Cross-sectional study to describe the severity, bio-chemical associations, and final outcomes of COVID-19-associated rhino-orbital-cerebral mucormycosis in a tertiary hospital of East India.

Purpose: The second wave of coronavirus disease 2019 (COVID-19) pandemic triggered a mucormycosis epidemic in India. Diabetes mellitus and dysregulated immune response were contributors, and rhino-orbital-cerebral mucormycosis (ROCM) was the most common presentation. It is however not known whether bio-chemical parameters at presentation correlate with stage of ROCM or final outcome in terms of vision or mortality. Methods: This retrospective, hospital-based study included all in-patients of mucormycosis with ophthalmic manifestations at presentation admitted during June 1, 2021 to August 31, 2021. It aimed to evaluate the association between severity of infection, serum levels of HbA1c, ferritin, interleukin-6 (IL-6), C-reactive protein (CRP), and D-dimer levels at presentation and outcome. Results: There were altogether 47 eligible cases having a mean age of 48.8 ± 10.9 years with a male:female ratio of 2.6:1; forty-two (89.4%) had pre-existing diabetes, and five (10.6%) had steroid-induced hyperglycemia. The mean HbA1c among diabetics was 9.7 ± 2.1. HbA1c and serum CRP showed an increase over subsequent stages, which was not statistically significant (P = 0.31). IL-6 values for all stages were similar (P = 0.97). Only serum ferritin levels showed a statistically significant increase over stages (P = 0.04). IL-6 was significantly lower (P = 0.03) in patients who survived, whereas CRP levels were significantly lower in patients who had final visual acuity (VA) better than only perception of light (P = 0.03). Conclusion: Uncontrolled diabetes mellitus is a significant association of ROCM. Serum ferritin levels at presentation best correlate with extent of the disease. CRP levels are best to prognosticate cases that will have sufficient VA to carry on activities of daily living, whereas IL-6 levels are best associated with survival.

Pneumonia During the COVID-19 Pandemic in Hubei Province, China: a Case Report of Mucormycosis.

BACKGROUND: Mucor infection cannot be ignored in patients with pulmonary shadowing with cavitation. This paper reports a case of mucormycosis during the COVID-19 pandemic in Hubei Province, China. METHODS: An anesthesiology doctor was initially diagnosed as COVID-19 due to changes in lung imaging. After anti-infective, anti-viral, and symptomatic supportive treatment, some of symptoms were relieved. But some symptoms -'chest pain and discomfort', accompanied by chest sulking and short breath after activities, did not ease. At last, Lichtheimia ramose was detected later by metagenomic next generation sequencing (mNGS) in the bronchoalveolar lavage fluid (BALF). RESULTS: After adjusting amphotericin B for anti-infective treatment, the patient's infection lesions were shrunk and the symptoms were significantly relieved. CONCLUSIONS: The diagnosis of invasive fungal infections is very difficult, and mNGS can make an accurate pathogenic diagnosis of invasive fungal diseases for the clinic and provide a basis for clinical treatment.

Utility of itraconazole and terbinafine in mucormycosis: a proof-of-concept analysis.

