First report of COVID-19-associated rhino-orbito-cerebral mucormycosis in pediatric patients with type 1 diabetes mellitus

Abstract

Coronavirus disease 2019 (COVID-19) is a major public health problem worldwide. These patients are at increased risk of developing secondary infections due to a combination of virus- and drug-induced immunosuppression. Recently, several countries have reported an emergence of COVID-19 associated mucormycosis (CAM), particularly among patients with uncontrolled diabetes, with India reporting an alarming increase in rhino-orbito-cerebral mucormycosis (ROCM) in post-COVID cases. Hyperglycemia and diabetic ketoacidosis (DKA) are the major underlying risk factors. So far, case reports and review articles have reported CAM only in adult patients. Here, we describe the first cases of COVID-19-associated ROCM in two pediatric patients with Type 1 diabetes mellitus (DM). Both the cases had asymptomatic infection with SARS-CoV-2 and developed ROCM during the course of treatment of DKA. None of them had exposure to systemic steroids. Imaging findings in both cases revealed involvement of orbit, paranasal sinuses, and brain with cavernous sinus thrombosis. The patients underwent craniotomy with evacuation of abscess. Microbiological and histopathological findings were consistent with the diagnosis of mycormycosis, with fungal culture growing Rhizopus arrhizus . Post-operatively, the patients received liposomal amphotericin B (LAMB) and systemic antibiotics. Retrobulbar injection of LAMB was given in an attempt to halt orbital disease progression. However, it wasn't successful and both of them had to undergo orbital exenteration eventually. ROCM is a rapidly progressive disease and prompt diagnosis with aggressive surgery and timely initiation of antifungal therapy can be life-saving. Physicians should have a high index of suspicion, so as to avoid a delayed diagnosis, particularly in post-COVID patients with uncontrolled diabetes.

Orofacial Mycoses in Coronavirus Disease-2019 (COVID-19): A Systematic Review

“…Of the 108 full texts reviewed, 30 reported cases or case series were included in the present review, and they comprised a total of 292 COVID-19 patients, of whom only 150 had fungal manifestations 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ( Fig. 1 ).…”

“…In addition, a significant age diversity was noted in the cohort, ranging from three COVID-19 positive neonatal cases 15 that developed oral candida infections to adults over 75-years old, with other mycoses. Interestingly, three children aged 11 to 16 years with insulin-dependent Type 1 diabetes were noted with rhino-cerebral mucormycosis 35 , 42 .…”

“…Of the cohort of patients with fungal infections, 92.6% (139/150) had comorbidities, with only a small minority without recorded comorbidity. The predominant comorbidity noted was diabetes mellitus reported in 43.3% (65/150) 21 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 35 , 36 , 37 , 38 , 40 , 41 , 42 together with or without other comorbidities, such as cardiovascular diseases, renal ailments, and liver diseases. A few other patients exhibited an atopic immune condition 14 , asthma 26 , 37 , and mild hypothyroidism 16 , 38 .…”

“…Three mucormycosis patients presenting with oral lesions were simultaneously diagnosed with COVID-19 symptoms 25 , 26 , 27 . In addition, a number of other cases were fortuitous, incidental findings when examined for moderate/severe SARS-CoV-2 infection 42 , 43 , 44 .…”

COVID-19-associated brain abscess caused by Trichosporon dohaense: A case report and review of literature

“…Recent studies indicate that COVID-19 patients are particularly vulnerable to a wide range of opportunistic fungal infections [ 1 , 2 ]. While Aspergillus spp., Candida spp., and Mucormycetes account for majority of these infections, other fungi, such as Fusarium , Cryptococcus , Trichosporon , Histoplasma , and Coccidioides are increasingly being reported [ 3 , 4 ]. It is still unclear whether fungal infections associated with COVID-19 are directly attributable to SARS-CoV-2 or a consequence of underlying factors such as neutropenia, poorly controlled diabetes, structural lung disease and/or other comorbidities, mechanical ventilation, and use of corticosteroids or immunomodulators for the treatment of COVID-19.…”