COVID-19: Did India read mucormycosis right?

A month after India reported its first case of mucormycosis in the wake of the second wave of the novel coronavirus disease (COVID-19) pandemic, a host of hypotheses have floated regarding reasons behind the surge in cases of the rare fungal infection.

The country has reported more than 30,000 cases and over 2,000 deaths by mucormycosis so far, according to sources in the Union health ministry. But the real reason behind the spurt continues to be elusive.   

Mycologists — medical professionals who specialise in the study of fungal diseases in humans and animals — too have warned against jumping to any conclusions yet. They added that the disease has been wrongly dubbed as ‘black fungus’.

“The theory that diabetes and overuse of steroids has triggered the fungal infection is well known. All hypotheses, existing research and past studies point out to these two factors. But I am not convinced fully. I strongly believe we are missing out on something,” said Arunaloke Chakrabarti, head, Centre of Advance Research in Medical Mycology, Post Graduate Institute of Medical Education and Research, Chandigarh.

The prevalence of mucormycosis in India was 70 times more than what it was globally — even without the effects of the second wave of COVID-19 — according to a study published March 2021. The study attributed the underlying cause to India having the second-highest cases of diabetes in the world. Diabetes fuels fungal attack. 

Missing links

But what doctors have been seeing lately is unprecedented. Shivaprakash MR, former president of Indian Society of Medical Mycologists, told Down to Earth May 28: “We would earlier see around 100 cases of mucormycosis annually in India. But after the second COVID-19 wave, the number has gone up to 10-15 cases a day. This is the trend we have been witnessing from the last three weeks.” 

But diabetes has been prevalent in India for long, so why the spurt now?

Besides the overuse of steroids (that are given to control falling oxygen saturation levels), COVID-19 infection is also known  to increase glucose levels in blood for the infection causes damage to beta cells that produce insulin.

As insulin levels drop, glucose level goes up. COVID-19 also increases the amount of iron in blood, and iron is a good food for mucor molds.

Chakrabarti, like other microbiologists Down To Earth spoke to, ruled out the use of industrial oxygen as a cause behind the surge in cases, as claimed by several experts. “We have studied this. It doesn’t seem to be the case. Moreover, no mucor was isolated, either in humidifier for oxygen administration or in the oxygen supply pipeline,” he said.

But was there anything particular about the second wave of COVID-19?

Some reports also tried to link the fungal disease with the new Delta (B.1.617.2) variant that originated in India and was behind the second wave. There is no study, however, to support what treating clinicians empirically say in this context.

Epidemiologist and public health expert Chandrakant Lahariya said: “Epidemiologically, the link between the Delta variant and mucormycosis has not been studied. Also, there is something called biological plausibility. Even that does not link the variant to the fungal disease,” he said.

Chakrabarti, who has an experience of over four decades in studying mucormycosis, said he has told researchers, including those from the WHO, that they should not expect “I-have-all-the-answers” from him at this point.

“We have just launched a few multi-center studies and till their results come in, we have to resist the temptation of reaching to any conclusion,” he said.

The studies, among other things, would determine if environmental factors had a role to play in the spurt of these cases. The “transcriptome studies” would try to understand the extent of COVID-19’s impact on people’s immunity and its link with mucormycosis.

Mucormycosis is caused by ‘mucaroles’ order of zygomycetes fungi. The fungi spores are present everywhere — from homes to hospitals. Once an immune-compromised person gets the infection upon inhaling these spores. But no research so far has fully measured the impact or causes of mucormycosis in India following the COVID-19 second wave.

The most recent one is a retrospective observational study involving 16 healthcare centres across India: It collected data for all 295 confirmed mucormycosis cases — those who had COVID-19 as well as those who did not — reported between September 1 and December 31, 2020 (after the first COVID-19 wave and before the second one).

An earlier version of this paper, scheduled for release in September 2021, pointed out to 2.1-fold increase in mucormycosis cases in India during September-December 2020 compared to the corresponding period of 2019. The study attributed most cases to COVID-19.

Diabetes was found to be the underlying cause in 62.7 per cent cases. COVID-19-related hypoxemia (fall in oxygen saturation level) and improper use of glucocorticoid (a class of steroids) were also found to be associated with mucormycosis caused due to COVID-19.

Globally, according to this study, 43 patients of mucormycosis were identified after they got COVID-19 from December 2019-April 2021 (India’s fungal cases increased in May-June). Two-thirds of these cases were found in India. Diabetes, again, was found to be the underlying cause.

What has also intrigued Indian microbiologists is the nomenclature of various fungal infections by their colours (black fungus, white fungus, etc), which has only added to the confusion. Microbiologists say it is patently unscientific to call mucormycosis a ‘black fungus’.

The black fungal infection is caused by an entirely different set of fungus known as ‘dematiaceous’; it has got nothing to do with mucormycosis.  Dematiaceous infection is not as severe as mucormycosis and mainly causes subcutaneous or nail infection. The brain is rarely affected in this disease.

Black, white, yellow fungus: Unscientific nomenclature 

“The global scientific community is laughing at us for what we have done,” said Shivaprakash.

Similarly, what is being dubbed as ‘white fungus’ is an infection caused by another set of microbes called Candida. It is common in many patients who — for reasons besides COVID-19 — have had a prolonged stay in the Intensive Care Unit of hospitals. The environment inside a hospital may cause several infections; Candida infection is among them.

There is hardly anything called ‘yellow fungus’, claimed Shivaprakash. Aspergillus fungi causes this infection, the colour associated with which is more green than yellow. This infection, too, is not particular to COVID-19.

Sarman Singh, director of All India Institute Of Medical Sciences, Bhopal, said some clinicians — who may not have adequate knowledge of emergence of fungal infections — have presented this completely unscientific nomenclature to the media. “The colour of fungus cannot be identified with naked eyes,” he said.

What sets mucormycosis apart from other fungal infections is that it spreads quite fast: four-five cm in a day, mycologists said. If the lesions turn bad and a part of the infected tissue becomes necrotic, it has to be surgically removed. The infection chews up the bones in the surrounding region. If not adequately treated, it spreads to the brain.

(For the record, candida and aspergilus fungal infections don’t require surgical removal of any organ).

Singh added that while the number mucormycosis cases may go down in urban areas, it may spread without adequate diagnosis and treatment in rural areas.

The Union health ministry wrote to all states May 20 that mucormycosis be declared an epidemic. Two days after this letter, the central government stopped giving updates on mucormycosis cases, officially barring an isolated statement from Union health minister Harsh Vardhan on June 7.  What came out since then was unofficial media reports attributed to sources.

(The second story in the two-part series would talk about drug being used for treatment of mucormycosis. An abridged version of this article appeared in DTE print edition 16-30 June, 2021)

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