Clinical Features and Mortality of COVID-19-Associated Mucormycosis: A Systematic Review and Meta-Analysis

Abstract

The recent increase of COVID-19-associated mucormycosis (CAM) has been commanding global attention. However, basic epidemiologic characteristics have not firmly been established. In this systematic review and meta-analysis, we sought to determine the clinical manifestations, potential risk factors, and outcomes of CAM. Observational studies reporting CAM were searched with PubMed and EMBASE databases in January 2022. We collected data on comorbidities and treatment for COVID-19, and performed a one-group meta-analysis on the frequency of orbital exenteration procedure and mortality of CAM using a random-effect model. Fifty-one observational studies, including a total of 2,312 patients with proven CAM, were identified. Among the 51 studies, 37 were conducted in India, 8 in Egypt, and 6 in other countries. The most common comorbidity was diabetes mellitus (82%). While 57% required oxygenation, 77% received systemic corticosteroids. Among CAM, 97% were rhino-orbital-cerebral (ROCM), and 2.7% were pulmonary mucormycosis. Usual presentations were headache (54%), periorbital swelling/pain (53%), facial swelling/pain (43%), ophthalmoplegia (42%), proptosis (41%), and nasal discharge/congestion (36%). Regarding the outcomes, orbital exenteration was performed in 17% (95% CI: 12–21%, I 2 = 83%) of the COVID-19-associated ROCM patients. The mortality of CAM was 29% (95% CI; 22–36%, I 2 = 92%). In conclusion, this systematic review and meta-analysis indicated that the most prevalent type of CAM was ROCM, and most CAM patients had diabetes mellitus and received systemic glucocorticoids. Clinicians in the endemic areas should have a high index of suspicion for this invasive fungal complication of COVID-19 when a diabetic patient who received high-dose systemic glucocorticoids developed rhino-orbital symptoms.

SARS-CoV-2 and monkeypox: what is common and what is not in a present pandemic versus a potential one—a neuropsychiatric narrative review

“…Besides dysfunction of the olfactory nerve, other cranial nerves are occasionally affected following SARS-CoV-2 infection and secondary to long-term treatment with steroids in patients who are usually immunocompromised. Such patients might catch rhino-orbito-cerebral mucormycosis with infiltration of the orbital cavity, or nasal sinuses with affection of oculomotor, abducent, trochlear and optic nerves with or without cavernous sinus thrombosis [42,43].…”

Pathogenesis and Pathology of COVID-Associated Mucormycosis: What Is New and Why

“…The clinical form depends on the risk factor and predisposing condition; ROCM is frequently observed in association with uncontrolled DM and DKA, whereas pulmonary involvement is often observed in patients having neutropenia, HSCT, SOT, and hematological malignancies, while gastrointestinal tract (GIT) gets involved more in malnourished individuals and cutaneous form following trauma [ 1 , 10 , 11 ••, 22 ]. The most common type of CAM was ROM or ROCM followed by pulmonary and others (cutaneous, renal, gastrointestinal, disseminated) [ 19 ••, 24 ••, 33 ].…”

“…In a systematic review and meta-analysis, Watanabe et al reported DM as the underlying disease in 82% and administration of corticosteroids in 77% patients of CAM [ 33 ]. In a multi-center epidemiologic study from India, Patel et al reported DM in 60.4% and administration of corticosteroids in 78.7% patients with CAM [ 19 ••].…”

“…The pathophysiology of COVID-19 and the associated secondary infections were described by many authors [ 19 ••, 25 – 30 , 31 •, 32 ]. Several publications described the epidemiology, risk factors, pathogenesis, and outcome of CAM [ 17 , 18 , 19 ••, 20 , 21 •, 23 ••, 24 ••, 33 ].…”

“…Comparison of studies on mucormycosis in pre-COVID times and CAM suggests that diabetic patients with COVID-19, receiving corticosteroids were at great risk of developing CAM [ 10 , 11 ••, 19 ••, 24 ••, 33 ]. The outcome is poor with cerebral or pulmonary involvement and disseminated form of CAM [ 21 •, 24 ••, 33 ]. Table 1 summarizes the demographic details, pre-existing disease, site of involvement, and outcome of pre-COVID-mucormycosis and CAM.…”