A comprehensive overview on COVID-associated mucormycosis

In recent times, numerous reports of systemic fungal infections have been a major concern. The angioinvasive fungal infection, mucormycosis has surged in patients with COVID-19 due to various factors, mainly uncontrolled diabetes and inappropriate corticosteroid use. The prevalence of this acute and fatal fungal infection caused by Mucorales-related fungal species has been highest in the Indian population. COVID-associated mucormycosis (CAM) has a propensity for contiguous spread, and exhibits high morbidity as well as mortality. Unless promptly detected and treated, it is associated with a poor prognosis. A high index of suspicion, aggressive surgical debridement and use of systemic antifungal agents continue to be the standard of care for CAM. Moreover, there is an imperative need to address this public health issue by increasing public awareness and education. This article provides a comprehensive overview on the emergence of CAM during the pandemic, the current burden, pathophysiology, diagnostic interventions and management of CAM in Indian clinical practice.

Investigating factors affecting hospitalization of patients with mucormycosis after contracting COVID-19: a systematic review

Regarding the investigation of the factors related to the hospitalization of patients with Mucormycosis after being infected with Covid-19, several preliminary studies have been conducted in the hospital, but these studies were conducted in a small environment and have a smaller sample size. Therefore, the aim of the present systematic review study is to examine the factors affecting the hospitalization of patients with mucormycosis after being infected with covid-19. Methods: The current systematic review study was conducted according to PRISMA guidelines (preferred reporting items for systematic seviews and meta-analyses). For this study, the keywords "2019-nCoV", "COVID-19", "SARS-CoV-2", "Coronaviruses", "Hospitaliz", "Factor" and "Mucormycosis" in MagIran, SID, ISI, embase databases, ProQuest, PubMed, scopus were searched. Results: diabetes mellitus, old age, high body mass index, kidney disease, high blood pressure and smoking significantly increase the need for hospitalization in patients with mucormycosis after contracting covid-19. Conclusion: The results of the present study showed that the risk of hospitalization due to Mucormycosis after the covid-19 disease is significantly related to obesity, old age and underlying diseases..

Is Serum Ferritin an Early Marker for COVID-19-Associated Mucormycosis?

Background Coronavirus disease 2019 (COVID-19) is a hyperinflammatory disease caused by severe acute respiratory syndrome coronavirus 2, which makes critically ill patients susceptible to invasive fungal infections. Invasive fungal infections such as mucormycosis are associated with high morbidity and mortality. This study aimed to determine the serum ferritin levels in COVID-19-associated mucormycosis (CAM) patients and isolate and identify the fungi causing secondary fungal infections in patients with suspected CAM. Methodology This cross-sectional study was conducted from June to September 2021 among CAM patients admitted to Bowring and Lady Curzon Hospital. After obtaining approval from the institutional ethics committee and valid consent, data regarding demographic details, past medical history, and serum ferritin levels, along with other blood investigations, were carefully collected from patients presenting with clinical features of mucormycosis and a history of COVID-19. Samples were examined under a bright field microscope using wet mounts of samples in KOH, cultured on Sabouraud's dextrose agar, and examined under a microscope after staining with lactophenol cotton blue for the isolation and correct identification of fungi. Statistical analysis was done using Microsoft Excel (Microsoft Corp., Seattle, WA, USA) and SPSS version 26.0 (IBM Corp., Armonk, NY, USA). A p-value less than <0.05 was considered statistically significant. Results A total of 95 patients with CAM were included in this study, comprising 70 males and 25 females. The mean age of presentation was 49.83 ± 12.41 years, with 73% males and 26% females. Type 2 diabetes mellitus was noted in 69% of patients, hypertension in 29%, and steroid use in 42%. The mean serum ferritin level was 537.38 ± 468.88 ng/mL. We found a significant association between increased serum ferritin and a history of diabetes. Serum ferritin levels had a statistically significant correlation with samples of patients who were positive for Mucorales under KOH microscopy. The fungal culture showed the growth of Aspergillus, Mucor, Rhizopus, and Candida. The mean value of serum ferritin in patients who showed mucor growth was 842.09 ng/mL. Conclusions We found a significant increase in serum ferritin levels in CAM patients. Ferritin can be used as an early marker for screening mucormycosis in COVID-19 patients. Monitoring patients with elevated serum ferritin levels in severe COVID-19, glycemic control, judicious use of corticosteroids, early diagnosis, and appropriate treatment can aid in better management of the disease.

Risk factors for pulmonary mucormycosis in subjects with diabetes mellitus-A case-control study.

