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Table of Contents
Year : 2021  |  Volume : 9  |  Issue : 3  |  Page : 86-89

The nexus between mucormycosis and COVID-19: A review

1 Department of Oral & Maxillofacial Surgery, Vyas Dental College and Hospital, Jodhpur, Rajasthan, India
2 Department of Oral Medicine Diagnosis and Radiology, Vyas Dental College and Hospital, Jodhpur, Rajasthan, India

Date of Submission18-Jun-2021
Date of Acceptance21-Jul-2021
Date of Web Publication27-Sep-2021

Correspondence Address:
Dr. Sugandha Arya
Department of Oral Medicine Diagnosis and Radiology, Vyas Dental College and Hospital, Jodhpur, Rajasthan.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/INJO.INJO_22_21

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Mucormycosis is a disease of the diseased. Infection arises through inhalation of spores, contamination of the traumatized tissue, ingestion, and direct inoculation. High incidence of mucormycosis is seen in uncontrolled diabetic or immuno-compromised patients. Recently, its appearance has been linked with the COVID-19-affected individuals who are being treated by excess steroids or on other immunosuppressants and those with history of systemic disease. Therefore, for successful management, excessive steroids and immunosuppressive drugs should be avoided in mild cases of COVID-19.

Keywords: COVID-19, immunosuppressants, mucormycosis, rhinocerebral, rhinomaxillary, rhinoorbital

How to cite this article:
Raju SK, Kurdekar RS, Prakash V J, Vyas A, Arya S. The nexus between mucormycosis and COVID-19: A review. Int J Oral Care Res 2021;9:86-9

How to cite this URL:
Raju SK, Kurdekar RS, Prakash V J, Vyas A, Arya S. The nexus between mucormycosis and COVID-19: A review. Int J Oral Care Res [serial online] 2021 [cited 2022 May 25];9:86-9. Available from: https://www.ijocr.org/text.asp?2021/9/3/86/326822

  Introduction Top

Mucormycosis (black fungus) is an emerging angioinvasive infection caused by the ubiquitous filamentous fungi belonging to the class of Zygomycetes.[1],[2] It is a life-threatening, opportunistic, and fulminant fungal infection.[3],[4],[5] Baker, an American pathologist, coined the term mucormycosis. Paltauf, the German pathologist, reported the first case of mucormycosis in 1885 and described it as Mycosis Mucorina.[6]

  Epidemiology Top

The prevalence of mucormycosis in India is reported to be approximately 0.14 cases per 1000 population, which is about 80 times the prevalence reported in other developed countries.[7]

  Pathophysiology Top

Mucor is a saprophytic aerobic fungus; its spores exist widely in nature and are spread in soil, air, food, and decaying organic material.[8] Because of its associated low virulence potential, it may occur in the nasal mucosa of healthy people as a commensal. It can survive in vitro for 2–5 days.[8] If the patient becomes immunosuppressed, this fungus may germinate within the par nasal sinuses and spread intracranially or to other nearby structures such as the orbit. Infection arises by inhalation of spores that get deposited in pulmonary alveoli.[9] Their germination is favored by low oxygen, high glucose, acidic medium, and high iron levels. It also spreads via ingestion or contamination of traumatized mucosa like ulcer or extraction socket by fungal spores. The hallmarks of disease caused by these organisms are angioinvasion, thrombosis, ischemia, and necrosis of involved hard and soft tissue.[10],[11]

  Risk Factors Top

Risk factors include uncontrolled diabetes mellitus (DM), especially ketoacidosis, steroid use, extremes of age, blood dyscrasias, neutropenia, especially with hematological malignancy, HIV and AIDS, renal insufficiency, organ or stem cell transplantation, irradiation, iron overload, skin trauma, broad-spectrum antibiotics, hepatitis, tuberculosis, malignant disease, intravenous drug abuse, by the administration of corticosteroids and immunosuppressive drugs, prophylactic voriconazole for aspergillosis, malnutrition, penetrating trauma/burns, concurrent hemodialysis (especially when using the chelating agent desferrioxamine), use of occlusive dressings/boards, tongue blades, blast injury, malt/lumbar industrial workers, construction workers, and poor wound care.[11],[12]