An epidemic of mucormycosis followed the second wave of COVID 19 in the state of Uttar Pradesh, India in May 2021. This epidemic, however, had additional challenges to offer in the form of acute shortage of all forms of amphotericin B, posaconazole and isavuconazole. It was, therefore, planned to assess the trends in minimum inhibitory concentration (MIC) of antifungal agents, viz itraconazole and terbinafine, and provide a template for personalized therapy to see whether the results could be translated clinically. This is an observational, single-center study. Samples comprising nasal swab, nasal and paranasal sinus tissue, brain tissue, brain abscess and orbital content, derived from 322 patients from northern India with mucormycosis, of whom 215 were male and 107 were female, were used for analysis. Cultures were identified both by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and conventional methods of identification. Antifungal susceptibility was done for amphotericin B, posaconazole, isavuconazole, itraconazole and terbinafine as per Clinical Laboratory Standard Institute M38-A2. The outcome was identification of the species of mucormycosis and susceptibility to itraconazole and terbinafine besides other primary antifungal agents. Patients or the public were not involved in the design, or conduct, or reporting or in the dissemination plans of our research. Of 322 patients, 203 were culture-positive, of whom 173 were positive by both MALDI-TOF and conventional methods of identification. Final antifungal susceptibility testing was available for 150 patients. The most common Mucorales found to cause this epidemic was Rhizopus oryzae, followed by R. microsporus Amphotericin B, posaconazole and isavuconazole had low MIC values in 98.8% of all Mucorales identified. The MIC of itraconazole was species-dependent. 97.7% of Roryzae had MIC ≤2 µg/mL. However, only 36.5% of Rmicrosporus had MIC ≤2 µg/mL. For terbinafine, 85.2% of R. microsporus had MIC ≤2 µg/mL. We conclude that identification at the species level is required as antifungal susceptibilities seem to be species-dependent. Assessment of the efficacy of itraconazole and terbinafine warrants further studies with clinical assessment and therapeutic drug monitoring as they seem to be potential candidates especially when the primary agents are not available.

Mucormycosis: The hidden and forgotten disease.

Mucormycosis is a rare but serious fungal infection caused by a group of moulds called mucormycetes. More attention has recently been paid to it due to its association with coronavirus disease 2019 (COVID-19). Thus, it is important to review the progress of studies on mucormycosis and highlight the important findings in relation to epidemiology, clinical manifestation, major risk factors, diagnostic strategies and management. An electronic literature search was performed in PubMed using the keywords: Rhizopus, Mucorales, mucormycosis, zygomycosis, zygomycetes, COVID-19, the drugs (azoles, posaconazole, isavuconazole, amphotericin B pharmaceutical preparations and caspofungin), combination therapy, diagnosis and clinical manifestations. Studies written in the English language from January 1960 to 2021 were considered for this review article. All search results were reviewed, and the relevance of each article was determined by the authors independently. The review emphasized the fact that the diagnosis of mucormycosis is difficult, it is necessary to have a high index of suspicion to identify it, surgical debridement should be done prior to the dissemination of infection to improve clinical outcomes and identifying underlying risk factors is important for proper treatment. Moreover, antifungal therapeutic options are few with polyenes and their combinations should be appropriate for empirical therapy while posaconazole and isavuconazole are best reserved for de-escalation, refractory cases or patients intolerant to amphotericin B.

Mucormycosis, past and present: a comprehensive review.

Mucormycosis is an emerging opportunistic angioinvasive fungal infection. Predisposing factors such as diabetes, neutropenia, long-term corticosteroid therapy, solid organ transplantation and immunosuppression contribute to its occurrence. This disease was not of significant concern prior to the COVID-19 pandemic, but gained prominence due to infections in COVID-19 patients. Mucormycosis needs special attention and coordinated efforts of the scientific community and medical professionals to reduce morbidity and mortality. Here we present an overview of the epidemiology and prevalence of mucormycosis in the pre- and post-COVID-19 eras, the factors that contributed to the abrupt increase in COVID-19-associated mucormycosis (CAM), the actions taken by the regulatory agencies (including Code Mucor and CAM registry), the existing diagnostic tools and CAM management strategies.