BACKGROUND: Factors associated with pulmonary mucormycosis (PM) among subjects with diabetes mellitus (DM) remain unclear. Following the coronavirus disease (COVID-19)-associated mucormycosis outbreak in India, specific environmental exposures (especially cattle dung exposure) were proposed as possible aetiology. We hypothesized that environmental factors are associated with PM. We compared subjects with DM with (cases) and without PM (controls). METHODS: In this case-control study, for each PM case, we included five unmatched diabetic controls (hospital [n = 2], community [n = 3]) without PM. We collected information on demography, COVID-19 infection, glycated haemoglobin% (HbA1c), the type of house (pucca vs. kutcha) where the participants reside, and other environmental factors. The primary exposure tested was cattle dung exposure (CDE; using cattle dung cakes as fuel or cattle handling). We performed a multivariate logistic regression to explore factors associated with PM and report the association as an adjusted odds ratio (OR) with 95% confidence intervals (CI). RESULTS: We enrolled 39 PM cases and 199 controls (hospital [n = 80], community [n = 119]). CDE (OR 0.68, 95% CI [0.14-3.31]; p = 0.63) was not associated with increased PM in DM. We found male sex (OR 4.07, 95% CI [1.16-14.31]), higher HbA1c (OR 1.51, 95% CI [1.18-16.32]), COVID-19 (OR 28.25, 95% CI [7.02-113.6]) and residence at kutcha house (OR 4.84, 95% CI [1.33-17.52]) associated with PM. CONCLUSION: Cattle dung exposure was not associated with PM in subjects with DM. Instead, male sex, poor glycaemic control, COVID-19 and the type of housing were associated with pulmonary mucormycosis.

Treatment of pulmonary mucormycosis with adjunctive nebulized amphotericin B (MUCONAB trial): Results of an open-label randomized controlled trial.

BACKGROUND: The role of nebulized amphotericin B (NAB) in managing pulmonary mucormycosis (PM) is unknown. METHODS: In this open-label trial, we randomized PM subjects to receive either intravenous liposomal amphotericin B (control arm, 3-5 mg/kg/day) alone or along with nebulized amphotericin B deoxycholate (NAB, 10 mg twice a day, every alternate day). The primary outcomes were: (1) overall response ('success' [complete or partial response] or 'failure' [stable disease, progressive disease, or death]) at 6 weeks; and (2) the proportion of subjects with adverse events (AE). The key secondary outcome was 90-day mortality. We performed a modified intention-to-treat (mITT) analysis where we included only subjects receiving at least a single dose of NAB. RESULTS: Fifteen and 17 subjects were randomized to the control and NAB arms; two died before the first dose of NAB. Finally, we included 30 subjects (15 in each arm; mean age 49.8 years; 80% men) for the mITT analysis. Diabetes mellitus (n = 27; 16/27 were COVID-19-associated PM) was the most common predisposing factor. The overall treatment success was not significantly different between the control and the NAB arms (71.4% vs. 53.3%; p = .45). Twenty-nine subjects experienced any AE, but none discontinued treatment. The 90-day mortality was not significantly different between the control (28.6%) and NAB arm (53.3%; p = .26). CONCLUSION: Adjunctive NAB was safe but did not improve overall response at 6 weeks. A different dosing schedule or nebulized liposomal amphotericin B may still need evaluation. More research is needed to explore other treatment options for PM.

Production and optimization of novel Sphorolipids from Candida parapsilosis grown on potato peel and frying oil wastes and their adverse effect on Mucorales fungal strains.

BRIEF INTRODUCTION: Mucormycosis disease, which has recently expanded with the Covid 19 pandemic in many countries, endangers patients' lives, and treatment with common drugs is fraught with unfavorable side effects. AIM AND OBJECTIVES: This study deals with the economic production of sophorolipids (SLs) from different eight fungal isolates strains utilizing potato peels waste (PPW) and frying oil waste (FOW). Then investigate their effect against mucormycetes fungi. RESULTS: The screening of the isolates for SLs production revealed the highest yield (39 g/100 g substrate) with most efficiency was related to a yeast that have been identified genetically as Candida parapsilosis. Moreover, the characterizations studies of the produced SLs by FTIR, 1H NMR and LC-MS/MS proved the existence of both acidic and lactonic forms, while their surface activity was confirmed by the surface tension (ST) assessment. The SLs production was optimized utilizing Box-Behnken design resulting in the amelioration of yield by 30% (55.3 g/100 g substrate) and ST by 20.8% (38mN/m) with constant level of the critical micelle concentration (CMC) at 125 mg/L. The studies also revealed the high affinity toward soybean oil (E24 = 50%), in addition to maintaining the emulsions stability against broad range of pH (4-10) and temperature (10-100℃). Furthermore, the antifungal activity against Mucor racemosus, Rhizopus microsporus, and Syncephalastrum racemosum proved a high inhibition efficiency of the produced SLs. CONCLUSION: The findings demonstrated the potential application of the SLs produced economically from agricultural waste as an effective and safer alternative for the treatment of infection caused by black fungus.

