the patient has been in good general condition. We report the case of a non-diabetic, apparently previous immunocompetent patient with an extensive mucormycosis after COVID-19 infection treated with a short-term and low -dose of dexamethasone. More research is needed to understand the role of SARS-CoV-2 infection in the Mucormycosis' development. Furthermore, it is important to emphasize the rational use of corticosteroids. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium Rising incidence of mucormycosis in patients with COVID-19: another challenge for India amidst the second wave? Multicenter epidemiologic study of coronavirus disease-associated mucormycosis When uncontrolled diabetes mellitus and severe COVID-19 converge: the perfect storm for mucormycosis A challenging complication following SARS-CoV-2 infection: a case of pulmonary mucormycosis This study carried out at the Hospital das Clínicas The authors thank Vitor Ciampone Arcieri, Nathália Maria Lopes Cordeiro, Yasmin Laryssa Moura Guimarães, Dorival de Carlucci Junior, Vitor Nagai Yamaki, Marcelo Nobrega Litvoc and Luiz Paulo Kowalski for support. Authors' contributions: Mariana Gonçalves Rodrigues was responsible for data collection, case review and manuscript writing. William Kazunori Sekiguchi was responsible for data collection, data analysis and manuscript review. Sérgio Gonçalves was responsible for the study design, data analysis and manuscript review. Yuri Reis Casal was responsible for data collection and manuscript review. Fernando Pereira Frassetto was responsible for and manuscript review. Vinicius Trindade Gomes da Silva was responsible for manuscript review. Marcelo Prudente do Espírito Santo was responsible for manuscript review. Marcello Mihailenko Chaves Magri was responsible for data analysis and manuscript review.