The devastating effects of the COVID-19 pandemic have been further enhanced by various secondary illnesses, particularly opportunistic fungal infections such as mucormycosis. Mucormycosis or 'black fungus' primarily affects people with weakened immunity, those with medical conditions such as diabetes or cancer and those who use medications that reduce the body's capacity to resist infections and disease. The infection starts in the sinuses or the lungs after breathing in spores of the black fungus from the air. In just 2 months between 5 May and 12 July 2021, this uncommon but fatal fungal illness was responsible for 41,512 cases and 3554 fatalities in India alone. The government of India declared a mucormycosis epidemic in May 2021. The majority of such cases occurred during active SARS-CoV-2 outbreaks in India in 2021. Black fungus took over while the host defenses were compromised and the globe was preoccupied tackling the COVID-19 pandemic. Steroids prescribed in amounts and time spans that far exceeded WHO recommendations to manage severe COVID-19 cases, potentially weakened patients' immune systems, and raised blood sugar levels making them vulnerable to fungal invasion. Early diagnosis and treatment are the keys to a patient's survival. Simple means such as maintaining hygienic conditions, avoiding contact with an infected person, judiciously using steroid medications and antibiotics and properly managing high blood sugar can help protect an individual from black-fungus infection.

Mucormycosis infection associated with global COVID-19 pandemic - an institutional histopathological study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) in the recent times have instilled signs of immunosuppression globally which has further precipitated increasing range of opportunistic infections. Mucormycosis is a distressing opportunistic fungal infection with a high incidence and is the third commonest acute invasive infection following candidiasis and aspergillosis. The aim of the present observational study is to delineate the enigmatic histopathological profile between mucormycosis cases seen prior to pandemic (PPM) and pandemic associated mucormycosis (PAM). MATERIAL AND METHODS: Tissue archives of 105 histopathologically diagnosed cases of mucormycosis were included and analysed for demographical details and histopathological parameters like fungal load and localization, granuloma formation, necrosis, inflammatory infiltrate and tissue invasion. RESULTS: 0ut of 105 included cases, 11/105 (10.48%) were reported PPM and 94/105 (89.52%) PAM. Among 94 cases of PAM, 51/94 (54%) cases also showed COVID-19 positivity, while 43/94 (46%) did not. Of all the histological variables, increased fungal load and necrosis were observed in PAM relative to PPM cases. CONCLUSIONS: The histopathological variables like fungal load, necrosis, granuloma formation and tissue invasion, could help the clinician in assessing the clinical status at the time of tissue diagnosis and improve the treatment accordingly.

COVID-19-associated mucormycosis: a systematic review and meta-analysis of 958 cases.

BACKGROUND: Mucormycosis, a rare fungal infection, has shown an increase in the number of reported cases during the COVID-19 pandemic. OBJECTIVES: To provide a comprehensive insight into the characteristics of COVID-19-associated mucormycosis, through a systematic review and meta-analysis. METHODS OF DATA SYNTHESIS: Demographic information and clinical features were documented for each patient. Logistic regression analysis was used to predict the risk of mortality. DATA SOURCES: PubMed, Scopus, Web of Science, Cochrane, CINAHL, Ovid MEDLINE, and FungiSCOPE. STUDY ELIGIBILITY CRITERIA: Studies reporting individual-level information in patients with adult COVID-19-associated mucormycosis (CAM) between 1 January 2020 and 28 December 2022. PARTICIPANTS: Adults who developed mucormycosis during or after COVID-19. INTERVENTIONS: Patients with and without individual clinical variables were compared. ASSESSMENT OF RISK OF BIAS: Quality assessment was performed based on the National Institutes of Health quality assessment tool for case series studies. RESULTS: Nine hundred fifty-eight individual cases reported from 45 countries were eligible. 88.1% (844/958) were reported from low- or middle-income countries. Corticosteroid use for COVID-19 (78.5%, 619/789) and diabetes (77.9%, 738/948) were common. Diabetic ketoacidosis (p < 0.001), history of malignancy (p < 0.001), underlying pulmonary (p 0.017), or renal disease (p < 0.001), obesity (p < 0.001), hypertension (p 0.040), age (>65 years) (p 0.001), Aspergillus coinfection (p 0.037), and tocilizumab use during COVID-19 (p 0.018) increased the mortality. CAM occurred on an average of 22 days after COVID-19 and 8 days after hospitalization. Diagnosis of mucormycosis in patients with Aspergillus coinfection and pulmonary mucormycosis was made on average 15.4 days (range, 0-35 days) and 14.0 days (range, 0-53 days) after hospitalization, respectively. Cutaneous mucormycosis accounted for <1% of the cases. The overall mortality rate was 38.9% (303/780). CONCLUSION: Mortality of CAM was high, and most reports were from low- or middle-income countries. We detected novel risk factors for CAM, such as older age, specific comorbidities, Aspergillus coinfection, and tocilizumab use, in addition to the previously identified factors.

