Abstract
In the past few weeks, India has seen a huge surge in COVID-19 cases. This is possibly due to a new double mutant variant, known as B.1.617. It contains 2 mutations that have been linked to increased transmissibility and an ability to evade immune protection. Along with the surge of COVID-19 cases, a large number of cases of invasive fungal infection, rhino-orbital, or rhinocerebral mucormycosis are being reported in India. Why are so many cases of invasive fungal infection being reported suddenly? Why are there such large numbers being reported from India?
It has been observed that COVID-19 could have a potential diabetogenic effect. 1 New-onset diabetes and complications of preexisting diabetes, including diabetic ketoacidosis, have been observed in COVID-19 patients. The possible mechanism for this is that SARS-CoV-2 binds to ACE2 receptors expressed in pancreatic beta cells, causing pleiotropic alterations of glucose metabolism that could complicate the pathophysiology of preexisting diabetes or lead to new-onset diabetes. 2 Diabetes is a well-known risk factor for mucormycosis and is being reported in more than half the cases of mucormycosis in India. 3 India has the second largest number of adults affected with diabetes mellitus, after China. India has more than 65 million adults with diabetes. 4 Further, there is an underlying higher genetic susceptibility to diabetes in Indians. This could be one of the possible reasons for large number of cases of mucormycosis in India.
COVID-19, in addition to hyperglycemia, also causes dysregulation of iron homeostasis, including iron overload. SARS-CoV-2 attacks hemoglobin causing dissociation of the porphyrins from iron and releasing iron into the circulation 5 . The free iron released into the circulation may cause iron overload leading to oxidative damage of the lungs and other organs. This results in increased uptake and storage of iron in iron-binding proteins, thereby resulting in increased ferritin concentrations. Iron overload may also result in inflammation and immune dysfunction. 6 Iron overload and excess free iron seen in acidemic states are important risk factors for mucormycosis.
As a result of the sudden increase in COVID-19 cases in India, there was over-zealous use of glucocorticoids. Glucocorticoids have no proven benefit in patients who don’t require respiratory support. However, many patients with mild COVID-19 not requiring supplemental oxygen have been treated with glucocorticoids. Corticosteroids suppress the immune system, as well as, raise the blood sugar levels in patients with diabetes and prediabetes. These factors may lead to triggering the cases of mucormycosis. Corticosteroids affect virtually every cell type involved in immune and inflammatory response. They affect the number of mononuclear leukocytes, causing lymphopenia and monocytopenia, as well as suppress several polymorphonuclear leukocyte functions, including phagocytosis. Mucorales, responsible for mucormycosis, possess unique virulence traits that enable the organism to exploit this state of immunosuppression.
Although mucormycosis associated with COVID-19 is not unique to India, emerging data indicate that the extraordinarily high prevalence is multifactorial. The combination of COVID-19, diabetes, and corticosteroids have led to an alarming increase in the number of cases of rhino-orbito-cerebral mucormycosis. These invasive fungal infections if not treated early with antifungal therapy and debridement may be fatal. To prevent it, misuse of steroids must be stopped. Also, blood glucose levels must be closely monitored and controlled.
