Invasive fungal infections in patients with haematological malignancies at the University Hospital of Reunion Island (2018-2022): An observational study.

Invasive fungal infections are a serious complication for haematology patients. However, there is no study on this subject in Reunion Island. The aim of this study was to estimate the incidence of invasive fungal infections in patients with haematological malignancies at the University Hospital of Reunion Island. We conducted a descriptive and ambispective study. We included any patient with haematological malignancy presenting with a putative, possible, probable, or proven invasive fungal infection, defined as per the criteria of the European Organisation for Research and Treatment of Cancer/Mycoses Study Group 2019, from January 2018 to December 2022. Data were collected from medical records and identified by ICD-10 coding and laboratory data. Eighty-nine invasive fungal infections were diagnosed in 76 patients. The 5-year incidence rate of invasive fungal infections was 1.7 per 100 person-years (95% Confidence Interval (CI) 1.3-2). Invasive aspergillosis was the most common infection (35/89, 39%), followed by invasive candidiasis (33/89, 37%), mucormycosis (7/89, 8%), and pneumocystosis (7/89, 8%). Most infections occurred in patients with acute myeloid leukaemia (32/89, 36%) and lymphoma (26/89, 29%). Six-month mortality was higher for mucormycosis (71%) than for aspergillosis (34%) and invasive candidiasis (33%). The incidence and distribution of fungal infections in haematology patients were similar to European cohorts, albeit with more mucormycosis, less pneumocystis, and a high proportion of Candida parapsilosis in candidemia.

Among 76 patients, the 5-year incidence rate of invasive fungal infections in haematological patients at Reunion Island's University Hospital was 1.7% (95% CI 1.3­2). Aspergillosis (39%) and candidiasis (37%) were the predominant ones. The findings align with European cohorts, though with some distinct characteristics.

Invasive fungal infections in patients with acute leukemia: A retrospective cohort study at a tertiary-care hospital.

Invasive fungal infection (IFI) is an important cause of morbidity and mortality in acute leukemia patients. In the past few decades, the incidence of IFI has dramatically increased. Nevertheless, the management of IFI has become more complicated owing to changes in the epidemiology of fungal diseases and therapeutic regimens. Therefore, it is important to establish an appropriate strategy for centers that provide the diagnosis and treatment of acute leukemia patients based on scientific data and with available resources. In this study we investigated the incidence of IFI, pathogens, the use of diagnostic methods, and risk factors for IFI in acute leukemia patients over a 17-year period. A total of 502 acute leukemia patients (male/female: 57%/43%, mean age: 57.7 ±â€…15.5 years) hospitalized at adult and oncology hospitals between 2003 and 2020 were reviewed retrospectively. The incidence of proven and probable IFI was 13.2% (33.1%, when possible cases were included). The most common IFI was aspergillosis (49 patients, 9.7%), followed by candidemia, mucormycosis, and Pneumocystis jirovecii pneumonia. The galactomannan antigen test was positive in the serum of 39 (23.5%) patients and in bronchoalveolar lavage (BAL) fluid in 6 (3.6%) patients. Thirteen (7.8%) sputum cultures (11 Aspergillus spp. and 2 Candida spp.) and 4 (2.4%) BAL fluid (1 Aspergillus spp., 2 Candida spp., 1 P jirovecii) were positive for a fungal pathogen. Neutropenia, intensive care unit (ICU) follow-up and mechanical ventilation (MV) increased the risk of IFI by 3.5, 2.5, and 1.8 times, respectively. The median survival was 5 (range: 1.9-8) months. ICU follow-up shortened the survival by 12 months and increased the death risk by 2.49-fold. MV shortened survival by 57 months and increased the death risk by 3.82-fold. IFI remains a significant contributor to the morbidity and mortality in acute leukemia patients. Pulmonary involvement is the most common site. Neutropenia, ICU follow-up and MV are associated with an increased risk for IFI and mortality. We recommend in the IFI approach, to be aware of IFI in patients receiving intensive chemotherapy and/or recipients of hematopoietic stem cell transplantation, and to evaluate with microbiological, serological and radiological tests during the clinical follow-up.

Longitudinal Epidemiology of Mucormycosis Within the Veterans Health Administration: A Retrospective Cohort Study Over a 20-Year Period.

