A complex interaction of factors, including pre-existing diseases, medical therapy for management of COVID-19 induced complications, the risk of hospital-acquired infectionsand systemic immune alterations due to COVID-19 infection itself, may have been some of the predisposing factors for mucormycosis [2]. A few hypotheses may be proposed as under:

COVID-19 patients have immune dysregulation, with a decrease in number of T-lymphocytes i.e., CD4-Positive and CD8-Positive T-cells, thereby altering the innate immunity of an individual and enhancing the risk of invasive mycosis [2].

SARS-CoV and SARS-CoV-2 belong to the same species; have similar prevalence, clinical and biological characteristics. An increased incidence of fungal infection in SARS patients was noticed (14.8–27%), which was the major cause of death in those patients [3]. Similarly, an incidence of invasive fungal infections of 26.7% was reported by White et al in 135 screened adults with COVID-19 infection. Cases with invasive fungal diseases had an increased mortality (53% vs 31%) [2]. So, it may be hypothesised that due to similar biological behaviour as SARS-CoV, SARS-CoV-2 also predisposes to invasive fungal diseases.

The route of entry of SARS-CoV-2 is mediated through binding with angiotensin-converting enzyme 2 (ACE2) receptors. Nasal and oral mucosal epithelium have shown high expression of these receptors, that may have led to the increased affinity & attachment to these cells [4]. This may explain the symptoms of anosmia, ageusia, oral mucosal ulcerations and necrosis. Tissue necrosis of oro-nasal mucosa may promote mucormycetes, that is a normal commensal and saprophyte, to cause the invasive disease.

SARS-CoV-2 like other coronaviruses including SARS-CoV causes blocking or neutralisation of ACE2 receptors which increases the expression of pro-thrombotic CX3CL1, thus sparking off an increase in local inflammatory mediators, thromboembolic events and tissue necrosis. This in turn may predispose to fulminant fungal infections [5].

Countries like India have a high prevalence rate of type 2 diabetes mellitus (8.9% of adults), which is a well-known risk factor for the disease [2]. COVID-19 may also predispose infected individuals to hyperglycaemia and subsequent fulminant mycosis as described in Figure-1 & Figure-2 [6,7,8].

Corticosteroid therapy is associated with an increased risk of invasive fungal disease. Present guidelines in India recommend intravenous methylprednisolone 0.5-1 mg/kg/day for 3 days in moderate cases and 1-2 mg/kg/day in severe cases of COVID-19. The National Institute of Health recommends the use of dexamethasone (6 mg/day for a maximum of 10 days) in patients who are ventilated or require supplemental oxygen. These guidelines specifically mention the risk of developing a secondary infection [2].

Rawson et al reported the widespread use of broad-spectrum antibiotics, with as many as 72% of patients receiving these drugs, despite any evidence of infection [2]. Use of broad-spectrum antibiotics, may have led to an increase in the number of invasive mycosis super infections.

Luksamijarulkul P et al isolated fungal contaminants from the inside surface of used surgical masks mainly, Aspergillus spp. (37%) & Penicillium spp. (31%) [9]. This suggests that unhygienic practices like continued use of masks/ unwashed cloth masks may be another predisposing factor for fungal as well as bacterial infections.

Antinori S. et al. observed a high incidence of candidemia in patients treated with tocilizumab, which is used to manage cytokine storm in COVID-19 patients [10]. Despite much evidence in the literature, it may be considered as an additional precipitating factor in the pathogenesis of invasive fungal diseases.