September 2020 was when microbiologists and infectious disease experts in India first noticed signs of a fungal mold mushrooming as a secondary infection in Covid-19 patients. Caused by a fungus named mucorales, it was a rare infection with a high fatality rate.

Growing rapidly in immunocompromised Covid-19 patients, it was devouring their oral, nasal, and brain cavities – a form called rhinocerebral mucormycosis.

Sixteen hospitals across the country began to study the pattern. Over the next three months, they found a two-fold rise in cases of mucormycosis, commonly known as black fungus, compared to the same period in the previous year.

One of the experts who first noticed the trend, Dr Arunaloke Chakrabarti, head of the microbiology department of the Post Graduate Institute of Medical Education and Research in Chandigarh, started holding video conferences and zoom meetings to alert doctors across India to the infection. “But by the time we could create enough awareness, the second wave [of Covid-19] had hit the country,” he said.

As cases of mucormycosis exploded, on May 19, the health ministry made it a notifiable disease – doctors were bound to report every case to local health authorities. For three months, India saw a shortage of the antifungal drug, Amphotericin B. Till August, over 50,000 mucormycosis cases had been recorded in the country.

Throughout the crisis, there was no clarity on what was causing the fungal epidemic in India. Other countries with heavy Covid-19 caseloads were not witnessing a similar rise in mucormycosis.

Most infectious disease experts agreed that the high incidence of diabetes in the Indian population and the overuse of steroids in Covid-19 care were important risk factors.

But speculation also grew about the possibility of contamination, either by industrial oxygen administered to Covid-19 patients through cylinders in place of piped medical oxygen, or water used in humidifiers attached to a patient’s bed to moisturise the dry gas.

Now, research backs the claims of contamination – but not by oxygen or water. Instead, a study by infectious disease experts, microbiologists and ENT specialists has found a high possibility that fungal spores spread through air-conditioning vents of hospitals in India.

How fungal spores spread

The study, done during the second wave this year, collected samples from oxygen cylinders, storage tanks and air-conditioning vents of 11 tertiary care hospitals where mucormycosis patients were treated.

“We found fungal spores in 11% of samples collected from air-conditioning vents,” said Chakrabarti. “We could directly correlate this with high mucormycosis cases in those hospitals.”

In contrast, no spores were found in samples taken from oxygen cylinders or humidifiers, he said.

“The [fungal] spores can pass through the air conditioning system,” Chakrabarti explained. “Hospitals need to install high efficiency particulate absorbing (HEPA) filters to block them.”

The researchers also found that air shafts and vents cleaned with soap-water reduced the fungal spore count.

The study is yet to be published, which means its findings have not been vetted by other scientists. Chakrabarti said the research will be completed within a month and then sent for peer-review.

What made Indians vulnerable

While popular theories around the spread of fungal spores may have been off the mark, research has strengthened the view that diabetes and overuse of steroids were the underlying factors that made patients in India vulnerable to mucormycosis.

Another ongoing study by 27 hospitals has found diabetes and inappropriate steroid therapy to be the biggest risk factors for mucormycosis. The study has so far analysed 1,500 Covid-19 patients with mucormycosis, comparing them with 3,000 Covid-19 patients without the infection.

“The blood sugar level went up to 700-800 milligrams per decilitre in Covid-19 patients. The normal range is below 120,” said Chakrabarti. “In such patients, the risk of mucormycosis increased.”

Another observational study by 23 hospitals in India, published recently, reported similar findings: 85.2% of Covid-associated mucormycosis patients had diabetes.

The rapid rise of mucormycosis cases in India led to a shortage of Amphotericin B, the drug used to treat patients. Photo: PTI

India vs the world

The global incidence of mucormycosis varies from 0.005 to 1.7 per million population, according to the World Health Organisation. In India, this number, even before the coronavirus pandemic, was 140 per million population, 80 times higher than the global number.

While the incidence of Covid-associated mucormycosis in India is not known, a study done in 16 hospitals in the country in the early months of the coronavirus pandemic found the disease was prevalent among 0.27% in patients managed in hospital wards and 1.6% in patients managed in ICUs.

“We don’t have answers to why other countries did not record so many cases,” said Dr Anu Gupta, associate consultant in microbiology at Fortis Escorts in New Delhi. “Egypt has a similar medical care system as India, but has few mucormycosis cases.”

Even within India, there appear to be regional variations that are hard to explain.

Based on available government data, western India has reported the maximum number of cases of mucormycosis, followed by South, North and eastern India. Maharashtra reported the highest number among all states – 10,325 cases till October 27.

