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 Table of Contents  
EDITORIAL
Year : 2021  |  Volume : 15  |  Issue : 2  |  Page : 99-101

Post-COVID-19 mucormycosis – Are we through the storm as yet?


1 Dte Gen Dental Services, New Delhi, India
2 Department of Oral and Maxillofacial Surgery, Army Dental Centre (Research and Referral), New Delhi, India

Date of Submission10-Aug-2021
Date of Acceptance14-Aug-2021
Date of Web Publication17-Sep-2021

Correspondence Address:
N K Sahoo
Dte General Dental Services, Block Army HQ, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-4724.326226

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How to cite this article:
Sahoo N K, Saxena V. Post-COVID-19 mucormycosis – Are we through the storm as yet?. J Dent Def Sect. 2021;15:99-101

How to cite this URL:
Sahoo N K, Saxena V. Post-COVID-19 mucormycosis – Are we through the storm as yet?. J Dent Def Sect. [serial online] 2021 [cited 2021 Oct 22];15:99-101. Available from: http://www.journaldds.org/text.asp?2021/15/2/99/326226




  Lurking Danger Top


Post-COVID rhino-maxillary-orbital mucormycosis has been a major surprise in an ever-changing COVID preparedness of the global healthcare services. Since its outbreak achieved unprecedented proportions after the infamous Wuhan outbreak in December 2019, COVID-19 virus has been churning out surprises after surprises and in the bargain posing significant and hitherto unparalleled challenges to the global health community. The second COVID-19 surge, especially in India, has seen a massive number of mucormycosis cases and our healthcare system is still grappling with the ways and means to counter it.


  Rare, Then Pandemic Now Top


Mucormycosis (previously called zygomycosis) is a serious but rare fungal infection caused by a group of molds called mucormycetes. These molds live throughout the environment. The first known case of mucormycosis was possibly one described by Friedrich Küchenmeister in 1855. The genera responsible for human infection are Rhizopus, Mucor, and Rhizomucor; Cunninghamella, Lichtheimia, and Apophysomyces.

In India, the prevalence of mucormycosis is approximately 0.14 cases per 1000 population, which is about 80 times the prevalence of mucormycosis in developed countries.

Mucormycosis mainly affects people who have underlying systemic comorbidities and/or on medications that lower the body's immunity, thereby making them vulnerable to opportunistic infections. It most commonly affects the sinuses or the lungs after inhaling fungal spores from the air. It can also occur on the skin after a cut, burn, or any other type of skin injury.

Mucormycosis has emerged as the third most common invasive mycosis in order of occurrence after candidiasis and aspergillosis in patients with hematological and allogeneic stem cell transplantation. Mucormycosis remains a threat in patients with uncontrolled diabetes mellitus in developed or developing countries alike. Based on anatomic localization and involvement, mucormycosis can be classified into the following six subtypes:

  1. Rhino-maxillary-orbito-cerebral
  2. Pulmonary
  3. Cutaneous
  4. Gastrointestinal
  5. Disseminated
  6. Uncommon presentations.


The underlying systemic conditions largely influence its clinical presentation and outcome.


  Post-COVID Mucor Outbreak - Enigma or a Catastrophe Waiting To Happen Top


We all are aware that COVID-19 is an infective inflammatory disease with multisystem involvement caused by 2019 SARS-CoV-2 virus. The infection manifests itself in a plethora of features major ones being

  1. Markedly raised proinflammatory CD4 T cells and CD8 toxic granules
  2. Cytokine surge
  3. Hemoglobinopathy
  4. Hypercoagulable state
  5. Altered iron metabolism and increased iron overload resulting in hypoxia and multisystem failure in severe cases.


Recently, with the second wave of COVID-19, the Indian subcontinent has witnessed a dramatic rise in mucormycosis infection in patients recovered from COVID-19. This association has been documented in various case reports/case series and institutional experiences. Furthermore, mortality associated with this fungal infection is emerging as a cause of concern in the Indian subcontinent.

Apart from the acknowledged role of ketoacidosis, high blood sugar, and iron metabolism in the pathogenesis of mucormycosis, other factors involved in the pathophysiology of COVID-19 which might alter or enhance the mucormycosis infection are:

  1. Serum ferritin
  2. Free radical-induced endothelitis
  3. Hepcidin activation by viral mimicry
  4. Upregulation of glucose receptor protein (GRP78).