BACKGROUND: Mucormycosis is a rare but critical infection. Due to its rarity, there is scarce evidence about the longitudinal changes in the epidemiology of mucormycosis in the US. OBJECTIVES: We investigated the longitudinal epidemiology, detailed clinical characteristics, treatment and outcomes of patients with mucormycosis within the US Veterans Health Administration (VHA) over 20-year period. PATIENTS/METHODS: All adult patients who were admitted to an acute-care hospital with a diagnosis of mucormycosis within the VHA from January 2003 to December 2022. RESULTS: Our study included 201 patients from 68 hospitals. Incidence rates of mucormycosis increased from 1.9 per 100,000 hospitalisations in 2003 to 3.3 per 100,000 hospitalisations in 2022, with a peak incidence at 5.9 per 100,000 hospitalisations in 2021, when the Delta wave of COVID-19 hit the US. Rhino-orbital (37.3%) and pulmonary mucormycosis (36.8%) were the most common types of infection. Diabetes mellitus (59.1%) and leukaemia (28.9%) were most common comorbidities predisposing to mucormycosis. Use of posaconazole or isavuconazole increased over time. The 90-day and 1-year mortalities were 35.3% and 49.8%, respectively. The mortality was lower in more recent years (2013-2017, 2018-2022) compared to earlier years (2003-2007). Age ≥65 (adjusted odds ratio [aOR]: 3.47, 95% CI 1.59-7.40), leukaemia as a comorbidity (aOR: 2.66, 95% CI 1.22-5.89) and central nervous system infection (aOR: 10.59, 95% CI 2.81-44.57) were significantly associated with higher 90-day mortality. CONCLUSIONS: Our longitudinal cohort study suggests the increasing incidence rates but lower mortality of mucormycosis over this 20-year period.

Post COVID-19 mucormycosis in critical care settings: A prospective cohort study in a tertiary care center in Egypt.

BACKGROUND: The emergence of mucormycosis as a life-threatening fungal infection after the coronavirus disease of 2019 (COVID-19) is a major concern and challenge, but there is limited information on the risk factors for mortality in patients. METHODS: We conducted a prospective cohort study from May 2021 to April 2022 to determine the in-hospital outcomes of post-COVID-19 mucormycosis during the intensive care unit (ICU) stay. The sample of the study was collected as consecutive sampling using all accessible patients in the study period. The Statistical Package for Social Sciences (SPSS), version 25 (IBM, Chicago, Illinois, USA) was used for statistical analysis. RESULTS: Among 150 patients with post-COVID-19 mucormycosis, the majority had a primary sinus infection (86.0 %), while 11.3 % had both sinus and ocular infections, and 2.7 % had sinus and cutaneous infections. Around 21 % (n = 31) of patients deceased after staying in the ICU for a median (range) of 45.0 (10.0-145.0) days. The majority of the patients who deceased had pneumonia patches on computed tomography (CT) (90.3 %) while none of the patients who were discharged had pneumonia patches (p < 0.001). The deceased group had higher rates of pulmonary embolism (93.5 %) compared to the surviving groups (21.8 %). In a multivariate Cox regression analysis, the risk of death was higher in older patients above 60 years old (hazard ratio (95 %CI): 6.7 (1.73-15.81)), increase among patient with history of steroid administration (hazard ratio (95 %CI): 5.70 (1.23-10.91)), who had facial cutaneous infection with mucormycosis (hazard ratio (95 %CI): 8.76 (1.78-25.18)), patients with uncontrolled diabetes (hazard ratio (95 %CI): 10.76 (1.78, 65.18)), and total leukocytic count (TLC>10 ×103 mcL) (hazard ratio (95 %CI): 10.03 (3.29-30.61)). CONCLUSIONS: Identifying high-risk patients especially old diabetic patients with corticosteroid administration and detecting their deterioration quickly is crucial in reducing post-COVID-19 mucormycosis mortality rates, and these factors must be considered when developing treatment and quarantine strategies.

Clinical characteristics and mortality of mucormycosis in hematological malignancies: a retrospective study in Eastern China.

