COVID-19 associated Orbital Mucormycosis

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 by Michael T Yen, MD on June 16, 2021.

Rhino-orbital cerebral mucormycosis (ROCM) has recently emerged as a serious long-term manifestation in patients affected by Covid-19. The diagnosis of COVID-19 associated mucormycosis remains challenging and requires a high degree of clinical suspicion.

Disease Entity



Alarming rise of rhino-orbital mucormycosis in patients affected with COVID-19

Rhino-orbital cerebral mucormycosis (ROCM) is an uncommon life-threatening invasive fungal infection caused by the angiotropic fungus belonging to the order Mucorales. It is a fulminant disease with high rates of morbidity and mortality despite treatment, that mainly affects immunocompromised patients, as it almost always occurs in patients with uncontrolled diabetes mellitus (70% of the cases present as a complication of a diabetic ketoacidosis (DKA) event), hematologic cancers, and solid organ or hematopoietic stem cell transplants. The condition originates in the nasal region and paranasal sinuses, but is often suspected following orbital spread, explaining its poor prognosis. Depending on the location of the infection, the mucormycosis can be rhino-orbito-cerebral (most common), pulmonary, gastrointestinal, cutaneous, or disseminated, as the infiltrating fungus destroys the surrounding bone and soft tissue through vascular thrombosis and subsequent tissue infarction and may reach the brain with fatal complications. Although it has a low incidence rate, varying from 0.005 to 1.7 per million population, an alarming rise in cases of rhino-orbital mucormycosis in patients with past or current COVID-19 infection has been observed during the recent outbreak. The suspicion or diagnosis of rhino-orbital cerebral mucormycosis triggers a medical as well as surgical emergency with the delay in treatment, increasing morbidity and mortality

Although the majority of reports on COVID-19-associated ocular manifestations describe self-limiting conjunctivitis and rare neuro-ophthalmic manifestations, including optic neuritis and ocular motor cranial neuropathies, the overreaching health implications and long-term sequalae associated with the viral pandemic are still unknown. Separate case reports (10–14) have been emerging describing ROCM coinfection in COVID-19-positive patients. A number of hospitals mostly located in India, Pakistan and Egypt, have reported an increased rate of ROCM cases during the first wave of the pandemic. We set out to identify if this were a true increase and, should it be, review the COVID-19 status of the patients, other associated comorbidities, and clinical manifestations.[1]

We retrospectively reviewed cases presenting with ROCM to the tertiary care of Ain Shams University Hospitals over the 6 monts from March 25, 2020 (when the government imposed partial lockdown due to spike in COVID-19) to September 25, 2020. Case identification was based on the global guideline for the

The work was approved by the ethical committee of the faculty of medicine, Ain Shams University, with written informed consents obtained from patients (or next of kin in case of patient's death).


Mucorales is the largest and best studied order of zygomycete fungi.

  • Rhizopus oryzae
  • Rhizopus microsporus
  • Mucor racemosus
  • Rhizomucor pusillus

Risk Factors

  • critically ill patients who have undergone invasive procedures
  • patients on mechanical ventilation / prolonged ICU stay
  • uncontrolled diabetes
  • long-term corticosteroid therapy
  • long-standing oxygen therapy
  • associated immunodeficiency conditions
  • immunomodulation treatments
  • comorbidities( i.e. malignancy / post-transplant)
  • voriconazole treatment
  • iron and/or aluminum overload
  • protein energy malnutrion

General Pathology

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COVID-19 causes :

  • Dysregulated immunological response
  • Cytokine storm
  • Thrombotic inflammatory phenomenon
  • Microvascular coagulopathies

All of which lead to exhaustion of the immune system, rendering a patient more susceptible to developing opportunistic fungal infections

Primary prevention

Preventative measures against rhino-orbito-cerebral mucormycosis in the setting of COVID-19 include

  • Judicious and supervised use of systemic oorticosteroids in compliance with the current preferred practice guidelines
  • Judicious a. supervised use of locilizumab in compliance with the current preferred practice guidelines
  • Aggressive monitoring and control of diabetes melitus
  • Strict aseptic precautions during oxygen administration (sterile water for the humidifier, daily change of the sterilized humidifier and the tubes)
  • High personal and environmental hygiene
  • Betadine mouth gargle (not nasal drops)
  • Barrier mask covering nose and mouth
  • Consider oral prophylactic oral Posaconazole in high-risk patients (>3 weeks of mechanical ventilation, >3 weeks of supplemental oxygen, >3 weeks of systematic corticosteroids, uncontrolled diabetes mellitus with or without ketoacidosis. prior history of chronic sinusitis, and co-morbidities with immunosuppression)