Epidemiology of Mucormycosis in Greece; Results from a Nationwide Prospective Survey and Published Case Reports.

Mucormycosis has emerged as a group of severe infections mainly in immunocompromised patients. We analysed the epidemiology of mucormycosis in Greece in a multicentre, nationwide prospective survey of patients of all ages, during 2005-2022. A total of 108 cases were recorded. The annual incidence declined after 2009 and appeared stable thereafter, at 0.54 cases/million population. The most common forms were rhinocerebral (51.8%), cutaneous (32.4%), and pulmonary (11.1%). Main underlying conditions were haematologic malignancy/neutropenia (29.9%), haematopoietic stem cell transplantation (4.7%), diabetes mellitus (DM) (15.9%), other immunodeficiencies (23.4%), while 22.4% of cases involved immunocompetent individuals with cutaneous/soft-tissue infections after motor vehicle accident, surgical/iatrogenic trauma, burns, and injuries associated with natural disasters. Additionally, DM or steroid-induced DM was reported as a comorbidity in 21.5% of cases with various main conditions. Rhizopus (mostly R. arrhizus) predominated (67.1%), followed by Lichtheimia (8.5%) and Mucor (6.1%). Antifungal treatment consisted mainly of liposomal amphotericin B (86.3%), median dose 7 mg/kg/day, range 3-10 mg/kg/day, with or without posaconazole. Crude mortality was 62.8% during 2005-2008 but decreased significantly after 2009, at 34.9% (p = 0.02), with four times fewer haematological cases, fewer iatrogenic infections, and fewer cases with advanced rhinocerebral form. The increased DM prevalence should alert clinicians for timely diagnosis of mucormycosis in this patient population.

A hospital based observational study of clinical spectrum and outcome of mucormycosis during the COVID pandemic

Background : Mucormycosis is a life threatening fungal disease caused by the filamentous fungi mucormycetes. Though a known entity for decades, it began to manifest in an unprecedented manner in the COVID scenario specially with the second wave in India. The objectives were to describe the demographic characteristics, clinical presentations, risk factors, therapy and in-hospital mortality of patients with Mucormycosis. Material and Methods : We conducted a retrospective observational study for a period of six months from March 2021 to August 2021. The data was collected for cases of mucormycosis from multiple centres all over West Bengal and analysed. All consecutive individuals with confirmed mucormycosis were enrolled in this study. The data documenting demographic particulars, presentation, predisposing factors and comorbiditieswere recorded in a pre validated case report form Details of investigation recording site and extent of disease, therapeutic intervention and outcome was mentioned . Statistical analysis was done using SPSS 21.0 for MS-Windows. Results : The total number of cases from March to August 2021 was 263 . There were 171 males and 92 females and the mean age of occurrence was 50.8+or-0.4 years .In West Bengal clusters of cases were being reported most commonly from the districts of North 24 Parganas, Kolkata, Jalpaiguri, Darjeeling and Hooghly. Some cases admitted here hailed from outside states like Bihar, Jharkhand, Odisha and Assam. The majority of the cases 74.22% (196)were COVID Associated Mucormycosis (CAM) while only 25.78% were non COVID associated. Diabetes mellitus was associated in 78.7% and history of prolonged steroid therapy in 57.4% of cases. We encountered rhino orbital mucormycosis in 99.24% of cases and cerebral involvement in 47.3%. They were treated with Amphotericin B deoxycholate along with endoscopic debridement. The most common side effects of Amphotericin B Deoxycholate were hypokalemia (93%), hypomagnesemia (32%) and AKI (74%) of the cases . The number of patients discharged was 16.7% and 10 left against medical advice (LAMA) . In hospital deaths were recorded to be 26.7%. Cause of death was commonly -AKI, septic shock and multiorgan failure . Conclusion : Prevention is better than cure of this devastating disease which is difficult todiagnose and treat . Awareness about mucormycosis and careful clinical evaluation of post-COVID patients is mandatory in this era in order to rapidly diagnose and treat mucormycosis.

