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 Table of Contents  
REVIEW ARTICLE
Year : 2022  |  Volume : 14  |  Issue : 2  |  Page : 161-164

Mucormycosis: An emerging concern of orofacial complication in COVID-19 infection


Department of Pediatric and Preventive Dentistry, ITS Dental College, Hospital and Research Centre, Greater Noida, Uttar Pradesh, India

Date of Submission03-Nov-2021
Date of Decision29-Apr-2022
Date of Acceptance11-May-2022
Date of Web Publication01-Jul-2022

Correspondence Address:
Anam Mushtaq
Department of Pediatric and Preventive Dentistry, ITS Dental College, Hospital and Research Centre, Greater Noida, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jorr.jorr_72_21

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  Abstract 


Coronavirus disease (COVID-19) infection has been seen to be associated with secondary bacterial and fungal infections. Mucormycosis has been increasingly reported in patients with COVID-19 infection, especially those with underlying medical conditions such as diabetes mellitus and on steroid therapy. It is an acute invasive fungal infection primarily affecting individuals with suppressed immune system. This article presents the characteristics of mucormycosis infection and its etiological association with COVID-19. Its diagnosis and management based on the current guidelines have also been discussed in this literature review.

Keywords: COVID-19, immunosuppression, mucormycosis


How to cite this article:
Mushtaq A, Shafi RI. Mucormycosis: An emerging concern of orofacial complication in COVID-19 infection. J Oral Res Rev 2022;14:161-4

How to cite this URL:
Mushtaq A, Shafi RI. Mucormycosis: An emerging concern of orofacial complication in COVID-19 infection. J Oral Res Rev [serial online] 2022 [cited 2022 Dec 3];14:161-4. Available from: https://www.jorr.org/text.asp?2022/14/2/161/349716




  Introduction Top


Coronavirus disease (COVID-19) disease pattern can range from mild-to-severe life-threatening conditions of pneumonia which may be associated with superadded coinfections of bacterial and fungal origin.[1] Immunocompromised patients that undergo corticosteroid therapy, artificial ventilation, and those in intensive care units with prolonged hospitalization are prone to nosocomial infections. Underlying medical conditions such as diabetes mellitus further predispose the patients to the risk of coinfections. The development of opportunistic infections such as candidiasis, aspergillosis, mucormycosis, pneumocystis jirovecii, pneumonia, and superinfection by Acinetobacter baumannii and Staphylococcus aureus has been seen associated with COVID-19 patients as well.[2],[3] Recently, a large number of cases with mucormycosis have been reported in patients with active COVID-19 infection as well as those postinfection.[1],[4],]5]


  What is Mucormycosis? Top


Mucormycosis is an angioinvasive fungal disease with characteristic hyphal invasion of tissues leading to infarction and necrosis.[6] It is caused by fungi of the Mucorales order underclass zygomycetes.[7] Mucormycosis has a variable clinical presentation based on anatomic involvement that may be pulmonary, gastrointestinal, cutaneous, sinus-related (pansinusitis, Rhino-orbital, and rhinocerebral), or may even be disseminated.[8] The predominant forms of mucormycosis include rhino-orbito-cerebral and pulmonary mucormycosis and the most common etiological fungi causing mucormycosis include Rhizopus spp., Rhizomucor, Mucor spp., and Lichtheimia spp.[9],[10]

Mucormycosis infection progresses rapidly over a short span of time as the Mucorales release large quantity of airborne spores due to rapid growth and division. It affects mainly the immunocompromised patients with severe comorbidities such as uncontrolled diabetes mellitus, malignancies, patients receiving organ transplantation and hematopoietic stem cell transplantation, cases of severe trauma or burn, corticosteroid therapy, and severe neutropenia.[11] The infection is associated with high-mortality rates ranging from 20% to 50% in localized forms and 70% to 90% in disseminated type of mucormycosis.[12]

In the Asian continent, diabetes mellitus is the most common risk factor, whereas in the United States and European region, malignancies and transplantation pose the highest risk for mucormycosis.[13],[14],[15]


  Immune Suppression in COVID-19 Top


Host immunity and cytokine storm

SARS-CoV-2 infection itself causes impairment in the cell-mediated immune response leading to reduced CD4+ T and CD8+ T cell numbers. Clinical deterioration often occurs rapidly in severe cases which are caused by a systemic hyperinflammation referred as “cytokine storm”. There is an overwhelming increase in the plasma concentrations of pro-inflammatory cytokines such as interleukin (IL)-6, IL-10, granulocyte-colony stimulating factor (G-CSF), monocyte chemoattractant protein 1, macrophage inflammatory protein 1α, and tumor necrosis factor-α.[16] Immunosuppression is deemed the most critical pathophysiologic phenomenon related to COVID-19 infection. According to Zhou et al., 50% of COVID-19 deaths are in patients developing hospital-acquired secondary infections.[17] However, according to an immunoassay study by Remy et al. conducted on COVID-19 patients, it is the host immunity dysfunctioning more than the hypercytokinemia-induced organ injury that occurs as an immunologic defect in COVID-19 eventually reducing the effector immune cells and causing functional T-cell and monocyte function defects.[18] All these immune dysregulating events eventually lead to an immuncompromised state of patients making them prone to secondary infections. Another term associated with this severe immunologic imbalance is “viral sepsis” in severe COVID-19 where patients are unable to obtain viral clearance due to coexisting immunosuppression and hyperinflammation.[19]

