POST EFFECTS OF BLACK FUNGUS MUCORMYCOSIS: A REVIEW

Mucormycosis is a disease caused by the fungi belonging to the order mucorales which affects mainly the immunocompromised patients. These fungi are mainly found in soil and in the decomposition of plants and animals from which the sporangiospores are released in the air which are then inhaled resulting in infection based on the host resistance. The cases are increasing in conditions with malnutrition, diabetes, steroid therapy and acidosis. After aspergillosis and mucormycosis is the third most common invasive fungal infection.The common that been identified include rhizopus, Rhizomucor, Cunninghamella and sakhsanaea. Five major forms of include rhino-orbito-cerebral, pulmonary, cutaneous and is a difference in they in mellitus and hematological malignancies undergoing chemotherapy. While in developing countries they are seen in patients withdiabetes and trauma.

Mucormycosis is a disease caused by the fungi belonging to the order mucorales which affects mainly the immunocompromised patients. These fungi are mainly found in soil and in the decomposition of plants and animals from which the sporangiospores are released in the air which are then inhaled resulting in infection based on the host resistance. The cases are increasing in conditions with malnutrition, diabetes, steroid therapy and acidosis. After aspergillosis and candidiasis, mucormycosis is the third most common invasive fungal infection.The common genera that has been identified include mucor, rhizopus, Rhizomucor, Absidia, Apophysomyces, Cunninghamella and sakhsanaea. Five major forms of infection include rhino-orbitocerebral, pulmonary, disseminated, cutaneous and gastrointestinal.There is a difference in epidemiology of mucormycosis between developed and developing countries. In developed countries even though the disease is uncommon, they are found in patients with diabetes mellitus and hematological malignancies undergoing chemotherapy. While in developing countries they are seen in patients withdiabetes and trauma.

…………………………………………………………………………………………………….... Introduction:-
Covid19 pandemic affected manylivesaroundtheworld. InIndia covid recovered patients were affected by a fungus called black fungi mucormycosis.The severity of the disease dependsupontheimmunity of anindividual. Therearemany fungiinthisworld which can act as an opportunistic pathogen.There are many fungisuchas Aspergillus, Candida, Mucoretc., which can cause infection in human. But the infection caused by Mucormycosisin post covidrecovered patient was found to be a life threatening one. In the review articles we would like to elaborate the habitat, pathogenesis, diagnosis and treatments that are available to treat black fungus and also the effect of black fungusin covidpatients.

Fungus
Fungus is used to cover many organisms together. This group consists of microscopic as well as macroscopic organisms. Microscopic organism which cannot be seen through our naked eyes and can be observed only under the microscope. On the other hand, the macroscopic organisms can be seen through our naked eyes. Fungus can be a unicellular or multicellular organisms.Their mode of nutrition is heterotrophic. Based upon the mode of nutrition fungus can be classified into saprophytes, parasites, symbionts and Predacious Fungi.  2000). Sterflinger&Krumbein (1995) assumedthat the ability to grow meristematicallyprovides the colonies an optimal surface/volume ratio for enhanced stress tolerance. In particular, they resist raised temperatures, poorwater availability (

Pathogenesis
Mucorales infects the head and neck region is Rhino-orbital-cerebral type. This is the most usual type of infection (Parfrey1986.) Initially infection was found in the palate or the paranasal sinuses (one of many small hollow spaces in the bones around the nose), progresses to the orbit and, if not diagnosed early, it will enter into the brain (Yohai RA, Bullock JD, Aziz AA, Markert RJ 1994).

Pulmonary Mucormycosis
The second most common site of involvement of Mucoralesinfection is lungs which is Pulmonary type (Parfrey NA. 1986). Majority of cases is spotted in leukaemia patients. Primary route of infection is inhalation of spores (Bigby TD, Serota ML, Tierney LM Jr, Matthay MA., 1986). Individuals with leukaemia, lymphoma and severe neutropenia are more susceptible and develop pulmonary mucormycosis (Meyer RD, Rosen P, Armstrong D., 1972). Patients with solid tumours (sarcomas, carcinomas and lymphomas) rarely develop pulmonary mucormycosis (Solano T, Atkins B, Tambosis E, Mann S, Gottlieb T., 2000).