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Physical examination

Signs & Symptoms

The most common warning signs and symptoms of rhino-orbito-cerebral mucormycosis include :

  • eyelid, periocular/and facial edema swelling
  • rapidly progressive eyelid drooping
  • ocular motility restriction
  • diplopia
  • sudden ptosis
  • sudden vision loss
  • regional facial, orbit, paranasal sinus or dental pain
  • facial palsy / paresthesia / anesthesia
  • nasal stuffiness
  • nasal mucosal erythema, inflammation, purple or blue discoloration, white ulcer, ischemia, or eschar
  • epistaxis
  • mucoid, purulent, blood-tinged or black nasal discharge
  • foul odor
  • palatal eschar
  • eyelid, periocular, facial skin discoloration
  • fever, altered sensorium, paralysis, focal seizures

Clinical diagnosis

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Diagnostic procedures

  • Magnetic Resonance Imaging of the orbit and brain (with gadolinium contrast)
  • Diagnostic nasal endoscopic evaluation: Revealed inflamed and edematous nasal mucosa. Necrotic middle turbinate with eschar. Biopsy from the nasal specimen confirmed the presence of aseptate fungi on the KOH mount. Mucor was seen growing on Sabourds dextrose agar medium on day 3.

Laboratory test

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Differential diagnosis

  • Allergic fungal sinusitis manifesting due to allergic reaction to dematiaceous fungi can produce a clinical picture of sinusitis with proptosis and rhino cerebral mass in immunocompetent hosts. But it never invades the tissue and often lingers for months to years. Many patients could have underlying asthma, allergy, mucosal polyps, and elevated IgE levels. The eosinophil-rich fungal mucin can erode into adjacent orbit and intracranial space. Bony erosions have been reported due to the pressure effect of thick mucin.
  • Invasive aspergillosis in the form of rhino-orbital cerebral aspergillosis can produce a sinusitis-like picture with orbit and brain involvement and is increasingly reported in immunocompromised patients, and the outcome is extremely poor. IV amphotericin, along with surgical debridement, is the key management strategy.
  • Painful eyes could be due to inflamed lids, conjunctivitis, or preseptal and orbital cellulitis.
  • Subperiosteal hematomas, inflammatory pseudotumors, cavernous sinus thrombosis, and orbital neoplasms can produce protrusion of the eyeball
  • Bacterial orbital cellulitis
  • Cavernous sinus thrombosis
  • Orbital apex syndrome


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General treatment

Early recognition and identification are the most important factors for proper management, so that timely intervention can be achieved

Management of predisposing factor

  • Control of diabetes and/or diabetic ketoacidosis
  • Steroid reduction aiming to discontinue rapidly
  • Discontinuation of immunomodulating treatment
  • No antifungal prophylaxis treatment needed

Medical therapy

  • Installation of peripherally inserted central catheter (PICC line)
  • Maintain adequate levels of system hydration
  • IV normal saline infusion before Amphotericin B infusion
  • Antifungal therapy for at least 4-6 weeks
  • Iron chelation therapy
  • Clinical monitoring of patient with radio-imaging for response and to detect disease progression

Medical follow up

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Durgical debridement may be required for extensive resection of all infected and necrotic tissues as an attempt to control the source and reduce fungal load. Debridement also provides adequate tissue biopsy specimens for definite histopathologic confirmation. Dissection is usually continued until normal, well-perfused bleeding tissue is reached since mucormycotic tissues are less likely to bleed due to extensive thrombosis of vessels. Removal of the palate, nose cartilage, and orbit would cause significant disfigurement. The orbital involvement may need orbital decompression or exenteration. The role of routine orbital exenteration or the timing of exenteration is currently unclear, and cases with orbital involvement have also been successfully managed without exenteration.

Surgical follow up

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Additional Resources

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  1. Fouad Yousef A., Abdelaziz Tougan Taha, Askoura Anas, Saleh Mohamed Ibrahim, Mahmoud Mohammad S., Ashour Doaa Maamoun, Ashour Manar Maamoun. Spike in Rhino-Orbital-Cerebral Mucormycosis Cases Presenting to a Tertiary Care Center During the COVID-19 Pandemic. Frontiers in Medicine , Vol.8, 2021,pg 716. DOI:10.3389/fmed.2021.645270. ISSN 2296-858X   
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