COVID -19 and MUCORMYCOSIS (BLACK FUNGUS)

BY SECOND CONSULT Published on June 1, 2021

Coronavirus 2019 or COVID-19 is an ongoing Pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)

Mucormycosis:

  • Potentially dangerous invasive fungal infection
  • Increasingly reported in patients affected with COVID-19 
  • Seen mostly 1-2weeks after onset of covid 
  • Also described in an individual occurring simultaneous with onset of Covid infection.

Probable causes:

  • Poorly controlled diabetes (upto 70% cases) , 
  • Use of corticosteroids , 
  • Broad spectrum antibiotics and 
  • Other immunosuppressive therapies like IL-6 inhibitors in the setting of COVID-19 management. 

Most common form of acquisition of the infection is through inhalation of the spores.

Presentation:

  • Devastating involvement of the facial structures (Rhino-Orbital-Cerebral) 
  • Lung (Pulmonary) 
  • Also well described in Skin, Gastrointestinal system and other organ systems.

Rhino Orbital Cerebral form: Most common presentation

  • Acute sinusitis-nasal congestion, 
  • Discharge, 
  • Headache, 
  • Sinus pain.

Spreads rapidly causing destruction of contiguous structures.

Pulmonary Disease: Less common 

  • Fever, 
  • Hemoptysis and 
  • Contiguous spread to Heart/Mediastinum.

Usually secondary to Cerebral or Pulmonary disease and uniformly fatal in most scenarios.

Gastrointestinal system: Less common 

  • Stomach is most common site followed by colon. 
  • Abdominal pain.
  • Hematemesis and malena. 
  • Complications include perforation of bowel, peritonitis, bowel ischemia and shock which are often fatal.

Skin involvement: occurs mostly by direct inoculation through trauma.

  • Mostly as a single painful cellulitic lesion that often erodes into deeper dermis. 

Traumatic wounds like bites, injection sites, traumatic wounds, can get complicated with tissue necrosis though deep tissue invasion. Cutaneous form has better prognoses than most forms of mucor as it is usually local in nature. 

Kidney: Renal mucor is mostly acquired through hematogenous spread and relatively rare in occurrence.

It manifests with flank pain, fever and renal failure rapidly ensues depending on unilateral or bilateral involvement.

Isolated CNS disease: occurrence is rare outside the setting of Rhino cerebral form but is well described. 

It is mostly acquired through hematogenous spread especially in IV drug users. Mostly involves basal ganglia with focal deficits and mental obtundation.

Risk Factors Unique to COVID -19 setting:

  • Immune dysregulation/suppression from Covid infection itself.
  • Underlying Diabetes that’s worsening due to Steroid use.
  • Extensive Steroid use for suboptimal indications in COVID-19 can cause or worsen Mucor infection.
  • Concomitant use of broad-spectrum antibiotics and immunosuppressives like IL-6 inhibitors has been suspected as likely culprit as well.
  • Critical illness with prolonged ICU stays/Mechanical ventilation/Risk factors for colonization with fungal organisms seem to predispose to Mucor

Diagnosis 

  • High index of suspicion especially in critically ill patients.
  • Imaging with CT initially, followed by MRI which is useful to detect involvement of orbit, cavernous sinus and intracranial structures.
  • If needed, CT Chest and abdomen.
  • Biopsy of affected tissue is gold standard. 
  • Culture is not full proof, and neither are commonly used fungal blood markers like Beta D Glucan and Galactomannan tests.
  • PCR based sequencing and Mass spectrometry are promising tests with high yield that are just beginning to be used.

Procedure 

  • Endoscopic exam and biopsy of sinuses.
  • Respiratory cultures in clinical setting for diagnosing pulmonary Mucor.
  • BAL /Sputum cultures 
  • Lung Biopsy.
  • EGD for gastric mucor.
  • Isolated CNS cases usually have negative CSF studies on lumbar puncture.

Treatment 

  • Control of: Diabetes, ketoacidosis, Neutropenia, Immunosuppression.
  • IV Amphotericin (Abelcet/liposoma) is drug of choice initially which should be started early to prevent mortality/morbidity.
  • Posaconazole /Isavuconazole used after initial control or if Amphotericin cannot be used.
  • Medications are usually needed for several weeks to months.
  • Concomitant aggressive surgical debridement to remove necrotic tissue (can lead to disfigurement and structural complications).

Prognosis

Poor outcome overall unless treated aggressively and in a timely manner.

  • Rhino cerebral form: upto 25-60% mortality.
  • Delayed diagnosis, brain involvement, cavernous sinus involvement and use of iron chelators is associated with higher risk of death.
  • Pulmonary form: upto 90% risk of mortality as surgical options are limited.
  • Disseminated Mucor: upto 100% fatal.

Recommendations in the setting of Covid -19

  1. Avoidance of steroid use unless indicated for treatment. 
  2. Use of steroids when indicated should be judicious in dose and duration.
  3. Meticulous control of hyperglycemia especially in diabetics and avoidance of ketoacidosis.
  4. Avoidance of other experimental or potent immunosuppressive therapy unless benefits outweigh risks in an individual context.
  5. High index of suspicion to diagnose Mucormycosis in the clinical setting especially critically ill Covid patients admitted to ICU.
  6. Once diagnosed, need a multidisciplinary team for aggressive and timely medical therapy along with appropriate surgical intervention.

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