The "black fungus" through a gray lens
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The COVID-19 pandemic has brought with it a multitude of parallel challenges on a global scale. Our understanding of the pathophysiology and treatment of COVID-19 continues to expand rapidly. In the midst of this pandemic, an ugly new epidemic has raised its head: that of an acute invasive rhino-orbito-cerebral infection by the “black fungus” mucor.

Mucor, a fungus belonging to the Mucorales genus, is found in a variety of ecological environments including soil, dust, decomposing vegetation, as well as excreta of animals like pigeons. Despite this near-ubiquitous existence, clinically significant human infections had been hitherto limited and never on such an unprecedented staggering scale, even in a country like India that already had a relatively high prevalence Many factors may be at play to create this perfect storm. The high prevalence of diabetes, unintended consequences of steroid administration, possible immune effects of the newer variants of the SARS-CoV-n2 virus, and circumstantial evidence around the use of contaminated industrial oxygen may all have a role in this new scourge.

Acute invasive fungal sinusitis (AIFS) in COVID-19-associated mucormycosis (CAM) has been known by many monikers including acute fulminant invasive fungal sinusitis and rhino-orbito-cerebral fungal sinusitis. Acute invasive fungal rhino-sinusitis may be the most appropriate basic descriptor since the middle turbinate is thought to be the epicenter of infection in most cases from where it tends to spread to the rest of the sinuses. Unlike aspergilloma which has a tendency to form a fungal ball or mycetoma, mucor has angioinvasive properties that allow it to rapidly progress across tissue borders without respecting anatomical boundaries. Spreading along neurovascular bundles appears to be the highway to hell for this pathogen, resulting in extensive tissue necrosis with consequent high mortality of 50–80% and high morbidity in those who survive.

A biopsy is essential to confirm the diagnosis. However, imperative to the initial diagnosis and guidance of management is the use of radiological investigations such as MRI and CT. In general, CT is the most commonly used modality for imaging the paranasal sinuses and orbit. However, in mucormycosis, its use is limited as the bony destruction is often insignificant and the soft tissue changes are less apparent on CT. Further, CT may entirely miss findings such as perineural spread along the trigeminal nerve and cavernous sinus involvement – both critical findings with ominous repercussions. The CT findings include a hypoattenuating (hypodense) opacification of the sinuses, usually unilateral, commonly the ethmoid, sphenoid, and maxillary sinuses. This is unlike chronic fungal infections where the sinuses are hyperdense due to the buildup of mineral-rich fungal waste products. CT continues to have a role, however, particularly in resource-poor environments, for patients who are unstable, and for a complimentary evaluation of bony changes.

MRI is an elegant imaging modality that is unsurpassed in its ability to demonstrate abnormalities of the soft tissue as well as bone marrow infiltration. Direct comparisons of MRI and CT in the detection and staging of AIFS have shown a superior sensitivity (86% vs 57–69%) with similar specificity (83% vs. 81%). This disparity of improved sensitivity with similar specificity can be explained by the fact that both modalities look for the same specific hallmark of AIFS, i.e., direct visualization of extra sinus invasion as evidenced by abnormal per sinus soft tissue/edema and loss of perisinus fat planes, for which MRI is far superior. Once extra sinus involvement is present, the diagnosis of invasive sinusitis is apparent, and then staging becomes the next objective. A recently proposed staging system allows for four levels of involvement – nasal cavity, paranasal sinuses and extra sinus involvement, orbital disease, and central nervous system involvement – and serves as a useful guide. Many of these signs are subtle and often become apparent in the light of clinical findings. Gadolinium contrast administration is also necessary to allow delineation of subtle areas of invasion, recognition of necrosis, thrombosis of structures such as the cavernous sinus, and detection of meningitis.

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