Professor Arunaloke Chakrabarti, President, International Society for Human and Animal Mycology, and Professor and Head, Medical Microbiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh traces the various factors behind mucormycosis suddenly coming into the limelight
For years, fungi were placed on the lowest rung in the hierarchy of pathogens. Fungal diseases did not and still do not get the attention that viral or bacterial diseases do. They were considered a problem only in people who were significantly immunocompromised. However, the sudden emergence of mucormycosis and its deadly progress has brought the fungi into spotlight.
As a medical mycologist, I have spent 36 years studying fungi, and despite my long experience in this field, I have to say that the current unforeseen situation has left me concerned. In a recent multi-centre study, we noted a 2.1-fold rise in mucormycosis cases in India from September to December 2020, when compared to the same months in 2019. Up until 7th June, more than 28,000 mucormycosis cases have been reported from 28 provinces in India. The figure is mind-boggling, as many clinicians in other parts of the world see very few cases in their lifetime.
Mucormycosis is caused by deadly fungal hitchhikers that appear to thrive under conditions created through COVID-19 and its treatment. According to the same study, it has a case-fatality rate of 45.7 per cent at 12 weeks. The impact has been even more severe in India during the second wave.
Mucormycosis in India
Mucormycosis is an aggressive and angio-invasive disease that affects the blood vessels in the body. We know of about 38 different species of ‘mucorales’ fungi that can cause mucormycosis. So far, most cases have been seen in those with uncontrolled diabetes, which is the most important pre-disposing condition in India, while in developed countries, those with blood, lymph nodes and bone marrow-related malignancies; and bone marrow and solid-organ transplant recipients appear to be at a higher risk. Clinically, mucormycosis can occur in multiple forms. Typically, the rhino-orbital-cerebral form which affects the sinuses and eyes is the most common in India, followed by the cutaneous (skin), pulmonary and other forms.
The immune response to mucormycosis
The human immune system is a complex defence system, and contrary to popular understanding, it includes monocytes and neutrophils beyond the T and B cells. However, we are still studying how the immune system responds in the case of COVID-19 and mucormycosis together.
What we do know is that different cells in the immune system play a role in trying to get rid of the mucorales fungi. These include the type of white blood cell known as ‘neutrophils,’ as well as T cells. Natural killer (NK) cells can also damage the string-like part of the fungus known as ‘hyphae’ but do not affect the fungal spores which are largely responsible for the infection. Even platelets, normally known for their ability to aid blood clotting, help to damage the fungal hyphae.
COVID-19-associated mucormycosis
Traditionally, the prevalence of mucormycosis in India has been estimated to be about 70 times higher than the global average. However, those estimates are from before COVID-19. The current spike in the number of mucormycosis cases is being fuelled by four factors: the human host, SARS-CoV-2 treatment and the hospital environment.
- Host Factors: Right from the beginning of the pandemic, we observed that people with diabetes were more likely to get severe COVID-19. Moreover, several cases of new-onset diabetes were also being reported after COVID-19. Unfortunately, uncontrolled high blood sugar levels have a negative impact on the functioning of the immune cells.
- Virus factors: The SARS-CoV-2 virus affects iron metabolism in its host which leads to higher levels of iron in the blood. Iron is essential for the growth of the mucorales fungi and enhances their ability to cause disease (virulence). The virus causes endothelitis (meaning: damage to the small vessels), allowing the mucorales to enter in circulation. The virus also causes immune dysregulation in the host, making it potentially harder to clear the fungal infection.
- Treatment factors: Treatment with steroids has been an essential part of COVID-19 treatment. Unfortunately, steroids can cause hyperglycaemia and impair the functioning of the immune system. Therefore, excessive steroid use for a prolonged period of time causes the patient to become more susceptible to opportunistic infections such as mucormycosis.
- Environment factors: Mucorales are commonly found in different environments such as soil and decaying organic material. In addition, nosocomial mucormycosis has also been reported as these pathogenic fungi have been detected in the air of hospitals in India.
What needs to be done
The judicious use of corticosteroids, along with the careful monitoring of blood sugar levels when a patient with COVID-19 is in the hospital, and use of a mask even at home after getting discharged from a COVID hospital, to avoid exposure to mucorales, and the timely anti-fungal treatment and surgical resection when appropriate, are the crucial measures to stem the rapid increase in mucormycosis cases, and lower the associated mortality rate.
While it may seem like the worst is behind us, the next one to two months will also be crucial. Further, as long as COVID-19 cases are being detected in India, doctors would need to be alert to possible mucormycosis presentation. Some cases may also be diagnosed after discharge, for which reason doctors should advise patients about the early signs of mucormycosis like nasal blockage, one-sided facial pain, black- or brown-coloured nasal discharge, loosening of teeth, etc. In addition, ENTs and general practitioners should be vigilant to pick up mucormycosis cases early.