Much More Mucor

Mucor in the New

In several Asian and Middle Eastern countries, mucormycosis cases in post COVID-19 patients are surging.  India has been one of the most affected countries. Likely due to a high prevalence of diabetes mellitus but for ultimately unclear reasons, India had one of the highest pre-pandemic rates of mucormycosis at 80 times the global prevalence.   It is unclear if or how this high prevalence of mucormycosis may be contributing to the surge in CAM cases now. The increased rate in cases of mucormycosis is reported at roughly twofold from a baseline case rate of 14 per 100,000 people.  There are reports of amphotericin B shortages in regions of Asia.  Case series and observational reports from large tertiary centers in India continue to emerge regarding CAM.  Most reports describe the mucormycosis diagnosis occurring in 12-18 days following SARS-CoV-2 diagnosis.  

The pathophysiologic association between COVID-19 and mucormycosis remains unclear though there are several proposed theories.  The foremost and the elephant in the room is inappropriate steroid usage in poorly controlled diabetic patients.  There is some concern that steroids have not been judiciously reserved for the hypoxemic COVID-19 patients, which could accentuate mucor susceptibility in the population of uncontrolled diabetics.  Additionally, COVID-19 associated inflammatory response itself likely leads to glycemic imbalance.  According to available data, more severe COVID-19 cases have a greater association with CAM, and COVID-19 related hypoxemia was an independent predictor of risk for CAM in one reported series.  A theory here is that hypoxemia contributes to end-organ acidosis.  In both cases of glycemic imbalance and local tissue acidosis, a favorable environment for Mucorales molds is created.  Endovascular injury from COVID-19 could also possibly contribute to a more favorable scenario for the angioinvasive hyphae of the mold. Lastly, some authors have theorized as to whether COVID-19 leads to an imbalance of nasal microbiota, promoting Mucorales inoculation.

It is unclear whether infection with SARS-CoV-2 in and of itself has immunomodulatory effects which could predispose a patient to mucormycosis and other secondary infections.  Both Aspergillus and Candida infections have also been reported in association with COVID-19 but typically with much less devastating outcomes. While most reported CAM cases are occurring in uncontrolled diabetic patients and in patients treated with steroids, one epidemiological study regarding CAM cases in India reports 32% of patients having no comorbid conditions other than COVID-19.  

HBOT and Mechanisms

Similar to necrotizing fasciitis and brain abscess where surgery and antimicrobial therapy are first and foremost, the same is true for mucormycosis.  In each of these devastating diagnoses though, HBOT can be considered as an adjunctive therapy where alternative therapies are quite limited.  Mechanisms by which HBOT can benefit fungal CNS infection are as follows:

• Reduction in local hypoxia and acidosis: both are conditions that favor and promote fungal growth.  
• Reduction in local brain edema.  This results from hyperoxic vasoconstriction, reduction in cerebral blood flow, and concurrent tissue oxygenation leading to the cessation of cyclical progression of tissue injury and edema.  
• HBOT has also previously been shown in vitro to enhance neutrophil phagocytosis.
• HBOT can inhibit the growth of anaerobic organisms though most Mucorales sp. can grow and survive in a variety of conditions.