An opportunistic infection

Just like tuberculosis, fungal infections take root when a person’s immunity drops. Patients with cancer, HIV and those on a high dose of steroids have always been at higher risk of secondary infection.

“Fungi are ubiquitous. They are everywhere,” said Dr Sujata Baveja, retired head of microbiology in Sion hospital, Mumbai. “Leave bread outside for two days and you will find fungal growth.”

Mucorales enter through the nose, mouth or a break in the skin. Once they invade the blood vessels, they multiply rapidly, blocking blood supply. Necrosis, or lack of blood supply, turns a human tissue black, hence the name ‘black fungus’. “The fungus itself is not black in colour,” said Baveja.

What clinicians have so far understood is that Covid-19 affects the pancreas, an organ that produces insulin to maintain blood sugar level in the body. The inability of the pancreas to control sugar levels leads to diabetes in several Covid-19 patients. Diabetes also suppresses immunity. Mucormycosis, an opportunistic infection, attacks then.

To make matters worse, the Covid-19 virus can derange lung and organ functions and cause inflammation. To control the inflammation, steroids are used. “It is a double edged sword. Steroids will suppress the immune system and control swelling, providing a temporary solution at that time, but it will predispose your body to many other infections,” Baveja explained.

More cases from hospitals that overused steroids

Kokilaben Dhirubhai Ambani hospital, one of the 16 centres that studied a rise in fungal infection during the first Covid-19 wave between September to December 2020, analysed 25 of its hospitalised mucormycosis patients.

All of them were administered steroids, and in 13 patients, the steroid doses exceeded the standard limits. Sixteen patients had diabetes, and 21 required oxygen support for Covid-19 treatment. They were mostly sick for a month and admitted in intensive care units.

At least 23 out of 25 patients had first sought treatment in a smaller hospital, and “were given steroids when not required”, said Dr Tanu Singhal, infectious disease specialist in the Ambani hospital.

Dr Om Srivastava, an infectious disease expert with HN Reliance hospital and a member of the Maharashtra Covid-19 Task force, said the accepted dose of dexamethasone, a commonly used steroid, is 6 mg once or twice a day. “But when we conducted the death review of Covid-19 patients, we found that dexamethasone had been administered five to six times a day. This will completely wipe out a patient’s T-cell population,” Srivastava said. Integral to the immune system, T-cells help in the secretion of antibodies to combat a virus and infected cells.

Panic driven by oxygen shortage during the second wave led to an overuse of steroids, several experts told In some cases, patients took steroids at home for over 10 days, without a doctor’s prescription. Dr Renuka Bradoo, head of the ENT department at Sion hospital, said steroid use was aggressive during the second wave compared to the first one.

Changes in Infection control practices

A silver lining in this year’s mucormycosis epidemic, doctors said, was that the fatality rate was lower compared to pre-pandemic times. “Before the pandemic we used to see 40-50% death rate in mucormycosis cases. The fatality rate right now is 13%,” said Dr Avinash Supe, who heads the Covid-19 death audit committee in Maharashtra. “Perhaps faster diagnosis due to better awareness helped provide early treatment.”

Another positive fallout of the crisis, doctors said, was that it put the spotlight on the need for better infection control in Indian hospitals.

Seven Hills hospital, a dedicated Covid-19 facility in Mumbai, for instance, set up an infection control committee in April. The ward boys were using tap water to humidify oxygen used for patients. Left unchanged over two days, the water could become a breeding ground for fungal spores. Recognising the danger, the hospital replaced tap water with distilled water, said Dr Sridevi Chaitanya, member of the committee.

“We started taking samples from the ICU and wards to check for fungal growth. We did not find any,” she said. “But we knew mucorales were in the air. So we asked staff to regularly clean air conditioning vents.”

The hospital has also begun regular cleaning of respiratory care devices, ventilators, and oxygen pipelines, she added.

At a larger level, doctors hope that the crisis would spur more research into fungal infections. “There is a lack of investment in the diagnostics and research of fungal infections,” said Dr Chakrabarti, from PGIMER, Chandigarh, adding that there are only seven referral labs in India that are equipped with all diagnostics requirements for microbiology.

Consulted by the Centre during the fungal epidemic, the microbiologist said he had advised the government to set up microbiology facilities starting at primary health centre level. “The Indian Council of Medical Research is developing a referral lab in each state. The idea is to slowly develop a facility in each medical college,” he said.

This reporting was supported by a grant from the Thakur Family Foundation. Thakur Family Foundation has not exercised any editorial control over the contents of this article.