Mucormycosis in Africa: Epidemiology, diagnosis and treatment outcomes.

Mucorales fungi cause mucormycosis, an invasive and rapidly progressive disease which increasingly affects mostly immunocompromised but also immunocompetent individuals. The objective of this study was to highlight the epidemiology, diagnostic modalities, treatment and overall survival of mucormycosis in Africa. We searched for relevant publications in PubMed, Google Scholar and African Journal Online databases covering the period 1960-2022. A total of 147 articles were identified, of which 66 were included in the review, detailing 408 individual cases from 12 African countries; 330 (80.9%) from North Africa, 63 (15.4%) from Southern Africa, seven (1.7%) from East Africa, seven (1.7%) from West Africa and a single case (0.2%) from Central Africa. The most frequently described clinical forms were rhino-orbital-cerebral (n = 307, 75.2%) and gastrointestinal (n = 51, 12.5%). Diabetes mellitus, COVID-19, malignancies and neutropaenia were the commonest underlying risks in 203 (49.8%), 101 (24.8%), 65 (15.9%) and 53 (13.0%) cases respectively. Most cases, 296 (72.5%) were diagnosed by histopathology. Fungal aetiology was identified in 38 (9.3%), of which the commonest was Rhizopus oryzae/arrhizus (27/38, 71.1%). Of the 408 cases, 334 (81.9%) patients received antifungal therapy, while 244 (59.8%) had surgery. In cases with a specified outcome, survival rate was 59.1% (228/386). Based on case reporting, a substantial burden of mucormycosis occurs in North Africa but the disease is rarely reported in most of the sub-Saharan region. Establishing a comprehensive registry for standardised data collection could improve understanding of the epidemiology of mucormycosis in the region.

Comparative Evaluation of COVID-19 Associated Mucormycosis (CAM) and Non-COVID-19-associated Mucormycosis (non-CAM).

OBJECTIVE: To compare COVID-19 associated mucormycosis cases (CAM) with non-COVID-19 associated mucormycosis (non-CAM) cases followed as in-patients. STUDY DESIGN: Observational Study. PLACE AND DURATION OF STUDY: Department of Infectious Diseases and Clinical Microbiology, Adana City Training and Research Hospital, Health Sciences University (HSU), Adana, Turkey, between January 2018 and March 2022. METHODOLOGY: Patients with a diagnosis of mucormycosis (proven and probable) were dichotomised as COVID-19 associated mucormycosis and non-COVID-19 associated mucormycosis cases. Both groups were compared for underlying malignancy, chemotherapy, antifungal therapy related side effects and overall survival. RESULTS: Of the 35 cases enrolled in the study, 17 (48.6%) had CAM and 18 (51.4%) had non-CAM. A statistically significant difference was detected between non-CAM and CAM cases in terms of haematological malignancy, receiving chemotherapy, and antifungal therapy-related side effects (p=0.019, p=0.019, and p=0.027 respectively). Steroid use was found as a risk factor for the diabetic CAM cases (p<0.0001). The difference between the CAM and non-CAM cases in terms of overall survival was not statistically significant (p=0.088). CONCLUSION: Because of the ongoing COVID-19 pandemic and the increasing number of critical patients, treatment of COVID-19 should be performed cautiously in patients who have the risk of developing CAM, particularly those with diabetes and immunosuppression (haematologic malignancy, receiving steroid or chemotherapy, etc.) and these patients should be monitored closely. KEY WORDS: Mucormycosis, COVID-19, Mucormycosis associated with COVID-19, Diabetes mellitus, Turkey.