DM is observed to be a major predisposing factor in 36–88% of all mucormycosis cases. Mucormycosis can occur in both non-diabetic and metabolically controlled diabetic patients as well but when the disease becomes uncontrolled, it leads to the impairment of neutrophil function, phagocytosis, and oxidative reactions along with causing an increase in free iron level which acts as a substrate and thereby enhances the growth of mucormycosis.[13],[14]

More recently, mucormycosis is commonly seen to be associated with corona virus as its predisposing factor. Coronavirus disease 2019 (COVID-19) is an infection that is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). COVID-19 disease has a propensity to cause extensive pulmonary involvement and subsequent alveolo-interstitial pathology that may predispose to invasive fungal infections of the airways including the sinuses and the lungs.[1],[15]

  Clinical Manifestations Top

Clinically, mucormycosis is not associated with any specific age group and both the sexes are equally affected. It occurs in one of the six forms: rhino cerebral, pulmonary, cutaneous, gastrointestinal, disseminated, and miscellaneous. The rhinocerebral form is observed to be the most common form which accounts for 30–50% of all cases of mucormycosis, with Rhizopus being the predominant pathogen involved in its occurrence.[8],[16],[17] This form has been concomitantly associated with poorly controlled DM and diabetic ketoacidosis. The rhinocerebral form is further subdivided into two subtypes: a highly fatal rhino-orbito-cerebral form which is invasive and may involve the ophthalmic and internal carotid arteries and a less fatal rhinomaxillary form which involves the sphenopalatine and greater palatine arteries, thereby resulting in thrombosis of the turbinate and necrosis of the palate.[8],[16],[17]

Site of invasion: Nose, paranasal sinuses, lungs, kidneys, etc.

Mode of spread: Either through direct extension or through blood vessels/lymph vessels.

Sites involved: Palate being the most common site followed by buccal mucosa, maxillary and mandibular lip, and mandible.[8],[16],[17]

Oral considerations: Symptoms involving the oral, cranial, and facial structures account for about 60% of all cases. Intraorally, ulcer with raised erythematous borders with surface of the ulcer appearing black and necrotic with areas of denudation is seen. Other associated signs and symptoms include nasal obstruction, bloody nasal discharge, facial pain and headache, visual disturbances, and facial paralysis.[17]

  Diagnosis Top

It can be done by various methods such as culture, potassium hydroxide smears, and histopathological examination of biopsied specimen by routine hematoxylin and eosin stains as well as by special stains and can confirm the clinical diagnosis with the appearance of right-branching aseptate hyphae, which are considered typical of mucor species, along with evidence of angioinvasion and tissue necrosis. Other laboratory diagnostic modalities include molecular detection of zygomycetes. However, the results so far have been observed to be less than promising. Cerebrospinal fluid analysis has also been reported as helpful in the diagnosis.[8],[18],[19]

  Differential Diagnosis Top

Wegener’s granulomatosis, tuberculosis, squamous cell carcinoma, malignant salivary gland tumor, and tertiary syphilis, because of these pathologies, commonly show involvement of palate in the form of a solitary ulcer like that of mucormycosis.[12]

  Imaging Modalities Top

A clinical suspicion of mucormycosis requires confirmation by radiological examination. Radiographically, opacification of sinuses in conjunction with patchy effacement of bony walls of sinuses may be observed. A computed tomography scan with contrast shows membrane or periosteal thickening and bony disruption. Magnetic resonance imaging scan can demonstrate erosion or destruction of bone and help to delineate the extent of disease.[8],[12],[20]

  Treatment For Mucormycosis Top

It is based on three main principles: reversal of underlying predisposing conditions, prompt initiation of antifungal therapy, and surgical intervention when appropriate.[21]

