Rhino-Orbital-Cerebral Mucormycosis—Another Deadly Complication of COVID-19 Infection

Abstract

SARS-CoV-2, which causes the clinical disease COVID-19, has now affected more than 200 million patients worldwide with close to 5 million deaths. 1 Ophthalmic manifestations of COVID-19 are wide-ranging and present in up to 10% of patients, most commonly as conjunctivitis. 2 The enormous number and high acuity of infected patients have placed significant burdens on health care systems worldwide. The resulting deferral of medical care for other life-threatening conditions such as cancer and heart disease may lead to additional morbidity and mortality.In this issue of JAMA Ophthalmology, Choksi et al 3 join other authors in focusing our attention on another potentially lethal complication of SARS-CoV-2 infection, rhinoorbital-cerebral mucormycosis (ROCM) associated with COVID-19, that is, COVID-19-associated mucormycosis (CAM). Prior to the pandemic, mucormycosis was considered a rare disease, with an incidence of 0.005 to 1.7/million. 4 Fewer than 10 cases are encountered annually at Mayo Clinic Rochester (N. Wengenack, PhD, oral communication, October 15, 2021). The current series, by contrast, includes 73 cases of CAM treated over a 3-month period. The authors' experience confirms the massive increase in ROCM cases in India associated with COVID-19, with more than 15 000 cases as of May 2021. 5 Hematological malignancy, diabetes, pharmacological immunosuppression, high-dose steroid therapy, and HIV infection are well-established risk factors for ROCM. 4 In this study, the main risk factors for CAM were diabetes and steroid use. Three-quarters of patients had diabetes, with more than half with disease characterized as uncontrolled. More than 80% received steroids, either intravenous (IV) or oral, to offset the massive cytokine response driving COVID-19-related pneumonitis and acute respiratory distress syndrome. Supplemental oxygen or ventilatory support was required in 82% of patients. Vaccine information was available for 47 patients, of whom 89% were unvaccinated and none were fully vaccinated.Care for patients with ROCM often involves a multidisciplinary and resource-intensive approach combining surgical debridement by otolaryngologists, neurosurgeons, and orbital surgeons, as well as treatment by specialists in infectious disease, endocrinology, nephrology, laboratory medicine, pharmacology, and pathology. Medical management includes glucose control and administration of IV liposomal amphotericin B, possibly combined with azole-class agents. The daily cost of the latter antifungal medications alone may approach $1000, not including hospital admission costs. Such costs, as well as limited availability of drugs due to pandemicrelated supply chain disruptions, may complicate the delivery of care. The authors and other caregivers in India have

Risk Factors for COVID-19 Associated Mucormycosis: The Ophthalmologist’s Perspective

“…All 38 patients received insulin therapy during hospitalisation. The median (IQR) blood glucose levels in all these patients during hospitalisation was 320 (250.5-375) mg/dl over a median (IQR) time of 11 (7)(8)(9)(10)(11)(12)(13)(14) days. Only 16 (42%) patients achieved blood glucose levels < 200 mg/dl at any point in time.…”

“…In the case of para-orbital spread of mucormycosis, several specific signs such as orbital cellulitis not responding to conventional treatment, orbital apex syndrome, ptosis, ophthalmoplegia, blurring vision or vision loss development, bring the patient or physician to consult an ophthalmologist. Unfortunately, the appearance of such symptoms often attests to an advanced stage of fungal invasion, with unfavourable functional (vision loss, eye removal) or even lethal (brain infection via the orbit fissures) outcomes [ 7 ]. The management of such patients is challenging, urging the need for systemic antifungal treatment combined with surgery [ 8 , 9 ].…”

Neuroimaging Findings in COVID-19 Associated Rhino-Orbital-Cerebral Mucormycosis: A Review

“…Rhino-orbital-cerebral mucormycosis (ROCM) is a potentially fatal angioinvasive secondary fungal infection which has shown a growing trend during the COVID-19 pandemic, currently referred to as COVID-19-associated mucormycosis (CAM). 1 2 In all anatomical sites, tissue invasion and angioinvasion are the trademarks of mucormycosis. 3 4 Central nervous system (CNS) affliction represents one of the most morbid manifestations of mucormycosis and often governs the survival and functional outcome of the patient.…”

“… 4 Prior to the pandemic, ROCM had a reported incidence of 0.005 to 1.7/million, which has massively increased since 2021. 2 The main risk factors found for CAM were diabetes and steroid use. 2 Compared with non-COVID ROCM, patients most affected with CAM were middle-aged, diabetic males with recent COVID-19 infection.…”

“… 2 The main risk factors found for CAM were diabetes and steroid use. 2 Compared with non-COVID ROCM, patients most affected with CAM were middle-aged, diabetic males with recent COVID-19 infection. New-onset upper jaw toothache and loosening of teeth were striking symptoms and neurological manifestations, such as headache, proptosis, vision loss, extraocular movement restriction, cavernous sinus, meningeal, and parenchymal involvement were common in CAM.…”