SARS-CoV-2, Uncontrolled Diabetes and Corticosteroids—An Unholy Trinity in Invasive Fungal Infections of the Maxillofacial Region? A Retrospective, Multi-centric Analysis

Abstract

Objectives Collate and analyse data of maxillofacial/rhino-cerebro-orbital fungal infections reported during the era of the Covid-19 pandemic, with the aim of investigating the common contributing factors leading to such infections and of highlighting the significance of this surge seen in patients infected with SARS-CoV-2. Method This retrospective observational multi-centric study analysed patient data collected from clinicians belonging to different specialties in Bangalore, India. The data included the presentation and management of patients presenting with aggressive maxillofacial and rhino-cerebro-orbital fungal infections and explored the relationship between SARS-CoV-2, corticosteroid administration and uncontrolled diabetes mellitus. Results All 18 patients were Covid positive. Sixteen of the 18 patients received steroids for Covid treatment and 16 patients were diabetic (of whom 15 patients who were diabetics received steroids for Covid-19 treatment). Loss of vision was noted in 12 of the 18 patients and 7 of them underwent orbital exenteration. The fungi noted was mucormycosis in 16 patients, aspergillosis in 1 patient and a mixed fungal infection in 1 patient. Eleven of the patients survived, 6 died and 1 was lost to follow-up. There was a significantly higher incidence of diabetes ( p = 0.03) amongst these cohort of patients who were Covid-19 positive with mucormycosis. A significantly higher number ( p = 0.0013) of patients were administered steroids at some point during the treatment. Conclusion Despite the limited sample size, it is evident that there is a significant increase in the incidence of angioinvasive maxillofacial fungal infections in diabetic patients treated for SARS-CoV-2 with a strong association with corticosteroid administration.

High mortality co-infections of COVID-19 patients: mucormycosis and other fungal infections

“…Six of these patients died, 11 survived and 1 was lost to follow up. Researchers confirmed significantly higher incidence of fungal infections (p = 0.03) amongst diabetic patients and suspect strong association with immunosuppression related to corticosteroid administration 50 .…”

Current Understanding in the Pathophysiology of SARS-CoV-2-Associated Rhino-Orbito-Cerebral Mucormycosis: A Comprehensive Review

“…Apart from the viral-induced hyperglycemia, systemic steroids and antiviral agents used in the management of COVID-19 can also be considered as contributing factors in the worsening of hyperglycemia. There is an increased incidence of mucormycosis infections in diabetic patients treated for COVID-19, who received corticosteroid administration during the course of treatment [ 9 ]. Corticosteroids and immunosuppressive agents are risk factors and prolonged high dose (> 3 weeks) of corticosteroids predisposes an individual to angioinvasive Mucormycosis infection [ 30 ].…”

COVID-19 associated mucormycosis: the urgent need to reconsider the indiscriminate use of immunosuppressive drugs

“…17,22,39,43,44 A recent case series of 18 patients with COVID-19 in India found that 16 developed mucormycosis, six of them with a fatal outcome (>37%). 28 Another series of 10 patients in India identified 10 patients with CAM, suggesting that this condition is more common than expected. 29 Treating physicians should have a high suspicion for CAM in patients with uncontrolled diabetes mellitus and severe COVID-19 presenting with rhinoorbital or rhino-cerebral syndromes.…”

“…The increasing number of recent case series of mucormycosis complicating COVID-19 patients in the United States, 10 – 16 Austria, 17 Brazil, 18 Mexico, 19 Italy, 20 France, 21 Iran, 22 – 24 and India, 25 – 34 raises concerns regarding the misuse of immunosuppressive drugs in patients with COVID-19. Mucormycosis is a neglected mycosis that should be considered in the context of patients with COVID-19, in the same way as COVID-19 associated pulmonary aspergillosis, and it is possibly underreported.…”