The rise of mucormycosis in Covid-19 patients in India

The health-care system in India has been unable to cope with the onslaught of wave 2 Covid-19 pandemic. At its peak in early May 2021, over 400,000 cases of Covid-19 were being reported on a daily basis [1], and India found itself unprepared with acute shortage of drugs, vaccines, ventilators, and oxygen [2]. Although Covid cases are currently getting under control, India is now facing a public health emergency of mucormycosis, commonly labeled as ‘black fungus,’ a rare but potentially fatal fungal infection. Mucormycosis is caused by the mucormycetes, a group of molds, with Rhizopus and Mucor as the most common species [3]. As announced by Mr Harsh Vardhan, the former Health Minister of India, there are over 40,000 cases of mucormycosis reported as of 28 June 2021 [4]. Mucormycosis has been declared an epidemic in several Indian states and has been classified as a notifiable disease. Early diagnosis and prompt initiation of treatment is crucial as the condition can progress rapidly with fatal outcome. The treatment for this condition is based on a combination of antifungal medication and aggressive surgical debridement of necrotic tissue if necessary. The recommended anti-fungal drug is Liposomal Amphotericin B on a dose of 5 mg/kg/day. However, acute shortage of Amphotericin B on the one hand and its prohibitive cost to patients and their families on the other is a major challenge.

The etiology of the sudden rise of mucormycosis in India appears to be multifactorial in nature with several hypothesis linking mucormycosis to severe Covid-19 patients who are immune compromised and/or have associated co-morbidities. For example, diabetes, which is a known risk factor for Covid, is also found to be strongly associated with risk of mucormycosis. According to the WHO [5], about 1.5 million deaths were attributed to diabetes globally, and its prevalence is increasing rapidly in low- and middle-income countries. India, home to over 77 million diabetics, has the second highest number of diabetics in the world next to China [6] and that the prevalence of diabetes in India is on the rapid rise [7]. A recent study of about 100 Covid cases with mucormycosis found that almost 80% of these had diabetes [8].

Medical and public health specialists also link the rise of mucormycosis in patients with a history of Covid mostly due to the indiscriminate use of steroids and other broad spectrum antibiotics. For example, steroids, life-saving drugs if judiciously used, could end up harming patients if irrationally used as they are known to suppress immunity on the one hand, and raise blood sugar levels on the other thus contributing to the risk of developing mucormycosis [9]. In addition, experts also associate the rise of mucormycosis to the current dominant variants of SARS infection, namely Delta variant found in India [10]. It may however be noted that the link between the dominant Delta variant and mucormycosis is yet to be established. Moreover, the use of other unproven treatment regimes for Covid like zinc and iron supplements, which aid the fungus to grow by providing the right environment are also linked to the rise. Others have also associated the rise of mucormycosis to prolonged use of ventilators and humidifiers, and unhygienic use of masks. However, a hypothesis that has been underreported by the global medical community but being debated by some experts in India is the use of industrial oxygen cylinders for medical purposes as a potential link to rise in mucormycosis among Covid patients [11,12]. It may be noted that Karnataka state in India has recently authorized a team of microbiologist to analyze the link between mucormycosis cases and the use of industrial oxygen in patients with Covid [13].

Oxygen is used in industries for several purposes including welding, cutting, and other chemical and combustion applications. Given the dire need for oxygen in India, it is not surprising to note that huge quantity of industrial oxygen was diverted for medical use, and the oxygen cylinders used in industries were used to transport the oxygen to hospitals and health facilities. According to the WHO, medical-use oxygen is very different from industrial oxygen in purity and quality, and that the production, storage, and distribution processes involved with industrial oxygen could result in contamination [14]. For example, the industrial oxygen cylinders are inappropriate for medical use as these can be contaminated with impurities as a result of use of unclean equipment, unhygienic storage, and may be prone to micro leaks. Therefore, industrial oxygen cylinders need to be upgraded for medical use by undergoing a process of deep cleaning and disinfection, sealing micro leaks, replacing valves, and ensuring they are free of any contamination before their use for medical purposes. Given the acute shortage of oxygen on one hand, and the time and costs involved with this process on the other, it is likely that implementation of protocols for conversion of industrial oxygen cylinders to medical use at various levels was not adhered to thus enhancing the risks of mucormycosis. This is more so as there is currently no law that can make anyone accountable.

To control the rise in mucormycosis, India needs to act immediately and take measures at various levels. Industrial units that supply oxygen should ensure that the industrial oxygen cylinders are upgraded for medical use. Central Drugs Standard Control Organisation (CDSCO), the regulatory body of medicines and medical devices, which is also responsible for ensuring safety and well-being of patients must be given the specific powers and responsibility for this. Hospitals must seek approval and necessary certification from CDSCO to ensure proper process and protocols for upgradation of industrial oxygen cylinders for medical use have been effectively implemented. Hospitals and health facilities must adhere to general infection prevention and control norms, and maintain necessary hygienic standards. Hospital staff dealing with oxygen delivery-related equipment (ventilators, humidifiers, tubings, and fittings for oxygen supply) including catheters are trained with respect to fumigation and sterilization procedures, and must ensure sterile water is used for the purpose of humidification. To manage the oxygen delivery system and ensure stock levels minimize contamination and wastage, hospitals may need to appoint qualified technical staff trained for this purpose. Doctors must ensure the use of antibiotics and steroids is justified both in terms of its dosage and duration of treatment, and adhere to prescribed guidelines. Indian Medical Council could take the lead in educating its members and taking strict action against those that do not comply. Over-the-counter sale of steroids and antibiotics should be strongly discouraged. Given its rapid spread and fatal outcome, emphasis must be on early diagnosis and prompt treatment of this condition by regular follow-up of Covid-19 patients who may be immuno compromised or with other predisposing factors like diabetes. Accessibility to Amphotericin B both in terms of availability and affordability by making it freely available in government hospitals and health centers should be a priority. General public must be educated, and the use of unproven treatment for Covid must be discouraged. Other low- and middle-income countries too can learn lessons from India and be better prepared in the event of escalation of Covid-19 situation in their countries. There is need to monitor the situation and review the cases of mucormycosis, and that the association of the aforementioned link of mucormycosis to contamination as a result of use of industrial oxygen must be investigated and acted upon.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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