Increase in mucormycosis hospitalizations in southeastern Brazil during the COVID-19 pandemic: a 2010-2021 time series.

BACKGROUND: Mucormycosis is a severe invasive fungal disease. During the coronavirus disease 2019 (COVID-19) pandemic, outbreaks have been reported worldwide, but epidemiological studies are still scarce in Brazil. METHODS: We conducted a time-series cohort hospitalization study (2010-2021) in southeastern Brazil. RESULTS: There were 311 cases (85 during the pandemic), with significant (P < 0.05) involvement of patients older than 40 years (84%), white patients (78%), rhinocerebral site (63%), and São Paulo State residents (84%). CONCLUSIONS: Mucormycosis hospitalizations were highly prevalent. Further studies are needed to assess the burden of COVID-19 on mucormycosis in Brazil.

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.

Epidemiology, Risk Factors, Diagnosis and Treatment of Mucormycosis (Black Fungus): A Review.

The COVID-19 pandemic has shown an adverse effect worldwide, but in India, it has been observed during the second wave that people who recovered from COVID-19 infection developed a secondary infection because it grows in tandem with COVID-19 treatment. Meanwhile, news of a new deadly fungus has surfaced known as Mucormycosis (Black fungus). Mucormycosis is a fungal infection that invades the blood vessels and is caused by Mucormycetes, a group of fungi. Due to the post-pandemic effect of COVID-19 many fungal and bacterial diseases have affected the population. The reason behind the frequent development of opportunistic infections like mucormycosis is the use of steroids, oxygen masks, and antibiotics throughout the treatment of critically and severely ill patients with COVID-19. Inhaling filamentous fungi from the natural environment and a lack of supportive care units can be a risk factor for mucormycosis. It is usually found in people who are immunocompromised. Mucormycosis is more common in people with HIV/AIDS, COVID-19, congenital bone marrow disease, viral diseases, malignancies, severe burns, and irregularly or untreated and treated diabetes. This review emphasizes triggers that may precipitate mucormycosis related to corticosteroids, recent epidemiology, and incidence of mucormycosis. The infection was diagnosed and identified using a variety of cutting-edge medical techniques, including clinical diagnosis, histopathology, and serology. Many treatment methods, such as antifungal medications and therapies, have also been successfully used. The mortality rate, however, remains high due to an aggressive surgical excision or debridement and lack of early diagnosis.

The mucormycosis and stroke: The learning curve during the second COVID-19 pandemic.

BACKGROUND: The Angio-invasive Rhino-orbito-cerebral mucormycosis (ROCM) producing strokes is a less explored entity. Our hospital, a stroke-ready one, had an opportunity to manage mucormycosis when it was identified as the nodal center for mucormycosis management. We are sharing our experiences and mistakes in managing the cerebrovascular manifestations of ROCM. METHODS: We conducted a prospective observational study during the second wave of the COVID-19 pandemic from 1st May 2021 to 30th September 2021, where consecutive patients aged more than 18 years with microbiologically confirmed cases of ROCM were included. Clinical details (timing of stroke onset after ROCM symptoms, GCS, NIHSS), imaging findings (ASPECTS, the territory of stroke, the pattern of infarct, hemorrhagic transformation, cavernous sinus thrombosis), angiogram findings, management details (IV thrombolysis), and outcomes (mRS at discharge and duration of hospital stay) were documented. We also compared the demographics, clinical features (NIHSS), radiological findings, treatment details, duration of hospital stay, and functional outcome at the discharge of the ROCM stroke patients with stroke patients without ROCM. RESULTS: Stroke developed in 42% of patients with ROCM, predominantly anterior circulation border zone ischemic infarcts. Strokes occurred after a median of five days from the onset of ROCM symptoms. The most common vessel involved was the ophthalmic artery, followed by the cavernous ICA. We could not thrombolyse ROCM stroke patients. ROCM patients who developed stroke compared with patients without stroke had a more infiltrative fungal infection and higher inflammatory markers. Mucormycosis associated stroke patients had higher in-hospital mortality and poor functional outcomes. T CONCLUSION: Due to delayed recognition of stroke symptoms, none received reperfusion strategies, leading to poor functional outcomes. For early stroke detection, ROCM cases need frequent monitoring and education of patients and their relatives about the ALS acronym (loss of ambulation, limb weakness, and loss of speech).