Perspective of dental health-care professionals during the second wave of COVID-19 pandemic: a national online survey

Objectives: COVID-19 pandemic has shown a substantial impact on the entire world both physiologically and psychologically. By the hit of the second wave, which opened dangerous gates for secondary infections, apprehension was carried among health-care sectors. These secondary infections were due to decreased immunity. On the other hand, risk modifiers, such as diabetes and hypertension played a leading role in the mortality rate. A substantial number of studies have not been conducted so far regarding the impact of this second wave on dental healthcare professionals. The present study aimed to evaluate the dental healthcare professionals' perspective levels during the second wave of the COVID-19 pandemic through a web-based survey. Material and Methods: A total of 853 responses were gathered by sending 15 questions in Google forms. Data collected were gathered and subjected to statistical analysis, expressed in frequency distribution and Pearson's Chi-square test was performed. Results: Data obtained and projected that the study population expressed higher anxiety and stress levels, despite which was many of them showed an inclination to work during these tough times. The knowledge about secondary fungal infections like Mucormycosis, which was caused due to immune suppression, was abundant among the participants. A significant proportion conveyed the ill effect of COVID-19 on clinical practice and academics as well. Conclusion: Dental professionals have shown a positive perspective despite of higher stress levels and being a part of frontline workers, they are much primed to assure, educate, and treat the patients amidst the COVID-19 pandemic.

Study of admitted patients of mucormycosis: experience of a tertiary care centre

A prospective study was done during mid-April to mid-June 2021 to analyze the sudden rise in cases of Mucormycosis. We assessed characteristics, related comorbidities, disease locale, steroid administration and disease outcome in patients. Cases of Mucormycosis associated with RTPCR positive for Coronavirus disease (COVID-19) and Mucormycosis occurring in patients with negative RTPCR for COVID-19 were compared. A total of 103 Mucormycosis patients were analyzed, 84 (81.55%) were RTPCR positive. Uncontrolled Diabetes Mellitus (70.87%) was the most common comorbidity present among RTPCR positive and negative Mucormycosis patients. Rhino-orbital and Rhino-sinusoidal sites were equally involved (44.0%), followed by Rhino-orbital-cerebral (11.9%) region. We ascribe the spike in Mucormycosis episodes to the trio of diabetes, excessive corticosteroid usage in the face of the COVID-19 Pandemic.

A role of black fungus in COVID-19: a review

Mucormycosis is a rare type of fungal infection commonly known as zygomycosis, the infection tends to crop up more commonly in individuals with low and weakened immunity level, if left untreated, the mucormycosis can be life-threatening and fatal. Mucormycosis previously known as zygomycosis is a consequential type of infection caused by several mildews known as micromycetes. The revised taxonomical studies revealed that the micromycetes causing the infections are classified as the species of phylum Glomeromycota, class Glomeromycetes, subphylum Mucoromycotina, order Mucorales. The genera of Rhizopus, Mucor, Lichtheimia, Cunninghamella, Rhizomucor, and Apophysomyces, constitute the causative agents of the majority of cases of mucormycosis. The angioinvasive type of disorder caused by mucormycosis is further classified as Mucorales. The patients with Diabetes ketoacidosis and diabetes mellitus are at high-risk factors, followed by the patients with organ transplant, immunocompromised disease, and malignancy. The route of exposure to Mucormycosis may be through the wounded infection that can be pneumonic, or dermal in origin. In the ectodermal form, the fungal organism can invade the skin through open or puncture wounds, or the laceration on the skin. However, the infection has a high mortality rate, the key to successful treatment is early diagnosis, and administration of antifungal drugs, with extensive therapy, followed by surgical debridement of the infection. The morbidity and mortality rate are still at a high number, due to the negligence of the patient to seek medical treatment. Hence the early diagnosis and treatment with antifungal drugs with surgical debridement is a must. The efficacy of oral and venous formulations in the treatment of mucorales is still under debate. Despite the aggressive therapy, the mortality rate is increasing worldwide. The studies have to be conducted to invent the fastest treatment protocol for the treatment of Mucormycosis.