BACKGROUND: Mucormycosis is a significant cause of morbidity and mortality in patients with hematological malignancies, but its characteristics are not fully understood. This study aimed to gain a better understanding of the clinical features of mucormycosis in patients with hematological malignancies in eastern China. METHODS: A single-center retrospective analysis was conducted on the demographic profile, microbiology, management, and 90-day mortality of mucormycosis patients with hematological malignancies between 2018 and 2023. RESULTS: A total of 50 cases were included in the study, consisting of 11 proven and 39 probable cases of mucormycosis. The median age of the patients was 39.98 ± 18.52 years, with 52% being male. Among the cases, 46% had acute myeloid leukemia (AML), 16% had acute lymphoblastic leukemia (ALL), and 16% had myelodysplastic syndrome. The most common manifestations of mucormycosis were pulmonary (80%), disseminated (16%), and rhinocerebral (4%). The diagnosis was confirmed through histology, culture, microscopy, and molecular diagnostic techniques. The most commonly identified fungal species were Cunninghamella (40%), Rhizopus (26%), and Rhizomucor (22%). Treatment involved antifungals in 84% of cases and surgery in 10% of cases. The 90-day mortality rate was 76%. Logistic regression analysis revealed that treatment with amphotericin B and surgery was associated with improved survival, while neutropenia and administration of voriconazole prior to diagnosis was associated with higher mortality. CONCLUSIONS: Mucormycosis continues to have a high mortality rate in patients with hematological malignancies. Early diagnosis using various techniques, including molecular biology, along with the appropriate use of amphotericin B and surgery when possible, is vital for the successful treatment of mucormycosis.

Clinical Characteristics, Prognosis Factors and Metagenomic Next-Generation Sequencing Diagnosis of Mucormycosis in patients With Hematologic Diseases.

INTRODUCTION: New diagnostic methods and antifungal strategies may improve prognosis of mucormycosis. We describe the diagnostic value of metagenomic next⁃generation sequencing (mNGS) and identify the prognostic factors of mucormycosis. METHODS: We conducted a retrospective study of hematologic patients suffered from mucormycosis and treated with monotherapy [amphotericin B (AmB) or posaconazole] or combination therapy (AmB and posaconazole). The primary outcome was 84-day all-cause mortality after diagnosis. RESULTS: Ninety-five patients were included, with "proven" (n = 27), "probable" (n = 16) mucormycosis confirmed by traditional diagnostic methods, and "possible" (n = 52) mucormycosis with positive mNGS results. The mortality rate at 84 days was 44.2%. Possible + mNGS patients and probable patients had similar diagnosis processes, overall survival rates (44.2% vs 50.0%, p = 0.685) and overall response rates to effective drugs (44.0% vs 37.5%, p = 0.647). Furthermore, the median diagnostic time was shorter in possible + mNGS patients than proven and probable patients (14 vs 26 days, p < 0.001). Combination therapy was associated with better survival compared to monotherapy at six weeks after treatment (78.8% vs 53.1%, p = 0.0075). Multivariate analysis showed that combination therapy was the protective factor (HR = 0.338, 95% CI: 0.162-0.703, p = 0.004), though diabetes (HR = 3.864, 95% CI: 1.897-7.874, p < 0.001) and hypoxemia (HR = 3.536, 95% CI: 1.874-6.673, p < 0.001) were risk factors for mortality. CONCLUSIONS: Mucormycosis is a life-threatening infection. Early management of diabetes and hypoxemia may improve the prognosis. Exploring effective diagnostic and treatment methods is important, and combination antifungal therapy seems to hold potential benefits.

Risk Factors of COVID-19 associated mucormycosis in Iranian patients: a multicenter study.