Cutaneous Mucormycosis
Break in the skin's integrity from surgery, burns, soiled trauma, motor vehicle accidents, bone-fractures, intravenous lines, insect bites, cactus spine injuries, abrasions, lacerations, biopsy sites, allergen patch testing, contaminated adhesive tapes and intramuscular injections can promote Cutaneous mucormycosis (Chakrabarti A, Kumar P, Padhye AA et al.,1997) Stiffness and blood discharge from nose, palatal ulceration, numbness in the middle third of the face and necrotic alveolus. Individuals who lack phagocytes or who have impaired phagocytic function are at higher risk of mucormycosis. Individuals with neutropenia (when a person has low level of neutrophils) are at increased risk for developing mucormycosis (Sugar AM, 2005). So, neutrophils can fight infections by destroying harmful fungi that invade the body. Normal hosts kill Mucorales by the generation of oxidative metabolites and defensins (cysteinerich cationic proteins) with the help of both mononuclear and polymorphonuclearphagocyte. In the sightof hyperglycemia and low pH, which is found in patients with diabetic ketoacidosis (DKA), phagocytes are unable to function normally and have weakend or damaged chemotaxis and flawed intracellular lethalby both oxidative and non-oxidative mechanisms (Waldorf AR, Ruderman N, Diamond RD. 1984).
Inhalation of Mucoralessporangiosporesby immunocompetent patient does not result in the development of mucormycosis because their body is able to recognize antigens and act against them. In comparison, corticosteroidimmunosuppressed (steroids work by decreasing the inflammation and reducing the activity of the immune system) or individuals with DKA die of progressive pulmonary and hematogenously disseminated infection (Lamaris GA, Ben-Ami R, Lewis RE, Chamilos G, Samonis G, Kontoyiannis DP, 2009). Overuse, misuse of steroids is the major cause behind mucormycosis (Dr.RandeepGuleria, director of the AIIMS).

Diagnosis
Early diagnosis of mucormycosis is importantas it can increase the rate of survival and can reduce surgical resection, suffering and disfigurement. Mucor can be cultured on both bacterial and fungal cultures at a temperature of 25-55°C (Forbes BA, Sahm DF, Weissfeld AS, 1998). Mucorales present in clinical specimen can grow at a temperature of 37°C (Sugar AM. 1992) forming fluffy, grey or brownish colonies. In patients with hematological malignancies only 23-50%cases are diagnosed with ante mortem of mucormycosis. Direct microscopy of bronchoalveolar lavage with transbronchial biopsy may increase the yield of diagnosis. Culturing of the specimen has less sensitivity as it shows negative in 50% of the mucormycosis cases. Molecular based assays in the diagnosis of mucormycosis include polymerase chain reaction (PCR) (

Treatment
The diagnosis and treatment for mucormycosis should be started at earlier stage to reducethe mortalityrate. Mucormycosis has developed a high resistance towards most of the antifungal drugs. The most effective against the mucormycosis is amphotericin Bexcept for Cunninghamellaand Apophysomyces (SalasV, Pastor FJ, Calvo E et al., 2012). Theantifungal agents used for mucormycosisis polyene whichis mostpreferred. Even though amphotericinBdeoxycholatehasbeenused manyyears, a lipid formulation ofamphotericin B deoxycholateare lessnephroroxic andcan beadministratedforlongerperiodwith higher dosage when compared to amphotericin B deoxycholate (Walsh et al., 1998).

Effect of Black Fungus on Covid Patients
In post-COVID-19 stage Black Fungus is observed as secondary infection in COVID-19 infected patients. Mucormycosis affect nose, eyes, brain and sinuses recovering COVID-19 patients should look for medical help when they haveswelling in the face, pain and numbness, Unusual (bloody or black-brown) discharge from the nose, Swollen eyes, Nasal or sinus congestion, black lesions on nasal bridge or upper inside of the mouth (ICMR guidelines). Limitthe usage ofsteroidsfor 5 to10 days to mildto moderate dosagetopeoplein early-stage or with mild COVID-19infections can prevent the patients from mucormycosis. Early diagnosis of mucormycosis is essential as fungi has invasive ability into blood vessels, embolizing to distant organs, including the brain.

Conclusion:-
More cases of mucormycosismay be due to increasing numbers of immunocompromisedpatients. Thereare no specific clinical or radiological features makingdiagnosis more difficultand challenging. Diagnostic optionsare limited with variable results. The risk factors are diabetes mellitus, burns, iron overloaded, transplantation, chemotheraphy, intravenous drug use. The imaging studies of mucormycosis are plain X-ray, CT Scan, MRIScans andChest CT/MRI. Mucormycosis carries mortality rate of 50-85%.PosaconazoleandIsuvaconazole can be tried duringtreatment. Duration of treatment is highlyindividualized.