Mucormycosis: Deadly Black Fungus affecting COVID 19 patients- All You Need To Know!

MUCORMYCOSIS 

Black Fungus Affecting Post-COVID 19 Patients

Mucormycosis-Black Fungus Infection

Mucormycosis is a group of life-threatening infections that occurs in patients who are immunocompromised caused by fungi of the order Mucorales of the subphylum Mucoromycotina (class Zygomycetes). 

Post-COVID 19 mucormycosis, maybe being triggered by the use of steroids, used in treatment for severe and critically ill Covid-19 patients.

It is caused by exposure to mucor molds such as Rhizopus oryzae Rhizopus Delmar Rhizopus microsporus Rhizomucor Mucor Actinomucor which is commonly found in soil, plants, manure, and decaying fruits and vegetables. 

Pathogenesis 

Who Are At Risk Of Mucormycosis ?:

Mucormycosis typically occurs in patients with: 

• Diabetes mellitus.
• Hematopoietic stem cell transplantation (HSCT).
• Prolonged neutropenia(low number of white blood cells).
• Malignancy.
• Long-term corticosteroid use. 
• Hemochromatosis(Too much iron in the body).
• Use of steroids, in treatment for severe and critically ill Covid-19 patients, =>immunosuppression by sequestration of CD4+ T-lymphocytes in the reticuloendothelial system and by inhibiting the transcription of cytokines.

Do's and Don'ts to Prevent Mucormycosis in post-Covid 19 patients as per ICMR guidelines

Do's

• Control hyperglycemia
• Use masks if you are visiting dusty construction sites
• Wear shoes, long trousers, long sleeve shirts, and gloves while handling soil (gardening), moss, or manure
• Maintain personal hygiene 
• Monitor blood glucose level post-COVID-19 discharge and also in diabetics
• Use steroid judiciously – correct timing, correct dose, and duration
• Use clean, sterile water for humidifiers during oxygen therapy
• Use antibiotics/antifungals judiciously

Don'ts

• Do not miss warning signs and symptoms
• Do not consider all the cases with a blocked nose as cases of bacterial sinusitis, particularly in the context of immunosuppression and/or COVID-19 patients on immunomodulators
• Do not hesitate to seek aggressive investigations, as appropriate (KOH staining & microscopy, culture, MALDI-TOF), for detecting fungal etiology
• Treat mucormycosis without delay.

Clinical manifestations of Mucormycosis:

Clinical manifestations can be divided into six clinical syndromes:

• Rhino-orbital-cerebral.
• Pulmonary.
• Cutaneous.
• Gastrointestinal.
• Disseminated.
• Miscellaneous.

What Is Rhino-Orbital-Cerebral Mucormycosis?

Occur mainly in patients with diabetes, often along with glucocorticoid-induced diabetes mellitus. 

Initial symptoms:

• Eye or facial pain and facial numbness.
• Blurry vision. 
• Fever may be present (50% Cases).
• White blood cell counts are elevated. 

If untreated, infection usually spreads from the ethmoid sinus to the orbit => failure of extraocular

muscle function and proptosis(Bulging of the eyes) along with chemosis(a sign of eye irritation). 

From the orbit spreads to the frontal lobe of the brain and via venous drainage to the cavernous sinus. 

This condition can lead to cavernous sinus thrombosis(blood clot in the cavernous sinuses).

The rate of progression is extremely variable and is possibly dependent on the immune status of the patient and the causative Mucorales species, some of which are more virulent and have faster growth rates than others. 

Patients may go from initial symptoms to death in days or it can take months or even a year or more for progression to occur.

Pulmonary mucormycosis

Symptoms 

• Dyspnea. 
• Cough.
• Chest pain.
• Fever. 

Angioinvasion => necrosis, cavitation, and hemoptysis(Small amounts of blood mixed with sputum). 

Chest radiography shows Lobar consolidation, isolated masses, nodular disease, cavities, or wedge-shaped infarcts. 

CT is the most preferred method for determining the extent of pulmonary mucormycosis.

Cutaneous mucormycosis: 

Caused due to external implantation of the fungus or from hematogenous dissemination. such as soil exposure from trauma (motor vehicle accident, a natural disaster, or combat-related injuries), penetrating injury with plant material (thorn), injections of medications (insulin), catheter insertion, contamination of surgical dressings, and use of tape to secure endotracheal tubes. 

Cutaneous disease is highly invasive, penetrating into muscle, fascia, and even bone. 

Gastrointestinal mucormycosis: 

Occurs mainly in premature neonates in association with disseminated disease and necrotizing enterocolitis. , adults with neutropenia, glucocorticoid use, and other immunocompromising conditions.

Symptoms:

• Nonspecific abdominal pain. 
• Nausea and vomiting.
• Gastrointestinal bleeding.  

Fungating masses may be observed in the stomach at endoscopy. 

The disease may progress to visceral perforation(hole in the wall of part of the gastrointestinal tract).

Hematogenously Disseminated mucormycosis: 

Can originate from any primary site of infection. 

The most common site of spread is the brain, but metastatic lesions may also be found in any other organ.

Miscellaneous forms may affect anybody's site, including bones, mediastinum, trachea, kidneys, and peritoneum (in association with dialysis).

Diagnosis:

Biopsy with histopathologic examination is the most sensitive and specific modality for definitive diagnosis. 

Biopsy reveals characteristic wide (≥6- to 30-μm), thick-walled, ribbon-like, aseptate hyphal elements that branch at right angles for Rhizopus Delmar in infected brain

Other fungi, such as Aspergillus, Fusarium, and Scedosporium species, have septa, thinner, and branch at acute angles. 

The positive culture test is done for definitive species identification

Treatment:

General principles

Enchaining chances for successful treatment of mucormycosis requires three steps: 

• Early initiation of therapy 
• Rapid reversal of underlying predisposing risk factors, if possible
• surgical debridement, when possible

Therapy often must be started empirically before the diagnosis is established

Rapidly Reverse (or prevent) underlying defects in host defense during treatment (e.g., by stopping or reducing the dosage of immunosuppressive medications or by rapidly restoring euglycemia and normal acid–base status).

Iron administration to patients with active mucormycosis should be avoided, as iron exacerbates infection

Anti-Fungal Therapy

First-Line Antifungal Therapy:

AmB(amphotericin B) deoxycholate

Dose: 1.0–1.5 mg/kg once per day

Advantage: Inexpensive, used over 5 decades

Disadvantage: Highly toxic, Poor CNS penetration

Liposomal amphotericin B(LAmB)

Dose:5–10 mg/kg once per day

Advantage: Less nephrotoxic than AmB deoxycholate, Better CNS penetration than AmB deoxycholate

Disadvantage: Expensive

Amphotericin B lipid complex (ABLC)

Dose:5 mg/kg once per day

Advantage: Less nephrotoxic than AmB deoxycholate

Disadvantage: Expensive, less efficacious than LAmB for CNS infection

Liposomal amphotericin B (LAmB) is preferred over amphotericin B lipid complex (ABLC) for management of the central nervous system (CNS)

Second line Antifungal Therapy: 

Isavuconazole

Dose:200 mg of isavuconazole

(372 mg of isavuconazonium sulfate), load q8h × 6 followed by once-daily dosing

Advantage: Efficacy similar to that of LAmB in mouse models

Disadvantage: less clinical experience

Posaconazole

Dose:200 mg four times per day

Advantage: Retrospective data for salvage therapy in mucormycosis

Disadvantage: Substantially lower blood levels than isavuconazole, No data on initial therapy for mucormycosis, and no evidence for combination therapy with posaconazole