BACKGROUND: To evaluate the demographic, clinical, and prognostic characteristics of patients diagnosed with COVID-19-associated mucormycosis (CAM) in Iranian patients. METHODS: This prospective observational study was conducted in 8 tertiary referral ophthalmology centers in different provinces of Iran during the fifth wave of the COVID-19 pandemic. All patients were subjected to complete history taking and comprehensive ophthalmological examination and underwent standard accepted treatment strategy based on the disease stage. RESULTS: Two hundred seventy-four CAM patients (most were males (150, 54.7%)) with a mean age of 56.8 ± 12.44 years were enrolled. Patients with a history of cigarette smoking (Adjusted Odds Ratio (AOR) = 4.36), Intensive Care Unit admission (ICU) (AOR = 16.26), higher stage of CAM (AOR = 2.72), and receiving endoscopic debridement and transcutaneous retrobulbar amphotericin B (AOR = 3.30) had higher odds of mortality. History of taking systemic corticosteroids during COVID-19 was significantly associated with reduced odds of mortality (AOR = 0.16). Generalized Estimating Equations analysis showed that the visual acuity of deceased patients (LogMAR: 3.71, 95% CI: 3.04-4.38) was worse than that of patients who were discharged from the hospital (LogMAR: 2.42, 95% CI: 2.16-2.68) (P < 0.001). CONCLUSIONS: This study highlights significant risk factors for mortality in patients with CAM, such as cigarette smoking, ICU admission, advanced CAM stages, receiving transcutaneous retrobulbar amphotericin B and worser visual acuity. Conversely, a history of systemic corticosteroid use during COVID-19 was linked to reduced mortality. These findings underscore the critical need for early identification and targeted interventions for high-risk CAM patients to improve clinical outcomes.

Number of sinus procedures reduces inpatient mortality for invasive fungal rhinosinusitis.

OBJECTIVES: To evaluate surgical outcomes of invasive fungal rhinosinusitis MATERIALS AND METHODS: The National Inpatient Sample Database (2000-2015 Q3) was queried for patients with a diagnosis of aspergillosis and/or mucormycosis and a diagnosis of acute sinusitis using the International Classification of Diseases, Ninth Edition. Factors associated with inpatient mortality were then identified with multivariate logistic regression. RESULTS: 514 adult patients with a median age of 57.0 years were identified, of which 231 (44.9 %) underwent sinus surgery. Surgical patients had a longer length of stay (17.0 vs 9.0 days, p < 0.001) and higher total charges ($139,762.00 vs $57,945.00, p < 0.001). The number of sinus procedures was associated with reduced odds of inpatient mortality (OR 0.69; p < 0.001) in multivariate analysis. Hypertension (OR 0.34, p = 0.002) and chronic kidney disease (OR 0.23, p = 0.034) were associated with reduced odds of inpatient mortality. Total number of procedures (OR 1.24; p = 0.002), mucormycosis (OR 2.75, p = 0.002), age (OR 1.03, p = 0.006) and acid-base disorders (OR 2.85, p = 0.012) were associated with increased odds of inpatient mortality. CONCLUSION: This represents the first large scale study to evaluate outcomes for invasive fungal rhinosinusitis. These findings suggest the odds of inpatient mortality decrease with greater extent of sinus surgery performed. The potentially protective roles of hypertension and chronic kidney disease should be evaluated in future research.

Observational study on the clinical profile and treatment outcome on long-term follow-up of COVID-19 associated mucormycosis.

MATERIALS AND METHODS: Patients diagnosed with COVID-19 associated mucormycosis were followed up for 6 months to study the clinical profile, readmissions, long-term treatment outcome and the mortality rate. RESULTS: Among 37 patients with COVID-19 associated mucormycosis, the mortality rate was 33.3 %, 42.9% and 100 % among patients with mild, moderate and severe COVID-19 infection. One month after discharge, among the 20 patients who survived, 10 (50 %) patients had worsening symptoms and required readmission. Nine patients required readmission for amphotericin and 1 patient was admitted for surgical intervention. On follow-up at 1 month, 30 % (6/20) patients became asymptomatic. However, at 3 months, 45 % (9/20) of the patients were asymptomatic. At 6 months of follow-up, 80 % (16/20) were asymptomatic. At 6 months, one each had residual abnormalities like visual loss in one eye, visual field deficit, change in voice and residual weakness of the limbs along with cranial nerve paresis. CONCLUSION: The follow-up study revealed that a significant number of patients required readmission within the first month, but most of the patients became asymptomatic by 6 months. The readmission rate was higher in patients who received a shorter duration of amphotericin.

Mucorales: A systematic review to inform the World Health Organization priority list of fungal pathogens.