Rhino-orbital mucormycosis after COVID-19 in the emergency department

Rhino-orbital mucormycosis (ROM) is an acute and fulminant infection. The number of ROM cases developing after coronavirus disease 2019 (COVID-19) is increasing. A 62-year-old male patient was admitted to the emergency department in northern Syria complaining of new-onset vision loss, swelling, and severe swelling of the left eye. It was noted that a 3-day course of prednisolone 250 mg was given to treat COVID-19. We found that he had a history of diabetes mellitus (DM) for 10 years. Physical examination revealed ptosis, proptosis, and ocular movement restriction in all directions in the left eye. All other systemic examinations were normal. A cranial and orbital magnetic resonance imaging scan performed after hospitalization for further evaluation and treatment showed an increase in the density of the sphenoid, ethmoid, and frontal sinus walls in the left orbit. Despite antifungal and surgical treatment, the patient died on day 14. The use of steroids in treatment and the presence of concomitant DM are the main predisposing factors. The prognosis of this disease, which has a high mortality and morbidity, is adversely affected in geographic regions where health care is inadequate.

Risk factors of mucormycosis in post-COVID-19 patients- a retrospective study

Background: Rhino-orbito-cerebral mucormycosis was seen in increasing severity in the recent second wave of COVID-19 in India. The incidence of mucormycosis is increased significantly in patients with diabetes. The most common cause attributed to the rise of mucormycosis in COVID-19 patients are uncontrolled diabetes. Lymphopenia and increased levels of certain cytokines, such as IL-6, have been closely associated with the disease severity. Aims and Objectives: The aims of this study were to analyze risk factors involved in Mucormycosis in 2nd wave of COVID-19. Materials and Methods: The study was done in the Mucormycosis ward, Department of ENT, Patna Medical College and Hospital, Patna, between May 2021 and July 2021. A total of 100 patients of both gender and all age groups were taken into the study. Results: Out of 100 patients included in the study, 57% (n=57) of patients had history of steroid intake, while 43% (n=43) had no history. About 41% (n=41) of patients needed oxygen support during treatment, while 59% (n=59) had no history of oxygen inhalation. About 88% (n=88) of patients had prior history of diabetes or detected during treatment, while 12% (n=12) had no prior history of diabetes or detected during treatment. About 91% (n=91)of patients had uncontrolled hyperglycemia, while 9% (n=9) had controlled blood sugar level. Conclusion: Uncontrolled hyperglycemia and delta strain are mainly associated major risk factors that lead to such high number of mucormycosis cases in India (post 2nd wave of COVID-19). Steroid role is not that much significant in our study and oxygen inhalation is not associated with mucormycosis.

Observational study of imaging findings in COVID -19 related rhino-orbito-cerebral mucormycosis - a tertiary care center study

Background: There has been a tremendous increase in number of cases of rhino-orbitocerebral involvement with mucor in the COVID era, as reported from India. It is well established that management of ROCM involves early clinical and radiological diagnosis, reversal of underlying risk factors, prompt antifungal therapy and surgical debridement when indicated. Materials &Methods: Multiplanar MR imaging and CT scan were performed for brain, orbit and paranasal sinuses. All the cases were assessed for involvement of the paranasal sinuses, nasal cavities, orbits and brain. Results: 25 cases with ROCM were identified over 8 months. The mean age of the cases was 56.1 years. 18 of the 25 cases had a positive RT-PCR test result at the time of diagnosis with ROCM. 20 cases had poorly controlled diabetes mellitus, 2 had a hematological malignancy, 2 had chronic kidney disease and 1 had ischemic heart disease. There was involvement of the paranasal sinuses, nasal cavities, orbits and brain inclusing necrosis in most of the cases. The number of cases identified during the interval is much higher than the numbers presenting in the prior 2 years during equivalent intervals than those reported in the literature in different settings in the pre-pandemic era. Conclusions: Rhino-orbito mucormycosis can have aggressive necrosis of the involved paranasal sinuses and orbits with or without cerebral extension. Hence, the correct diagnosis is imperative as prompt antifungal drugs and surgical debridement can significantly reduce mortality and morbidity.

Immunity to fungi in the lung.

The respiratory tree maintains sterilizing immunity against human fungal pathogens. Humans inhale ubiquitous filamentous molds and geographically restricted dimorphic fungal pathogens that form small airborne conidia. In addition, pathogenic yeasts, exemplified by encapsulated Cryptococcus species, and Pneumocystis pose significant fungal threats to the lung. Classically, fungal pneumonia occurs in immune compromised individuals, specifically in patients with HIV/AIDS, in patients with hematologic malignancies, in organ transplant recipients, and in patients treated with corticosteroids and targeted biologics that impair fungal immune surveillance in the lung. The emergence of fungal co-infections during severe influenza and COVID-19 underscores the impairment of fungus-specific host defense pathways in the lung by respiratory viruses and by medical therapies to treat viral infections. Beyond life-threatening invasive syndromes, fungal antigen exposure can exacerbate allergenic disease in the lung. In this review, we discuss emerging principles of lung-specific antifungal immunity, integrate the contributions and cooperation of lung epithelial, innate immune, and adaptive immune cells to mucosal barrier immunity, and highlight the pathogenesis of fungal-associated allergenic disease. Improved understanding of fungus-specific immunity in the respiratory tree has paved the way to develop improved diagnostic, pre-emptive, therapeutic, and vaccine approaches for fungal diseases of the lung.

