When the worst does its best, even the rarest makes it to the commonest. An otherwise rare infection — mucormycosis — has emerged as a serious health crisis amid the ravaging second wave of COVID-19 in India. The ‘black fungus’ infection has hit the headlines after hundreds of cases were reported among recovering and recovered COVID-19 patients across the country. This rare but potentially fatal infection caused by a group of molds called mucormycetes affects the sinuses, the brain and the lungs. It is life-threatening in diabetic and severely immunocompromised individuals, including cancer patients and those people with HIV/AIDS.
Initially found in hospitals in Maharashtra, Gujarat and Delhi, mucormycosis is now being reported from all over the country. Surat, a city of six million in Gujarat, reported 40 cases in the last week of April and out of these, eight lost their eyes within the first 15 days. The health minister of Maharashtra, Rajesh Tope, said on May 11 “there could be over 2,000 mucormycosis patients in the state” and the numbers would “increase for sure” given the rising number of COVID-19 cases.
Meanwhile, the head of AIIMS, Delhi — India’s premier medical institution, Dr Randeep Gulleria, said 23 patients were treated in his institution for the infection and 20 out of them are still COvid positive. “Many states have reported more than 500 cases of mucormycosis as of now and there is an urgent need to control and monitor blood sugar levels among COVID-19 patients,” Gulleria said on May 15, adding that more than 90% of these mucormycosis patients are diabetics.
According to Maharashtra health minister Tope, as many as 111 patients, all COVID-19 survivors, are undergoing treatment for mucormycosis in hospitals in Mumbai and a couple of them have lost their eyesight due to the fungal infection.
While Maharashtra has now decided to create a separate database of cases of mucormycosis to assess its actual spread and how to tackle it, AIIMS chief Dr Randeep Gulleria warned doctors that that the “misuse of steroids” during COVID-19 treatment was a major cause of the infection.
“The data clearly links the current increase in mucormycosis cases with diabetes and steroid intake,” he added.
Referring to a recent meeting that Dr Gulleria had with doctors from Gujarat where 500 cases of the fungal infection have been reported just from government hospitals, he said hospitals in the state have set up special wards for patients with mucormycosis and are now forming combined teams with infectious disease specialists, ENT surgeons, neurosurgeons and plastic surgeons to operate upon these persons.
“Almost all of the mucormycosis patients had taken steroids. More than 90-95% were diabetics. COVID-19 itself leads to lymphopenia, predisposing patients to opportunistic fungal infections,” Guleria said.
He pointed out that steroid intake can lead to a spike in blood sugar levels.
The expert teams in Gujarat are now checking to see if tocilizumab — an immunosuppressant being used to treat COVID-19 by many doctors — also leads to fungal infections.
Dr Yashdeep Gupta, Associate Professor with AIIMS’s department of endocrinology and metabolism, stressed the need for screening patients being admitted to a COVID-19 care facility. This, he pointed out, will help detect undiagnosed hyperglycemia for effective control of diabetes and its consequences during treatment, as well as constant monitoring of sugar levels for diabetic patients and keeping a low threshold for administering insulin.
“Now, we are having two sets of patients: COVID-19 patients with mucormycosis who we are kept in the COVID-19 ward, and those who become COVID-19 negative and continue to have mucormycosis. And the management strategy becomes even more challenging because of these two sets of patients,” said Dr Gulleria.
A fatal fungus
Mucormycosis is an acute and potentially fatal fungal infection. It is caused by members of the fungal group commonly called Mucorales. These fungi produce asexual spores which can infect the oral and nasal cavities through inhalation. These fungi can be easily cultured from the nasal and oral mucosa of healthy humans. In the presence of a normal immune system, these fungal spores are removed by the action of the phagocytic leukocytes.
However if such a defensive mechanism fails, the fungus spore gives out hyphae and begins to grow, leading to fatal consequences. This normally occurs in persons who have uncontrolled diabetes mellitus (particularly in the presence of ketoacidosis), malignancy (such as lymphoma and leukemia), renal failure, AIDS, extensive burn, chronic sinusitis or having advanced rheumatologic disorders. Persons who have done organ transplantation and taking immunosuppressive agents are at the high risk group.