Corticosteroid therapy

Various guidelines for the management of COVID-19 patients suggest the use of corticosteroids to provide anti-inflammatory therapy. Although it is beneficial in reducing disease severity, corticosteroids act as a double-edged sword. It has been seen that steroids such as prednisone, dexamethasone, and methylprednisolone reduce the need for mechanical ventilation in admitted patients.[20] Prolonged steroid administration can lead to adverse effects such as fluid retention, hypertension, psychological problems, increased body weight, increased risk of opportunistic infections, osteoporosis, and ocular problems such as glaucoma and cataract.[21] Delayed viral clearance and an increase in secondary infections related to corticosteroid use have also been observed. A multicentric observational study highlights the significant risk in the incidence of angioinvasive maxillofacial fungal infections in patients with diabetes mellitus being treated for COVID-19 infection associated with the administration of corticosteroid.[22]

Medical comorbidities

Worsening of glycemic control in diabetic patients can occur due to COVID-19 infection itself as well as treatment such as steroid therapy can cause an exacerbation of hyperglycemia and eventually lead to fungal infections such as mucormycosis.[22] Uncontrolled diabetes along with prolonged high-dose corticosteroid therapy can alter and reduce the functioning of phagocytes which forms the main host defense mechanism to ward off mucormycosis entry and infection in tissues.[23] In severe cases of viral pneumonia-associated acute respiratory distress syndrome, blood acidosis along with increased serum ferritin levels also increase the risk for mucormycosis by enabling increased uptake of iron by Mucorales species leading to a rapidly spreading fungal infection.[11]

Severe cases that require mechanical ventilation, intubation, oxygen therapy, and use of humidifiers during hospitalization also predispose to secondary infections.[24] Literature search and evidence-based review reveal that mucormycosis reports from India and globally have seen a sudden upsurge recently and a definite association with COVID-19 infection is observed.[1],[4],[5],[22],[25],[26],[27],[28]


  Clinical Features of Mucormycosis Top


Rhino-orbital-cerebral mucormycosis is the most prevalent form in patients with uncontrolled diabetes mellitus. General nonophthalmic signs and symptoms include fever, headache, and altered mental status. Orofacial manifestations can be in the form of facial pain and swelling, nasal discharge or epistaxis, nasal and palatal ulcerations, and sinusitis. Necrosis of oral tissues can be observed as a black eschar which indicates local invasion. It can even manifest as severe forms of bony destruction, paresthesia, and facial nerve paralysis. Ophthalmic signs include ophthalmoplegia, corneal edema, decreased vision, proptosis, or even cavernous sinus thrombosis.[11],[29]


  Diagnosis Tests Top


Mucormycosis can be detected using direct microscopy with fluorescent stains such as Periodic acid–Schiff stain (PAS) and Grocott's Methenamine Silver Stain (GMS) in sputum and cutaneous lesions which reveal nonseptate or pauciseptate ribbon-shaped hyphae of Mucorales. Culture in a routine media at temperatures of 30°C and 37°C shows cotton white-or grayish-black colonies of fungal growth to delineate fungus species. Molecular tests for the diagnosis of mucormycosis include polymerase chain reaction (PCR) assays, High Resolution Melt (HRM), and target gene: 18s, 28s, or rDNA analysis.[25]

Lateral flow immunoassay has also been seen to be promising and more convenient for detecting Mucorales cell wall fucomannan from point-of-care testing of bronchoalveolar lavage, serum, urine, and tissue samples.[30] Specific breath profiles of the volatile metabolite sesquiterpene from different Mucorales species can aid in differentiating infections from each other.[30]


  Management Top


Improvisation of survival rates can be achieved by a prompt diagnosis and therapeutic intervention which encompasses a multidisciplinary approach involving medical, surgical, radiological, and a sound laboratory facility. Antifungal therapy and surgical debridement of necrotic lesions along with the management of underlying medical comorbidities and immunosuppression are effective in the treatment of mucormycosis. Amphotericin B (AMB) is considered the first-line treatment of mucormycosis. In severe cases, combination therapy of AMB with isavuconazole or posaconazole may also be given. Surgical debridement of lesions should be performed along with antifungal medication whenever possible.[31] Liposomal AMB is recommended over conventional AMB deoxycholate due to lesser toxicity, especially in patients with tolerance and renal dysfunction.[31],[32] An initial dose of 5 mg/kg body weight or double dosage in patients with Central Nervous system (CNS) involvement is advised till an appropriate and favorable response to the treatment is manifested. This may be followed by prescribing sustained release of 300 mg posaconazole twice a day for the 1st day and later 300 mg every day. Posaconazole is advised as salvage therapy in cases with AMB tolerance. Alternatively, 200 mg isavuconazole thrice a day for 2 days can also be given instead of posaconazole followed by 200 mg daily.[33] The Indian Council of Medical Research (ICMR) has recently issued guidelines on the management of mucormycosis in COVID-19 patients. ICMR advises monitoring of diabetic patients carefully to avoid progression to ketoacidosis, judicious use of corticosteroids, and antimicrobials. The use of sterile water in humidifiers for oxygen therapy is also advised. Definitive medical management involves the installation of peripherally inserted central catheter line and systemic hydration with infusion of normal saline intravenously before AMB administration. Antifungal therapy is advised for at least 4–6 weeks till signs and symptoms subside. A strict clinical and radiographic monitoring of patients is advised to assess treatment response and progression of infection.[34]


  Conclusion Top


COVID-19-associated mucormycosis is a significant secondary infection that is being frequently reported in COVID-19 patients. Diabetes mellitus and corticosteroid therapy-induced immunosuppression have been seen to be closely associated with the development of mucormycosis as an opportunistic infection. It is advised that steroids be used judiciously in hospitalized patients to avoid severe immune suppression. Dental practitioners must also be vigilant in diagnosis and detecting early signs and symptoms of common forms of orofacial mucormycosis to initiate a prompt treatment for better outcomes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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34.




 

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