|LETTER TO EDITOR
|Year : 2022 | Volume
| Issue : 1 | Page : 40-42
Zinc and mucormycosis—Fact vs myth check
Shibu Sasidharan1, Harpreet S Dhillon2
1 Department of Anaesthesia and Critical Care, Command Hospital, Chandimandir, Haryana, India
2 Department of Psychiatry, Command Hospital, Chandimandir, Haryana, India
|Date of Submission||28-Sep-2021|
|Date of Acceptance||11-Feb-2022|
|Date of Web Publication||18-Apr-2022|
Department of Anaesthesia and Critical Care, Command Hospital, Chandimandir, Haryana
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Sasidharan S, Dhillon HS. Zinc and mucormycosis—Fact vs myth check. Assam J Intern Med 2022;12:40-2
As on June 12, 2021, coronavirus disease 2019 (COVID-19) has totaled 176,104,156 cases with 3,802,165 deaths worldwide. In India, there has been 367,097 deaths so far.
India’s second wave of COVID-19 turned out to be much more deadly than the milder first wave. Large crowds, political rallies, religious gatherings, and compact urban spaces were named as the driving reason for the uncontrolled spread of infection. Researches have also pinned the blame on the new variant of virus, which was first discovered in India (B.1.617.2), which is now assigned the name ‘Delta” by the World Health Organization for this alarming transmission.
Before vaccines were available, there was a raging demand for vitamins C and D and zinc supplements as immunity boosters, which people thought would supercharge their immunity and give them the protection they need to deter the second wave of COVID-19. Zinc and vitamin D apparently helped former US President Donald Trump in his recovery when he was infected in October 2020. The data available on the Internet (pan[info]demic), especially in the face in the pandemic, can be hugely misleading.
Multivitamins’ mechanism of action in the body does build immunity and act as antioxidants, but there is no enough evidence to link its use and prevention of COVID-19. We need solid phase 1 and 2 data, before a phase 3 administration is done in large populations of people. Thus, we should exercise caution in moving forward with the supplementation drive. Although supplements are generally thought of as benign, their excess use is not free from adverse effects.
As the COVID-19 wave ravaged through the country, there emerged a new challenge in the form of mucormycosis (aka black fungus). Mucormycosis (formerly termed zygomycosis) is a lethal but relatively rare fungal infection that is caused by a collection of molds that live throughout the environment called mucormycetes. This disease mainly affects people with comorbidities and those with an obtunded immunity. It usually affects the lungs and sinuses after fungal spores are inhaled from the air we breathe. On May 20, 2021, the Union Health Ministry of India urged the states and union territories to make black fungus a notifiable disease under the Epidemic Diseases Act, 1897.
Over the past few months, India has reported over 28,200 cases of mucormycosis. There are various hypotheses making rounds. Some suggest the use of iron, whereas others blame the failure to use sterile water in oxygen concentrators to this outbreak. Reuse of masks and cannulas is another theory. But does zinc cause/add to the chances of developing mucormycosis?
The fungal cells need zinc for their proper development, even as saprophytes or during the infection process. As a defense mechanism, to halt the growth of pathogen, host animals usually reduce the levels of metals like zinc, making them unavailable to the pathogen. This is called as “nutritional immunity” where the host aggressively interrupts and counters metal uptake by microorganisms.
This is done by various mechanisms:
- There is a pH dependency of zinc uptake. The host’s near-neutral pH lowers zinc solubility and reduces its accessibility for microorganisms.
- Intracellularly, stimulated T cells, macrophages, and dendritic cells decrease their lysosomal zinc content via the expression of the zinc transporter ZIP8, inducing zinc limitation for pathogens in the phagolysosome.
- Stimulated dendritic cells reduce their cytoplasmic zinc concentration by upregulating zinc exporters and downregulating zinc importers.
- By binding to the metallothioneins (MTs) and by sequestering labile zinc, cytokine-activated macrophages restrict the intracellular growth of fungi.
- The host protein calprotectin inhibits bacterial and fungal growth by chelating transition metals, including zinc.,
In human tissues and fluids, the concentration of zinc varies dramatically (body fluids—0.2–8.7 μg/mL, lungs—10 μg/g, liver—83.2 μg/g). Thus, these pathogenic fungi in order to overcome the limits set by the host have developed various operative strategies to uptake zinc. The fungi primarily use the Zinc-regulated, Iron-regulated transporter-like Protein (ZIP) family transporters (eg, Zrt1 and Zrt2) for aiding the zinc transport into the cytoplasm across cellular membranes. Other fungal species also use additional mechanisms to confiscate zinc from host cells and tissues. This is a process very similar to iron chelation. Candida albicans for example secretes Pra1 (its antigenic protein), a zinc-binding protein to scavenge zinc from fungus-invaded tissues. Zrt3 is a ZIP transporter found in the membranes of zincosomes (vacuoles that accumulate zinc) and supplies zinc to the cytoplasm from zincosomes.
This active mechanism of zinc deprivation by mammalian hosts against fungal infection (by the activity of the host zinc transporters or the expression of zinc-binding proteins) is compromised with the excess intake of zinc, which provides the deficient pathogen with the zinc supply it needs to regulate the expression of many proteins, which is required for infection.
Laboratory studies have already proven that zinc chelation can reduce fungal growth in both rich and defined media.
An excess of zinc can however be also toxic for cell. This is because of the fact that zinc does not participate in Fenton chemistry. This is mainly due to a competition with other metals for metal-binding sites in enzymes.
Although scientifically, easy availability of zinc via multivitamin tablets aids molecular mechanisms of pathogenic microorganisms to circumvent host metal restriction and provides a fertile ground for expression; however, for the associating mucormycosis with zinc supplementation, we need more data to ascertain a direct cause–effect relationship.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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