Post COVID-19 Mucormycosis in the Second Wave-Realities, Unc
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There has been an exponential rise in COVID 19 associated mucormycosis (CAM) from nearly every part of the country. Although the true incidence is difficult to estimate given the rampant second COVID 19 surge and the ambiguity of a true denominator, the socioeconomic impact on the population and the health system has been devastating. The sensationalized misnomer of ‘black fungus,’ although taxonomically incorrect, paints a symbolic picture of the diabolical nature of invasive mucormycosis.

Myriad hypotheses have been generated for the inordinate number of cases in our country. Higher fungal spore counts in our tropical climate especially around heaps of garbage, construction of makeshift COVID 19 facilities, contamination of oxygen supplies, respiratory equipment, reused face masks and zinc supplements are some of the theories that have been deliberated upon inconclusively. The most convincing risk factors appear to be unrecognized, uncontrolled diabetes compounded by the indiscriminate use of steroids at high doses for prolonged periods, even in non-hypoxic patients. Such patients have spent most time in the community with all the heavy exposures that go with it. These cases
may be considered as ‘Never in the frying pan, straight into the fire.’

A multicenter study of 187 cases of CAM after the first COVID wave, noted a 2.1-fold increase in the cases of mucormycosis during the peak COVID-19 period as compared to pre-COVID-19 time. Uncontrolled diabetes was noted in 62.7% of cases. COVID-19 was the only risk factor in 32.6% CAM patients among whom 78.7% received glucocorticoid treatment for COVID-19 management. Inappropriate glucocorticoid use was independently associated with late CAM.

Lymphocytopenia with prolonged depletion of T cell subsets is an important feature in COVID-19. This is a known risk factor for opportunistic infections including invasive mucormycosis. Additionally hyperglycemia due to affection of the ?-cells of the pancreas by SARS-CoV-2 may be a contributing factor.

AmB has been grand-fathered into the treatment of invasive fungal infections when there was no other drug available. All subsequent drugs have been compared to this standard. Over the years, AmB deoxycholate has been replaced by lipid formulations, in particular LAmB, in resource rich settings. Although LAmB is an advance in overcoming challenges of toxicity and penetration, the expense and need for intravenous treatment remains an issue. In resource limited settings as also in the current situation, where LAmB is scarcely available, clinicians have to re-learn the best ways to use AmB deoxycholate and certain other products about which adequate data is hard to find.

Better outcomes is of course an unmet clinical need and the question arises whether the new Azoles can meet expectations as initial or step-down treatment for mucormycosis. Some Mucorales species have high minimum inhibitory concentrations (MICs) to AmB or to the newer Azoles indicating a degree of intrinsic resistance, AmB is definitely not a drug of choice for Aspergillus which appears as a coinfection in some patients. Additionally, the penetration of AmB into certain sites eg CNS is suboptimal. The inability to have intravenous (IV) to oral switch, toxicity, cost and prolonged duration of treatment are other shortcomings.

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