The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list (FPPL). This systematic review aimed to evaluate the epidemiology and impact of invasive fungal disease due to Mucorales. PubMed and Web of Science were searched to identify studies published between January 1, 2011 and February 23, 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 24 studies were included. Mortality rates of up to 80% were reported. Antifungal susceptibility varied across agents and species, with the minimum inhibitory concentrations lowest for amphotericin B and posaconazole. Diabetes mellitus was a common risk factor, detected in 65%-85% of patients with mucormycosis, particularly in those with rhino-orbital disease (86.9%). Break-through infection was detected in 13.6%-100% on azole or echinocandin antifungal prophylaxis. The reported prevalence rates were variable, with some studies reporting stable rates in the USA of 0.094-0.117/10 000 discharges between 2011 and 2014, whereas others reported an increase in Iran from 16.8% to 24% between 2011 and 2015. Carefully designed global surveillance studies, linking laboratory and clinical data, are required to develop clinical breakpoints to guide antifungal therapy and determine accurate estimates of complications and sequelae, annual incidence, trends, and global distribution. These data will provide robust estimates of disease burden to refine interventions and better inform future FPPL.

Factors influencing mortality in COVID-19-associated mucormycosis: The international ID-IRI study.

The emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), triggered a global pandemic. Concurrently, reports of mucormycosis cases surged, particularly during the second wave in India. This study aims to investigate mortality factors in COVID-19-associated mucormycosis (CAM) cases, exploring clinical, demographic, and therapeutic variables across mostly Asian and partly African countries. A retrospective, cross-sectional analysis of CAM patients from 22 medical centers across eight countries was conducted, focusing on the first 3 months post-COVID-19 diagnosis. Data collected through the ID-IRI included demographics, comorbidities, treatments, and outcomes. A total of 162 CAM patients were included. The mean age was 54.29 ± 13.04 years, with 54% male. Diabetes mellitus (85%) was prevalent, and 91% had rhino-orbital-cerebral mucormycosis. Surgical debridement was performed in 84% of the cases. Mortality was 39%, with advanced age (hazard ratio [HR] = 1.06, [P < .001]), rituximab use (HR = 21.2, P = .05), and diabetic ketoacidosis (HR = 3.58, P = .009) identified as risk factors. The mortality risk increases by approximately 5.6% for each additional year of age. Surgical debridement based on organ involvement correlated with higher survival (HR = 8.81, P < .001). The utilization of rituximab and diabetic ketoacidosis, along with advancing age, has been associated with an increased risk of mortality in CAM patients. A combination of antifungal treatment and surgical intervention has demonstrated a substantial improvement in survival outcomes.

Over a third of patients who developed mucormycosis after COVID-19 died. Older people, those on specific immunosuppressive treatments, and those with diabetic ketoacidosis had a higher risk of death. However, undergoing surgery as part of treatment significantly improved survival.

Invasive Fungal Sinusitis and Its Orbital Morbidity in Pediatric Population: A Strategic Treatment Algorithm and Outcomes.

BACKGROUND: Invasive fungal sinusitis, particularly mucormycosis, presents a significant clinical challenge, especially in pediatric populations. This retrospective epidemiologic study aimed to investigate the clinical characteristics, risk factors and outcomes associated with this rare but severe condition, with a focus on orbital morbidity. METHODS: Clinical data of 12 pediatric patients diagnosed with invasive fungal sinusitis between 2021 and 2023 were retrospectively analyzed. Diagnosis involved microbiological and histopathologic examinations, alongside radiologic imaging. Treatment comprised surgical intervention and antifungal therapy, with a detailed evaluation of orbital involvement. Statistical analysis included descriptive statistics and logistic regression. RESULTS: Predominantly affecting males, the median age of the patients was 8 years. Common symptoms included orbital swelling and impaired vision. Imaging revealed characteristic features of invasive fungal sinusitis, including fat stranding and bone erosions. Orbital involvement was extensive, with poor visual outcomes observed in several cases. Surgical debridement and antifungal therapy, including transcutaneous retrobulbar Amphotericin B, were administered. Risk factors associated with poor orbital outcomes included duration of diabetes and glycated hemoglobin levels. Mortality rate stood at 22.2%. CONCLUSIONS: Early diagnosis, aggressive surgical intervention and combined antifungal therapy are essential for improving outcomes. Timely intervention showed stabilization of the orbital disease and better outcomes in pediatric patients. Further research with larger sample sizes is warranted to better understand and address this serious condition.

Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

Dynamics and prognostic value of plasma cell-free DNA PCR in patients with invasive aspergillosis and mucormycosis.