If the leukocytes have less efficacy on destroying the fungal spores, the fungal hyphae will proliferate and invade the vessel walls of the infected region of the human body. This could result in thrombosis, ischemia and necrosis. The infection can spread into the paranasal sinuses and from there it can spread into the orbital and intracranial spaces. This can happen either directly or through the bloodstream, resulting in a pathologic condition called rhino-orbito-cerebral mucormycosis which is the most common type of human mucormycosis.
Other common forms
Other forms of mucormycosis also exist, but they are not as common as rhino-orbito-cerebral mucormycosis. These include the cutaneous, pulmonary, gastrointestinal, and disseminated form of mucormycosis. Though not a common occurrence, mucormycosis of the gastrointestinal tract can also occur as a result of the ingestion of the spores. Though this kind of mucormycosis is with high mortality rate (85%), it is rarely reported in an immune-competent patient.
The symptoms of gastro-intestinal mucormycosis may include fever, nausea, abdominal pain, gastro-intestinal bleeding, and perforation. The endoscopic appearance of gastric mucormycosis is usually a large ulcer with necrosis, eventually presenting an adherent, thick, green exudate. Diagnosis is confirmed by histopathologic identification based on the biopsy of the suspected area during surgery or endoscopy.
Chances of co-infections
According to studies among COVID-19 patients, mucormycosis can be a result of fungal super-imposition or coinfection. As per the researchers, T lymphocytes (CD4 and CD8) are found to be low in severe COVID-19 and the levels of IL-2 R, IL-6, IL-10, and TNF-α are markedly high. However, as part of a case report submitted to the European Journal of Ophthalmology, 24 November 2020, COVID-19 has never been reported as a predisposing factor for rhino-orbital and/or rhino-orbito-cerebral mucormycosis.
The symptoms of rhino-orbito-cerebral mucormycosis include facial pain and paresthesia, headache, periorbital and nasal swelling, inflammation, eyelid drooping, proptosis, external and internal ophthalmoplegia, visual loss, and blackish necrosis of palate and nasal mucosa. The disease usually initiates on the nasal and oral mucosa and then spreads to paranasal sinuses.
It propagates into the orbital space through the lamina papyracea. Vision loss is caused by the involvement of optic nerve or retinal supplying vessels. The intracranial space can be involved directly through the orbital orifices and sinus walls, or through the bloodstream. Cavernous sinus thrombosis can occur as a complication which results in the damage of the cranial nerves.
Problem with the symptoms
As per a dossier published by Centres for Disease Control and Prevention (CDC), symptoms of certain fungal diseases can be similar to those of COVID-19. These include fever, cough, and shortness of breath. Some patients may be having COVID-19 and a fungal infection at the same time. However, according to the CDC, people with severe COVID-19, such as those in an intensive care unit (ICU), are particularly vulnerable to fungal infections such as Aspergillosis or invasive Candidiasis. These fungal co-infections can be associated with severe illness
— with inputs from N S Arunkumar and Agencies
What Can Be Done to Mitigate the Crisis?
Dr. Dinoop K.P., Assistant Professor, Clinical Microbiology, at Sree Chitra Tirunal Institute for Medical Sciences & Technology (SCTIMST), Thiruvananthapuram, and Dr. R. Aravind, Head, Department of Infectious Diseases, Medical College, Thiruvananthapuram, have the following suggestions to manage the current crisis caused by mucormycosis:
1. Adequate sugar control should be achieved in patients who are already diabetic with or without COVID-19, with or without steroid treatment, to reduce the overall incidence.
2. Early identification of the disease should be done via all possible ways by the health staff if the patient is in a hospital. Before a patient leaves the hospital, he/she or the bystanders must be given an awareness about the early symptoms of the disease. Such awareness programmes done can also help those who are at home or quarantine centres.
3. The hygiene level of the hospital must be enhanced. Appropriate use of sterile saline or distilled water for humidifiers in ventilators is mandatory. There should be regular practice of disinfection. These actions can prevent infections having a hospital origin.
4. A judicious use of broad-spectrum antibiotics must be ensured, as this represents another possible risk factor for COVID-19 patients admitted to hospitals.