Microbial and clinical epidemiology of invasive fungal rhinosinusitis in hospitalized COVID-19 patients, the divergent causative agents.

Since COVID-19 spread worldwide, invasive fungal rhinosinusitis (IFRS) has emerged in immunocompromised patients as a new clinical challenge. In this study, clinical specimens of 89 COVID-19 patients who presented clinical and radiological evidence suggestive of IFRS were examined by direct microscopy, histopathology, and culture, and the isolated colonies were identified through DNA sequence analysis. Fungal elements were microscopically observed in 84.27% of the patients. Males (53.9%) and patients over 40 (95.5%) were more commonly affected than others. Headache (94.4%) and retro-orbital pain (87.6%) were the most common symptoms, followed by ptosis/proptosis/eyelid swelling (52.8%), and 74 patients underwent surgery and debridement. The most common predisposing factors were steroid therapy (n = 83, 93.3%), diabetes mellitus (n = 63, 70.8%), and hypertension (n = 42, 47.2%). The culture was positive for 60.67% of the confirmed cases, and Mucorales were the most prevalent (48.14%) causative fungal agents. Different species of Aspergillus (29.63%) and Fusarium (3.7%) and a mix of two filamentous fungi (16.67%) were other causative agents. For 21 patients, no growth was seen in culture despite a positive result on microscopic examinations. In PCR-sequencing of 53 isolates, divergent fungal taxons, including 8 genera and 17 species, were identified as followed: Rhizopus oryzae (n = 22), Aspergillus flavus (n = 10), A. fumigatus (n = 4), A. niger (n = 3), R. microsporus (n = 2), Mucor circinelloides, Lichtheimia ramosa, Apophysomyces variabilis, A. tubingensis, A. alliaceus, A. nidulans, A. calidoustus, Fusarium fujikuroi/proliferatum, F. oxysporum, F. solani, Lomentospora prolificans, and Candida albicans (each n = 1). In conclusion, a diverse set of species involved in COVID-19-associated IFRS was observed in this study. Our data encourage specialist physicians to consider the possibility of involving various species in IFRS in immunocompromised and COVID-19 patients. In light of utilizing molecular identification approaches, the current knowledge of microbial epidemiology of invasive fungal infections, especially IFRS, may change dramatically.

Invasive fungal rhinosinusitis (IFRS) may infect people with diabetes, cancer, or COVID-19. In this study, various types of fungi were identified from COVID-19-associated-IFRS, encouraging physicians to consider specific treatments.

Surge of mucormycosis during the COVID-19 pandemic.

Patients with respiratory viral infections are more likely to develop co-infections leading to increased fatality. Mucormycosis is an epidemic amidst the COVID-19 pandemic that conveys a 'double threat' to the global health fraternity. Mucormycosis is caused by the Mucorales group of fungi and exhibits acute angioinvasion generally in immunocompromised patients. The most familiar foci of infections are sinuses (39%), lungs (24%), and skin tissues (19%) where the overall dissemination occurs in 23% of cases. The mortality rate in the case of disseminated mucormycosis is found to be 96%. Symptoms are mostly nonspecific and often resemble other common bacterial or fungal infections. Currently, COVID-19-associated mucormycosis (CAM) is being reported from a number of countries such as the USA, Turkey, France, Mexico, Iran, Austria, UK, Brazil, and Italy, while India is the hotspot for this deadly co-infection, accounting for approximately 28,252 cases up to June 8, 2021. It strikes patients within 12-18 days after COVID-19 recovery, and nearly 80% require surgery. Nevertheless, the mortality rate can reach 94% if the diagnosis is delayed or remains untreated. Sometimes COVID-19 is the sole predisposing factor for CAM. Therefore, this study may provide a comprehensive resource for clinicians and researchers dealing with fungal infections, intending to link the potential translational knowledge and prospective therapeutic challenges to counter this opportunistic pathogen.