The role of surgery[22]: Extensive surgical debridement to remove necrotic tissue and establish sinus drainage is essential in the treatment as the involved blood vessels are ischemic and the antifungal drugs would not reach their target tissues. Surgical intervention has been associated with favorable outcome but the guidelines related to the timing and extent of appropriate surgical management have not been clear. Although orbital exenteration has been considered in the context of intracranial spread due to lack of evidence-based studies, surgical intervention is considered. Irrigation of the surgical site with amphotericin B solution has also been proposed based on the vaso-occlusive nature of the infection, leading to reduced delivery of antibiotics to infected areas.

Antifungal therapy: Treatment of the underlying systemic disease, especially control of the glycemic state or modification/cessation of immunosuppressive drugs, helps in decreasing the morbidity and mortality associated with mucormycosis. Amphotericin B deoxycholate when administered intravenously (1–1.5 mg/kg daily) is proven to be the primary therapy for mucormycosis.[12],[20],[23]

Amphotericin B is the polyene antifungal drug which after binding to ergosterol alters the permeability in the fungal cell membrane. Due to its toxicity, the patient has to be monitored for renal damage and anaphylaxis. Liposomal amphotericin B in the initial dose of 5 mg/kg body weight (10 mg/kg body wt. in case of CNS involvement) is the treatment of choice. Each vial contains 50 mg. It should be diluted in 5% or 10% dextrose; it is incompatible with normal saline/Ringer’s lactate. It has to be continued till a favorable response is achieved and disease is stabilized which may take several weeks. Conventional amphotericin B (deoxycholate) in the dose 1–1.5 mg/kg may be used if liposomal form is not available and renal functions and serum electrolytes are within normal limits. Liposomal amphotericin B is less nephrotoxic than conventional amphotericin B.[12],[20],[23]

Iron chelation therapy: Deferasirox and Deferiprone are new iron chelators, which in contrast to Deferoxamine cannot be utilized by the fungi as siderophores. Deferasirox has also been used successfully as salvage therapy in a case of rhinocerebral mucormycosis opening up new areas of clinical research.[12],[20],[24]

Adjunctive therapies: Hyperbaric oxygen therapy has been used as an adjunct to aggressive surgical debridement. Granulocyte colony-stimulating factor may also be administered to improve host defenses and also to enhance leukocyte count to promote immunity.[12],[20],[25],[26],[27]

Prognosis: Prognosis rate has been reported to be 90% or more with mucormycosis, before the administration of amphotericin B and radical surgery. The overall survival rate of diabetic patients with mucormycosis who undergo treatment is approximately 60%.[27]

  Management of Mucormycosis in Covid-19-Affected Top

Since COVID-19 leads to immunosuppression, all physicians should therefore be mindful of the probability of mucormycosis in patients with COVID-19 illness, especially those with comorbidities and patients on immunosuppressive agents or on extensive steroids and broad-spectrum antibiotics which will be leading to the development or exacerbation of a pre-existing fungal disease in the coming future. Control of hyperglycemia, early treatment with liposomal amphotericin B, and surgery are therefore essential for the successful management of mucormycosis. Furthermore, the use of glucocorticoids in mild COVID-19 cases (without hypoxemia) or the utilization of higher dosages should be avoided. Drugs targeting immune pathways such as tocilizumab should be discouraged in the absence of a clear benefit. A delay of even 6 days in initiating treatment doubles the 30-day mortality from 35% to 66%.[1],[15],[16],[17],[28]

  Conclusion Top

Mucormycosis warrants emergency treatment. Despite improvements in imaging modalities leading to earlier diagnoses and increasing therapeutic options, it is still difficult to treat. Recently, it has been considered a concomitant factor in Covid-19 patients because of immunosuppression. Control of hyperglycemia, early treatment with liposomal amphotericin B, and surgery are essential for the successful management of mucormycosis.

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Conflicts of interest

There are no conflicts of interest.

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