Novel Cases of Invasive Rhino-Orbital-Cerebral Mucormycosis in 2 Patients Who had Recently Recovered From Coronavirus Disease 2019

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Novel Cases of Invasive Rhino-Orbital-Cerebral Mucormycosis in 2 Patients Who had Recently Recovered From Coronavirus Disease 2019 Elias Keyrouz, BS, Maria Rizk, MD, Mehdi I. Fouani, MD, Haidar Mashlab, MD, Ama Sadaka, MD S evere acute respiratory syndrome coronavirus 2 (SARSCoV-2) mainly affects the lungs but also has other manifestations, including ophthalmic. Limited information exists on fungal coinfections in coronavirus disease 2019 (COVID-19) (1). We report 2 unique cases of invasive orbito-rhino-cerebral mucormycosis presenting 2 weeks after SARS-CoV-2 recovery. We suggest possibly screening patients with COVID-19, especially diabetics, for sinus disease before initiating steroid treatment and raise awareness of this deadly disease. Patient 1 is a 62-year-old man known to have diabetes mellitus type 2 (DM2) who was admitted for fever, altered mental status, bilateral facial palsy, and right facial cellulitis with right eye vision loss and reduced vision in the left eye. He had recovered from COVID-19 two weeks before presentation after hospitalization and treatment with intravenous (IV) dexamethasone 6 mg/day for 10 days, IV ceftriaxone 2 g daily, azithromycin 500 mg daily for 7 days by mouth, subcutaneous insulin, and prophylactic anticoagulation. At home, the patient takes metformin 850 mg by mouth daily. The patient had no diabetic ketoacidosis (DKA) during the current hospitalization, and his polymerase chain reaction (PCR) test for COVID-19 was negative. On examination, there was bilateral ophthalmoplegia and right proptosis with black palate lesions. Vision was no light perception (NLP) in the right eye and hand motion in the left eye. Pupils were bilaterally mid dilated and nonreactive to light. Intraocular pressure was 24 in the right eye and 9 in the left eye. Anterior segment examination of the right eye showed upper eyelid necrosis, conjunctival injection and chemosis, severe corneal edema, Lebanese American University (EK), Gilbert and Rose-Marie Chagoury School of Medicine, Byblos, Lebanon; Ophthalmology Department (MR, AS), Lebanese American University Medical Center-Rizk Hospital, Beirut, Lebanon; Ophthalmology Department (MIF), Ophthalmologist at Beirut Lasik Center, Beirut, Lebanon; and Department of Otorhinolaryngology Head and Neck Surgery (HM), Sheikh Ragheb Harb Hospital, Nabatieh, Lebanon. The authors report no conflicts of interest. Address correspondence to Ama Sadaka, MD, Lebanese American University Medical Center-Rizk Hospital, Zahar Street, Beirut, Lebanon, P.O. Box 11-3288; E-mail: [e-mail] e74 and anterior chamber haze with no view to the fundus. Fundus examination of the left eye showed central retinal artery occlusion. Based on clinical examination and imaging findings (Fig. 1A, B), the patient was diagnosed with invasive rhino-orbito-cerebral mucormycosis and started on IV amphotericin B, meropenem, and vancomycin. Surgical exenteration was considered but was practically impossible because of the extent of the infection and the unstable condition of the patient. Despite all measures, the patient died a few days after. Patient 2 is a 73-year-old man known to have poorly controlled DM2. He presented for right facial cellulitis, facial palsy, and complete ophthalmoplegia 2 weeks after recovering from COVID-19 for which he had received IV steroids for 5 days, IV remdesivir (200-mg loading dose then 100 mg daily for a total of 5 days), azithromycin 500 mg daily by mouth for a total of 5 days, subcutaneous insulin, and prophylactic anticoagulation. At home, the patient takes metformin 850 mg daily by mouth. He was not diagnosed with DKA during this hospitalization, and his PCR test for COVID-19 was negative. Vision was NLP in the right eye and 20/40 in the left eye. No ophthalmic FIG. 1. A. Postcontrast T1 coronal brain MRI. This cut is showing circumferential mucosal thickening in the