Mucormycosis (MM), also referred to as Zygomycosis or the ‘Black Fungus’ is an uncommon yet significant medical condition in the New World. In India, MM assumes importance as an angio-invasive infection of severe nature, primarily associated with certain diseases such as diabetes, tuberculosis, autoimmune disorders, and various types of cancers. It acts as a secondary infection that can result in detrimental outbreaks, impacting vital organs of the body leading to significant morbidity and mortality (Nagesh 2021; Nagey 1999; Richardson and Lass-Florl 2008). MM was first documented in India in 1963 by Balasubrahmanya and Chaudhuri (1963), in form of a case of pulmonary mucormycosis. However, the disease had been described in humans as early as 1885 by Platauf (1885) in his exemplary work ‘Mycosis Mucorina’. In India, Chakrabarti et al. (2001; 2006; 2009) have conducted extensive MM case control studies beginning with 1990. Since then, MM has been viewed in relation to age, occupation, gender, comorbidities of the affected individuals.
The causal pathogen of this fungal infection belongs to the fungal order mucorales, which are common environmental saprobes found ubiquitously in various substrata such as soil, and decomposing organic matter (Mahalaxmi et al. 2021; Bhat et al. 2021; Dogra et al. 2022). It is known to thrive in hot and humid temperatures, especially in tropical climates. Fungal spores from this group have also been identified in the nasal microflora of healthy individuals as commensals. These spores might become pathogenic in immunocompromised individuals leading to fungal infections (Pasrija and Naime 2022). Despite such ubiquitous occurrence of Mucorales members, MM has been considered a rare disease primarily affecting individuals with underlying conditions that render the body susceptible to fungal infection and its subsequent spread to vital organs (Rootman et al. 1988).
Individuals with compromised immune systems, which can be attributed to various factors including diabetes, cancer, organ transplantation, long term corticosteroid medication or excessive steroid intake (as seen during Covid-19 management), severe burns, HIV, hemochromatosis/iron overload (excessive absorption and accumulation of iron in body), neutropenia (abnormally low neutrophils levels due to factors like chemotherapy, autoimmune disorders, viral infections, bone marrow disorders), malnutrition, hematologic malignancies, old age, or any other condition weakening the immune system, constitute the most vulnerable group susceptible to MM (Dogra et al. 2022; Gonzalez et al. 1997; Petrikkos et al. 2012).
Generally, the incidences of MM have been linked to war casualties, and natural disasters such as volcanic eruptions, tsunamis, and severe burn injuries. However, the most recent and significant impact of MM on humanity has been observed during the Covid-19 outbreak, particularly the second wave that severely affected Indian subcontinent (Walsh et al. 2019; Fanfair et al. 2012; Singh et al. 2021). Additionally, the most prevalent and notorious condition associated with MM in the Indian subcontinent has been Diabetes mellitus (DM) and its poor management. DM has been a prominent risk factor or comorbid condition in a majority of secondary fungal infection cases, contributing to a global 46% mortality rate in MM patients (Prakash and Chakrabarti 2019; Jeong et al. 2019).
Recently, MM has emerged as an infection closely associated with Covid-19, particularly prominent in India. Although instances have also been reported in other countries, including Mexico, Chile, Brazil, USA, Austria, Italy, France, UK, and Iran, resulting in a global epidemic outbreak during 2021. India reported the highest number of mucormycosis cases with Maharashtra and Gujarat standing out with the highest number of CAM cases among the Indian states (Singh et al. 2021; Garcia-Carnero and Mora-Montes 2022). Interestingly, even before the Covid-19 pandemic, India had a higher incidence of MM compared to other countries, primarily due the country’s larger diabetic population (Satish et al. 2021; John et al. 2021). The misuse of steroid medications employed to treat Covid-19 triggered a condition of hyperglycaemia (new-onset of diabetes) which was predominantly held responsible for escalation of CAM cases (Satish et al. 2021; John et al. 2021; Spellberg et al. 2005). This combined with acidosis and elevated blood sugar levels, impairs the ability of neutrophils to efficiently perform phagocytosis, further compromising the immune system (Spellberg et al. 2005). Moreover, the presence of excess free iron in the form of elevated ferritin levels, along with ketoacidosis, hypoxia, and immunosuppression in the affected individuals as well as prolonged stays in intensive care units, added to the complexity of the situation (Satish et al. 2021; John et al. 2021; Spellberg et al. 2005; Pasrija and Naime 2021; Prakash and Chakrabarti 2021; Divakar 2021).
In the present study, the focus of the research analysis centres around understanding MM as a condition linked to a primary or pre-existing disease and any potential correlation thereof. For this, MM case-control studies documented in India were categorized into two time periods; the period before the Covid-19 outbreak, and the other during the recent pandemic, where Covid-19 has been considered as a novel factor linked to MM, hence known as Covid-19 associated mucormycosis or CAM (Singh et al. 2023). A comprehensive collation and analysis of case-control studies from India during these two phases has been done in the present study to unravel the underlying trends, specifically, the association between MM and Covid-19.