Dear Editor,
We read the response letter[1] to our recent paper on COVID-associated mucormycosis
(CAM)[2] with great interest.
According to the letter, we have attributed the CAM surge to the Delta variant (B.1.617.2).
However, our study does not imply so. Rather than a straightforward causal relationship,
our study sought to address and discuss risk factors of CAM during the Delta variant-led
second surge in India. We sincerely request the authors to revisit the discussion
section of our work which addresses potential multidimensional risk factors.
However, our study underlined that the vast majority of mucormycosis cases are that
of unvaccinated people and it is possible that the vaccination has prevented or decreased
the severity of adverse effects causing immune dysregulation and mucormycosis.
Further, there is a possibility that the Delta virus adversely affects the pancreas,[3]
thereby contributing to intense hyperglycaemia and in creating a favourable environment
for the mucormycosis onset. As much as hyperglycaemia and steroid usage need to be
considered as triggering factors, one must, indeed, consider that these two variables
were already present even in the first wave, although no similar outbreak of mucormycosis
occurred at that time. In fact, in India, the routine use of high-dose glucocorticoids
for cancer patients has never resulted in a mucormycosis epidemic. Furthermore, our
study also involved home isolated COVID-19 patients who only took multivitamins and
were not administered steroid or oxygen.
Although industrial oxygen may also be regarded as a contributing factor, its causality
has not been conclusively demonstrated. Actually, it is not known why only some COVID-19
patients were infected and why cases were reported even after cessation of its use.
Besides, there are many patients with CAM for whom external oxygen has never been
necessary for treatment of COVID-19.
Remarkably, the mucormycosis epidemic in India was followed by oxygen crisis, and
many patients suffered with protracted subtle hypoxia throughout recovery, and many
patients with minor symptoms were treated solely by home isolation without any oxygen.
Hypoxia stimulates the endocytosis mechanism in some mucorales species, enabling the
fungus metabolism to shift from carbohydrates to fatty acids, supplying fungi with
extracellular lipids during infection.[4] It is possible that the combination of severe
hyperglycaemia and prolonged hypoxia may have created the perfect conditions leading
to a fast increase in the incidence of mucormycosis.
Finally, the fact that other regions of the world with Delta virus do not have mucormycosis
outbreak may be related to environmental, geographic, and genetic factors (indicated
by high pre-pandemic frequency in India) that may have predisposed immunologically
dysregulated individuals to mucormycosis. However, there have been cases reported
in Brazil, Chile, Honduras, Mexico, Paraguay, the United States, Uruguay, Italy, and
the United Kingdom.[5] In fact, the Pan American Health Organization/World Health
Organization (PAHO/WHO) has advised Member States in the United States to strengthen
health services to prevent CAM-related morbidity and mortality.[5]
Overall, CAM appears to be a multifaceted issue which might have resulted in immunological
dysregulation and predispose individuals to mucormycosis. Until more definite data
is available, prudent administration of steroids, avoidance of long-term hypoxia,
and management of blood glucose levels remain key preventive factors.
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