Risk factors for severe rhino-orbital mucormycosis during its epidemic post-COVID-19 pandemic.

Postsecond wave of COVID-19 pandemic in the year 2021, rhino-orbital mucormycosis (ROM) was seen as an epidemic in the Indian community. Severe ROM disease has poor prognosis and requires a multidisciplinary approach for treatment. Hence, its prevention is better than cure. Studies done during the epidemic assessed predisposing factors, but this was a novel study which focused on assessing risk factors for severe disease of ROM. Ninety-four consecutive patients of ROM admitted at our designated nodal tertiary hospital of North India were enrolled, and data were collected and analyzed. Facial edema was the most common presenting complaint. Subclinical and mild COVID-19 infection was associated with severe ROM. Uncontrolled diabetes mellitus and prophylactic zinc supplementation were other significant risk factors for severe ROM. Public awareness among the general population for the above risk factors can prevent a debilitating disease like severe ROM.

Clinicopathological association of mucormycosis in COVID 19 pandemic.

Context: Coinfection and superadded infections in patients with coronavirus disease 2019 (COVID-19) has been reported on multiple series. The emerging second wave of the pandemic has come with a lot of changes, especially in developing countries like India. One of such changes is sudden, significant rise in mucormycosis cases. Aims: To find out clinicopathological association of invasive mucormycosis with COVID-19 infection status and immunocompromised state. Settings and Design: A cross-sectional study done at a tertiary care centre. Methods and Material: All cases admitted in the dedicated mucormycosis ward between 1-06-2021 and 15-06-2021 were included in the study. The cases were admitted with suspicion of mucormycosis. The histopathological results were correlated with KOH mount and radiological reports. The clinicopathological association of occurrence of mucormycosis in post-covid and non-COVID patients along with other risk factors. Statistical Analysis Used: Odds ratio, chi square test were used to find the association using MS Excel 2010 and SPSS. Results: Thirty-six (81.82%) cases were of the post-COVID status, and 8 cases were non-COVID status. Out of 36 post-COVID patients, 33 (91.67%) showed evidence of invasive mucormycosis and of 8 non-COVIDpatients, 7 had evidence of mucormycosis (odds ratio = 1.57). Out of the total diagnosed cases of mucormycosis, 21 (52.5%) patients were known cases of diabetes mellitus (DM), and 7 (17.5%) cases of newly diagnosed hyperglycemia. Thirty (75%) patients out of 40 had some form of immunocompromised state. This shows statistically significant association of DM and immunocompromised state with the occurrence of mucormycosis in post-COVID patients (chi square value2 = 6.891, P value = 0.008). Twenty-five patients had the history of steroid use during the treatment of COVID-19. Conclusions: The infection with COVID-19 definitely increases the odds of contracting mucormycosis, but most of the cases had diabetes mellitus. So, it is possible that COVID-19 virus predisposes individuals to invasive fungal infection by precipitating DM.

The baneful alliance of COVID-19 and mucormycosis: Histopathological concerns.