Aspergillus species and Mucorales agents are the primary etiologies of invasive fungal disease (IFD). Biomarkers that predict outcomes are needed to improve care. Patients diagnosed with invasive aspergillosis and mucormycosis using plasma cell-free DNA (cfDNA) PCR were retested weekly for 4 weeks. The primary outcome included all-cause mortality at 6 weeks and 6 months based on baseline cycle threshold (CT) values and results of follow-up cfDNA PCR testing. Forty-five patients with Aspergillus and 30 with invasive Mucorales infection were retested weekly for a total of 197 tests. Using the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSG) criteria, 30.7% (23/75), 25.3% (19/75), and 38.7% (29/75) had proven, probable, and possible IFD, respectively. In addition, 97.3% (73/75) were immunocompromised. Baseline CT increased significantly starting at week 1 for Mucorales and week 2 for Aspergillus. Aspergillosis and mucormycosis patients with higher baseline CT (CT >40 and >35, respectively) had a nonsignificantly higher survival rate at 6 weeks, compared with patients with lower baseline CT. Mucormycosis patients with higher baseline CT had a significantly higher survival rate at 6 months. Mucormycosis, but not aspergillosis patients, with repeat positive cfDNA PCR results had a nonsignificantly lower survival rate at 6 weeks and 6 months compared with patients who reverted to negative. Aspergillosis patients with baseline serum Aspergillus galactomannan index <0.5 and <1.0 had significantly higher survival rates at 6 weeks when compared with those with index ≥0.5 and ≥1.0, respectively. Baseline plasma cfDNA PCR CT can potentially be used to prognosticate survival in patients with invasive Aspergillus and Mucorales infections. IMPORTANCE: We show that Aspergillus and Mucorales plasma cell-free DNA PCR can be used not only to noninvasively diagnose patients with invasive fungal disease but also to correlate the baseline cycle threshold with survival outcomes, thus potentially allowing the identification of patients at risk for poor outcomes, who may benefit from more targeted therapies.

Resolving the equation between mucormycosis and COVID-19 disease.

The COVID-19 patients, both infected and recovered are rapidly contracting mucormycetes infections due to the 'Mucorales' order, under Zygomycetes class of fungi. The mucorales fungi commonly known to exist in our natural surroundings including soil, but the frequency of incidences was never rampant. This sudden spike in infections, is locally known as 'black fungus,' and is affecting various organs, including- eyes, sinuses, nose, brain, skin, intestine, lungs, etc. The severity of situation is ascertainable from the fact that, in certain cases surgical eye/jaws removal persists as the only viable option to avert mortality, as therapeutic interventions are limited. This epidemic situation intrigued experts to investigate the probable reason behind this unpredicted escalation in reported cases, including in recuperated COVID-19 patients, as person-to-person spread of infection is not common. The comparison of physiological parameters in healthy and COVID-19 afflicted patients highlights that the underlying conditions including diabetes mellitus, steroidal therapy, lymphopenia (decreased CD4+ and CD8+ lymphocytes), deregulated cytokine release storm, elevated free iron levels (hemosiderosis) in blood and insulin insensitivity are playing major roles in deteriorating conditions in rarely pathogenic fungal infections. This review is an attempt to explain the rationalities that makes people vulnerable to mucormycetes infection.

A systematic review on SARS-CoV-2-associated fungal coinfections.

A severe pandemic of Coronavirus Disease (COVID-19) has been sweeping the globe since 2019, and this time, it did not stop, with frequent mutations transforming into virulent strains, for instance, B.1.1.7, B.1.351, and B.1.427. In recent months, a fungal infection, mucormycosis has emerged with more fatal responses and significantly increased mortality rate. To measure the severity and potential alternative approaches against black fungus coinfection in COVID-19 patients, PubMed, Google Scholar, World Health Organization (WHO) newsletters, and other online resources, based on the cases reported and retrospective observational analysis were searched from the years 2015-2021. The studies reporting mucormycosis with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) coinfection and/or demonstrating potential risk factors, such as a history of diabetes mellitus or suppressed immune system were included, and reports published in non-English language were excluded. More than 20 case reports and observational studies on black fungus coinfection in COVID-19 patients were eligible for inclusion. The results indicated that diabetes mellitus, hyperglycemic, and immunocompromised COVID-19 patients with mucormycosis were at a higher risk. We found that it was prudent to assess the potential risk factors and severity of invasive mycosis via standardized diagnostic and clinical settings. Large-scale studies need to be conducted to identify early biomarkers and optimization of diagnostic methods has to be established per population and geographical variation. This will not only help clinicians around the world to detect the coinfection in time but also will prepare them for future outbreaks of other potential pandemics.