The route of entry of infection is via inhalation. Infection begins initially in the paranasal sinuses with subsequent invasion into the vascular tissue, eventually leading to thrombosis and necrosis of adjacent structures. Patients frequently present with nasal discharge and black palatal eschar. Tissue necrosis, a hallmark of mucormycosis, is often a late presentation.


  Management Strategy - Combating the Black Enemy Top


Clinical examination with a high degree of suspicion shall enable the treating surgeon to quickly diagnose Mucor infection, as time is a major essence and timely intervention significantly reduces the morbidity and mortality associated with the disease. An in-depth preliminary case history recording is an indispensable tool in the diagnosis and treatment of the disease.

Any patient with a complaint of sudden toothache, eye pain, and loosening of the tooth should be inquired about any history of fever, sour throat, loss of sense of smell, hospital admission, oxygen inhalation therapy, and specifically steroid use - its dose and duration need to be taken into consideration as the second surge of COVID-19 infection saw an unwarranted use of steroids, despite the inflammatory markers such as C-reactive protein and D dimer, not suggestive of an impending cytokine storm.

Potassium hydroxide (KOH) mount and tissue biopsy form the cornerstone of the diagnostic algorithm. Appropriate imaging is strongly recommended to document the extent of disease and is followed by strongly recommended surgical intervention. Contrast computed tomography and gadolinium-enhanced magnetic resonance imaging are the mainstay imaging techniques which immensely help in assessing the extent of disease and formulating of a surgical plan.

Any patient with the above-mentioned clinical history and imaging findings should be administered amphotericin B as soon as the KOH mount confirms the presence of fungal elements in the specimen. As tissue biopsy takes time to be processed, this aggressive and proactive approach significantly improves the final treatment outcome.


  Surgical Approach - Collaborative or Competitive? Top


In view of the involvement of multiple anatomical regions of the head-and-neck region, there is ambiguity on the specialty treating the disease. One must remember that a single specialty or a domain-specific surgeon at most of the time shall not be able to manage this quickly fulminating disease. A team comprising physician, otorhinolaryngologist, neurosurgeon, oral and maxillofacial surgeon, and ophthalmologist is an inescapable requirement in treating this multifaceted disease. Frequently, it is the dental surgeon who comes in the first contact with a potential Mucor patient presenting with oral symptoms such as toothache and pain upper/lower jaw. The prosthodontist's role in rehabilitating the Mucor patients should also be borne in mind with an aim to improve the quality of life in the individuals who undergo aggressive debridement and need comprehensive restoring of the masticatory apparatus.

Removal of devitalized tissue, debulking of infected tissue, and theoretically allowing for faster action of antifungals against a smaller burden of fungi remain the mainstay of treatment. Aggressive surgical debridement and amphotericin-B liposomal 3–5 mg/kg yield favorable treatment, resulting in terms of mortality reduction and dissemination at long-term follow-up. However, the cerebral extension of the fungus mandates a higher dose of 10–15 mg/kg and repeated renal function tests to check kidney compliance in patients on long-term amphotericin B therapy. Central retinal artery occlusion is now a well-known ophthalmic complication of COVID-19 that can lead to permanent vision loss. Mucormycosis can cause both central ciliary and retinal artery occlusion. In cases where blindness presents very late and there is clear radiological evidence of invasion of the orbital cavity by the Mucor fungus, exenteration of the involved eye will help reduce gross disease burden and prevent intracranial spread.

First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed-release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in a limited-resource setting.


  Conclusion Top


Mucormycosis if undiagnosed in the initial stages may lead to crippling and debilitating psychosocial impact and deformities in the form of blindness, cerebral involvement, or even death. The enhanced prevalence of mucormycosis in COVID-19 patients is alarming and an area of research. The role of the maxillofacial surgeon as part of the Mucor management team cannot be overemphasized as the domain knowledge and familiarity with the anatomy of the involved facial region make him an integral member of any team involved in surgical planning and its implementation. Use of immunosuppressants should be judicious along with a close follow-up, as surgical procedures aimed at treating rhino-maxillary-orbital mucormycosis such as maxillectomy/orbital exenteration may lead to poor quality of life.






 

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Lurking Danger
Rare, Then Pande...
Post-COVID Mu...
Management Strat...
Surgical Approac...
Conclusion

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