Background: Mucormycosis, once a rare fungal disease, has now shown a surge in cases, and its epidemiology in India is intriguing. Rising incidence confers the necessity of defining the demography of the population at risk, early diagnosis, and recommendations for the management of mucormycosis in patients with coronavirus disease (COVID-19) infection. Aims: To study the clinico-epidemological profile, risk factors, and histopathological features of COVID-19-associated Mucormycosis (CAM). Setting and Design: This is a retrospective observational study. Material and Methods: Fifty-six biopsy specimens taken from patients of COVID-19 with clinical suspicion of mucormycosis were included. Results: Diabetes mellitus, corticosteroids, and oxygen therapy were the most common risk factors associated with CAM. The mean duration between the onset of symptoms of COVID-19 and onset of CAM was 25.2 ± 15.3 days. Rhino-orbito-cerebral mucormycosis (ROCM) was present in 24.5% of the cases, with a survival rate of 58.3%. Histopathology showed tissue invasion by branching broad-based, pale, fungal hyphae consistent with mucor in 49 (87.5%) cases. Inflammation was acute neutrophilic type in 61.2% of the patients with a survival rate of 63.33%. The survival rate with chronic non-granulomatous and chronic granulomatous was 100% and 81.8%, respectively. Conclusion: Keeping a high index of suspicion for mucormycosis in COVID-19 by all medical fraternities of the health community in the existence of risk factors is the need of the hour for prompt diagnosis. Biopsy of antral necrotic tissue should be performed immediately after suspicion for histopathological study to confirm the diagnosis of mucormycosis and predict prognosis depending on the type of inflammation incited, fungal morphology, load, and necrosis.

Pharmacovigilance study of amphotericin B for mucormycosis in post-COVID and non-COVID patients at a tertiary care hospital in Eastern India.

BACKGROUND: Mucormycosis is a rare but serious fungal infection which has dramatically increased in post-COVID patients. There is a paucity of safety data on amphotericin B (amphoB) used for mucormycosis treatment. OBJECTIVES: The objective of this prospective, observational, active safety surveillance study was to evaluate the safety profile of amphoB in a cohort of hospitalized patients who were on the drug for suspected mucormycosis. MATERIALS AND METHODS: All suspected adverse drug reactions (ADRs) in hospitalized mucormycosis patients who had received amphoB were analyzed. The nature, severity, outcome of the ADRs were recorded and analyzed. RESULTS: Of the 77 patients enrolled, 70% had documented history of prior COVID-19 infection. 96% had comorbidities, the most common being diabetes. Majority received conventional amphotericin B deoxycholate formulation. 97% experienced at least one suspected ADR and the median ADR/patient was 3. Out of 214 ADRs, 91 were serious but there were no ADR-related deaths. The most common ADRs were hypokalemia (31.78%), infusion-related reactions (22.43%), and anemia (17.29%). Thirty-three patients had serum potassium <2.5 mEq/L, while 11 had serum magnesium <1.25 mg/dL. Doubling of pretreatment creatinine level was noted in 15 patients. Seventy percent ADRs were of "possible" category as per the World Health Organization Uppsala Monitoring Centre categorization. CONCLUSION: AmphoB deoxycholate use in mucormycosis patients was associated with a high incidence of electrolyte abnormalities and infusion-related reactions. All ADRs subsided with medical management and none were fatal. The safety data generated from this study may be useful in resource-limited settings where the far more expensive liposomal formulation is not being used.

Genetic Manipulation in Mucorales and New Developments to Study Mucormycosis.

The study of the Mucoralean fungi physiology is a neglected field that the lack of effective genetic tools has hampered in the past. However, the emerging fungal infection caused by these fungi, known as mucormycosis, has prompted many researchers to study the pathogenic potential of Mucorales. The main reasons for this current attraction to study mucormycosis are its high lethality, the lack of effective antifungal drugs, and its recent increased incidence. The most contemporary example of the emergence character of mucormycosis is the epidemics declared in several Asian countries as a direct consequence of the COVID-19 pandemic. Fortunately, this pressure to understand mucormycosis and develop new treatment strategies has encouraged the blossoming of new genetic techniques and methodologies. This review describes the history of genetic manipulation in Mucorales, highlighting the development of methods and how they allowed the main genetic studies in these fungi. Moreover, we have emphasized the recent development of new genetic models to study mucormycosis, a landmark in the field that will configure future research related to this disease.