Case Report: Rhino-orbital Mucormycosis Related to COVID-19: A Case Series Exploring Risk Factors.

There has been a surge of rhino-orbital mucormycosis cases in India in the wake of the second wave of the COVID-19 pandemic. It has been widely suggested that dysglycemia resulting from diabetes which is a common comorbidity in COVID-19 patients, and indiscriminate steroid use has resulted in this surge. We report a series of 13 cases of rhino-orbital mucormycosis in COVID-19 patients admitted to our center between mid-April and early June 2021. The cases showed a male preponderance, two patients had loss of vision, and four of them showed intracranial extension of disease. Twelve patients had received steroids and 12 had preexisting or newly diagnosed diabetes, both steroid use and diabetes being the most common identified risk factors. Considering other possible risk factors, immunosuppressed state, antiviral or ayurvedic (Indian traditional) medications, and oxygen therapy were not associated with a definite risk of mucormycosis, because they were not present uniformly in the patients. We propose that COVID-19 itself, through molecular mechanisms, predisposes to mucormycosis, with other factors such as dysglycemia or steroid use increasing the risk.

COVID-19 associated mucormycosis: A Descriptive Multisite Study from India.

BACKGROUND AND AIMS: Mucormycosis is an invasive fungal infection and carries a significant morbidity and mortality. A number of cases of mucormycosis have been reported in association with COVID-19. In this study, a consortium of clinicians from various parts of India studied clinical profile of COVID-19 associated mucormycosis (CAM) and this analysis is presented here. METHODS: Investigators from multiple sites in India were involved in this study. Clinical details included the treatment and severity of COVID-19, associated morbidities, as well as the diagnosis, treatment and prognosis of mucormycosis. These data were collected using google spreadsheet at one centre. Descriptive analysis was done. RESULTS: There were 115 patients with CAM. Importantly, all patients had received corticosteroids. Diabetes was present in 85.2% of patients and 13.9% of patients had newly detected diabetes. The most common site of involvement was rhino-orbital. Mortality occurred in 25 (21.7%) patients. On logistic regression analysis, CT scan-based score for severity of lung involvement was associated with mortality. CONCLUSION: Universal administration of corticosteroids in our patients is notable. A large majority of patients had diabetes, while mortality was seen in ∼1/5th of patients, lower as compared to recently published data.

Rhino-orbital-cerebral-mucormycosis in COVID-19: A systematic review.

Since the onset of COVID-19 pandemic, parallel opportunistic infections have also been emerging as another disease spectrum. Among all these opportunistic infection, mucormycosis has become a matter of concern with its rapid increase of cases with rapid spread as compared to pre-COVID-19 era. Cases have been reported in post-COVID-19-related immune suppression along with the presence of comorbidity which adds on the deadly outcome. There is no systematic review addressing the issue of COVID-19-associated mucormycosis. This is the first systematic review of published studies of mucormycosis associated with COVID-19. The aim was to analyze the real scenario of the disease statement including all the published studies from first November 2019 to 30th June to analyze the contemporary epidemiology, clinical manifestations, risk factor, prognosis, and treatment outcome of COVID-19 associated rhino-orbito-cerebral-mucormycosis. A comprehensive literature search was done in following databases, namely, PubMed, Google Scholar, Scopus, and EMBASE using keywords mucormycosis, rhino orbital cerebral mucormycosis, COVID-19, and SARS-CoV-2 (from November 01, 2019 to June 30, 2021). Our study shows that, while corticosteroids have proved to be lifesaving in severe to critical COVID-19 patients, its indiscriminate use has come with its price of rhino-orbito-cerebral mucormycosis epidemic, especially in India especially in patients with preexisting diabetes mellitus with higher mortality. Corticosteroid use should be monitored and all COVID-19 patients should be closely evaluated/monitored for sequelae of immunosuppression following treatment.