Mucormycosis: A potential head and neck problem in COVID‐19 patients

Mucormycosis is a rare fatal fungal infection that affects the nose and paranasal sinuses and may even extend to the orbit and the brain. The rhino-orbital-cerebral mucormycosis (ROCM) is the commonest form of Mucorales infection. The infection is usually transmitted by inhalation and causes tissue necrosis by angioinvasion and thrombosis. The disease has a rapid course causing ischemia and gangrene of the affected tissue, and it mainly affects immunocompromised patients. Before the pandemic of coronavirus disease 2019 (COVID-19), diagnosis of the disease was limited to individuals with low immunity such as patients with uncontrolled diabetes, end-stage renal diseases, hematologic malignancies, and/or organ transplantation. After the COVID-19 outbreak, many case reports of COVID-19-associated mucormycosis (CAM) have been published. The incidence of the disease is estimated to vary from 0.005 to 1.7 per million population worldwide in the pre-COVID-19 era, with special high incidence in India, which is about 0.14 per 1000 population. Pal et al. described 10 CAM patients along 1.5 months in their institute, and they stated that the prevalence of the disease has risen more than twofold in India during the COVID-19 pandemic. Also, Ravani et al. detected a dramatic increase in the number of patients recently diagnosed with ROCM at their Indian ophthalmology center compared with the pre-COVID-19 era. The Indian government declared mucormycosis as an outbreak in May 2021. Indeed, White et al. reported an incidence of invasive fungal infection of 26.7% among hospitalized COVID-19 patients. In our university hospital, which is the largest tertiary referral center in our country, many CAM patients have been diagnosed recently. In the first 6 months of this year (2021), 16 patients were diagnosed to have ROCM, which is double the number seen in the same period of the previous year. All of them were recovered COVID-19 diabetic patients, and corticosteroids were included in their treatment protocol. Corticosteroids are usually used in the treatment of severe COVID-19 to reduce mortality, especially in hypoxic patients. Unfortunately, it has immunosuppressive and diabetogenic effects that may increase the risk of developing CAM. In many studies, most reported CAM patients were diabetics, and corticosteroids were used for their treatment. Before the COVID19 pandemic, the use of corticosteroids has been identified as a risk factor for mucormycosis. Skiada et al. found that 46% of their patients were on corticosteroids 1 month before developing mucormycosis. Mucormycosis has even been detected in some COVID-19 patients treated with corticosteroids in the absence of the traditional risk factors. COVID-19 could affect the cell-mediated immunity by decreasing the T lymphocytes, especially CD4+ and CD8+ cells. However, many risk factors in severe COVID-19 patients may predispose to the occurrence of invasive fungal infection. Decreased lymphocytic count is a feature in most COVID-19 patients. Mucorales-specific T cells (CD4+ and CD8+) secrete cytokines-like interleukin (IL)-4, IL-10, IL-17, and interferon gamma, which destroy fungal hyphae, and patients with mucormycosis show high levels of those specific T cells, so COVID-19 patients who already have lymphopenia might have a worse disease course than non-COVID-19 patients if they developed mucormycosis. A patient with ROCM is usually presented with offensive black crusty nasal discharge, facial pain, numbness, headache, blurred vision, ptosis, and/or proptosis. Without early diagnosis and treatment, visual loss and/or brain infarction and even death could be the end result of the disease. Nasal examination usually shows black necrotic tissue in the nose and sinuses with possible orbital and/or brain involvement, and similar black tissue necrosis is often seen on the hard palate. Computed tomography imaging is usually essential in the diagnosis, and it shows bone destruction, and also, MRI could reveal brain infarction. Once diagnosis is suspected, a biopsy is taken routinely for direct microscopic examination and culture. Real-time polymerase chain reaction may sometimes be required to accurately detect fungi. Mucormycosis is usually treated with a combined approach: medical and surgical therapy. Control of diabetes is the most important step, with systemic antifungal medications such as amphotericin B (preferable to be liposomal type, to avoid nephrotoxicity) that should be given as early as possible. However, surgical debridement of the necrotic tissue using nasal endoscopy is performed in line with the medical treatment. During debridement, it is crucial to clean the margins to stop the spread of fungal infection. The impact of COVID-19 on mucormycosis is still not fully understood. Several reports indicated a potential increased risk of developing mucormycosis in COVID-19 patients. John et al. reported that 94% of their CAM patients were diabetics. Severe acute respiratory Received: 16 July 2021 Revised: 28 November 2021 Accepted: 28 December 2021