right maxillary sinus and fat stranding within the right orbit mainly superiorly and laterally. B. Postcontrast T1 axial brain MRI. This cut is showing a filling defect within the right cavernous sinus suggestive of thrombosis (white arrow). Keyrouz et al: J Neuro-Ophthalmol 2023; 43: e74-e75 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence evaluation was performed at that time. Clinical examination, imaging, and biopsies from the nasal mucosa and the maxillary and sphenoid sinuses were suggestive of invasive rhino-orbital-cerebral mucormycosis. The patient was started on IV amphotericin B, meropenem, and vancomycin followed by debridement with resection of the right orbital apex and orbital decompression. He was discharged a month after admission in a stable condition with complete right ophthalmoplegia and same visual acuity. Mucormycosis is a deadly opportunistic fungal infection characterized by infarction of host tissues through angioinvasion. It occurs after inhalation of spores into the paranasal sinuses of a susceptible host, especially diabetics. If not treated promptly with antifungals and surgical debridement, it spreads from the sinuses to the orbit and brain (2). This would cause orbital compartment syndrome and orbital ischemia due to vascular invasion and an expansile process within a closed compartment leading to increased orbital pressure, proptosis, ophthalmoplegia, fixed dilated pupil or afferent pupillary defect, and rapid vision loss (3). The literature shows that fungal coinfections associated with COVID-19 might be missed leading to higher morbidity and mortality rates (1). Only 3 cases of invasive concomitant orbito-rhino-cerebral mucormycosis and COVID-19 have been reported in the literature. Two of them had received steroids as part of their COVID-19 treatment protocol (3–5). To the best of our knowledge, the two patients we describe here are the first reported cases of invasive orbital mucormycosis after recovery from COVID-19. It remains unclear whether it is the vaso-occlusive nature of COVID-19, the angioinvasive nature of mucor, the immunocompromised status of the host, pre-existing DM, or a mix of those factors that Keyrouz et al: J Neuro-Ophthalmol 2023; 43: e74-e75 are responsible for the infection in our patients. We suggest considering an evaluation of the sinuses in patients with COVID, especially diabetics, during and after the administration of steroids, and we highlight the importance of keeping a high level of suspicion for the diagnosis of mucormycosis and initiation of immediate treatment specifically in all the patients with COVID who are admitted and administered on steroids. STATEMENT OF AUTHORSHIP Conception and design: E. Keyrouz, M. Rizk, M. I. Fouani, H. Mashlab, A. Sadaka; Acquisition of data: E. Keyrouz, M. Rizk, M. I. Fouani, H. Mashlab, A. Sadaka; Analysis and interpretation of data: E. Keyrouz, M. Rizk, A. Sadaka. Drafting the manuscript: E. Keyrouz, M. Rizk, A. Sadaka; Revising it for intellectual content: E. Keyrouz, M. Rizk, M. I. Fouani, H. Mashlab, A. Sadaka. Final approval of the completed manuscript: E. Keyrouz, M. Rizk, M. I. Fouani, H. Mashlab, A. Sadaka. REFERENCES 1. Song G, Liang G, Liu W. Fungal Co-infections associated with global COVID-19 pandemic: a clinical and diagnostic perspective from China. Mycopathologia. 2020;185:599–606. 2. Spellberg B, Edwards J Jr, Ibrahim A. Novel perspectives on mucormycosis: pathophysiology, presentation, and management. Clin Microbiol Rev. 2005;18:556–569. 3. Werthman-Ehrenreich A. Mucormycosis with orbital compartment syndrome in a patient with COVID-19. Am J Emerg Med. 2020;42:e5–e8. 4. Mehta S, Pandey A. Rhino-orbital mucormycosis associated with COVID-19. Cureus. 2020;19:e10726. 5. Mekonnen ZK, Ashraf DC, Jankowski T, Grob SR, Vagefi MR, Kersten RC, Simko JP, Winn BJ. Acute invasive rhino-orbital mucormycosis in a patient with COVID-19-associated acute respiratory distress syndrome. Ophthalmic Plast Reconstr Surg. 2020;37:e40–e80. e75 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.