Choanephora infundibulifera Rhinosinusitis in Man with Acute Lymphoblastic Leukemia, Tennessee, USA.

Choanephora infundibulifera is a member of the Mucorales order of fungi. The species is associated with plants as a saprophyte or parasite and may be responsible for spoilage or disease but is an uncommon cause of human infection. We describe C. infundibulifera rhinosinusitis in a young man with leukemia in Tennessee, USA.

Ibrexafungerp is efficacious in a neutropenic murine model of pulmonary mucormycosis as monotherapy and combined with liposomal amphotericin B.

Ibrexafungerp (formerly SCY-078) is the first member of the triterpenoid class that prevents the synthesis of the fungal cell wall polymer ß-(1,3)-D-glucan by inhibiting the enzyme glucan synthase. We evaluated the in vivo efficacy of ibrexafungerp against pulmonary mucormycosis using an established murine model. Neutropenic mice were intratracheally infected with either Rhizopus delemar or Mucor circinelloides. Treatment with placebo (diluent control), ibrexafungerp (30 mg/kg, PO BID), liposomal amphotericin B (LAMB 10 mg/kg IV QD), posaconazole (PSC 30 mg/kg PO QD), or a combination of ibrexafungerp plus LAMB or ibrexafungerp plus PSC began 16 h post-infection and continued for 7 days for ibrexafungerp or PSC and through day 4 for LAMB. Ibrexafungerp was as effective as LAMB or PSC in prolonging median survival (range: 15 days to >21 days) and enhancing overall survival (30%-65%) vs placebo (9 days and 0%; P < 0.001) in mice infected with R. delemar. Furthermore, median survival and overall percent survival resulting from the combination of ibrexafungerp plus LAMB were significantly greater compared to all monotherapies (P ≤ 0.03). Similar survival results were observed in mice infected with M. circinelloides. Monotherapies also reduce the lung and brain fungal burden by ~0.5-1.0log10 conidial equivalents (CE)/g of tissue vs placebo in mice infected with R. delemar (P < 0.05), while a combination of ibrexafungerp plus LAMB lowered the fungal burden by ~0.5-1.5log10 CE/g compared to placebo or any of the monotherapy groups (P < 0.03). These results are promising and warrant continued investigation of ibrexafungerp as a novel treatment option against mucormycosis.

Myo5B plays a significant role in the hyphal growth and virulence of the human pathogenic fungus Mucor lusitanicus.

Mucormycosis is an emerging and deadly invasive fungal infection caused by fungi belonging to the Mucorales order. We investigated the myosin superfamily, which encompasses diverse actin-based motor proteins with various cellular functions. Specifically, the role of the Myo5B (ID 179665) protein from the myosin class V family in Mucor lusitanicus was explored by generating silencing phenotypes and null mutants corresponding to the myo5B gene. Silencing fungal transformants exhibited a markedly reduced growth rate and a nearly complete absence of sporulation compared to the wild-type strain. The myo5BΔ null mutant strain displayed atypical characteristics, including abnormally short septa and inflated hyphae. Notably, there were a majority of small yeast-like cells instead of filamentous hyphae in the mutant. These yeast-like cells cannot germinate normally, resulting in a loss of polarity. In vivo virulence assays conducted in the Galleria mellonella invertebrate model revealed that the myo5BΔ mutant strain was avirulent. These findings shed light on the crucial contributions of the Myo5B protein to the dimorphism and pathogenicity of M. lusitanicus. Therefore, the myosin V family is a potential target for future therapeutic interventions aimed at treating mucormycosis.

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.

Deep-AFPpred: identifying novel antifungal peptides using pretrained embeddings from seq2vec with 1DCNN-BiLSTM.

Fungal infections or mycosis cause a wide range of diseases in humans and animals. The incidences of community acquired; nosocomial fungal infections have increased dramatically after the emergence of COVID-19 pandemic. The increase in number of patients with immunodeficiency / immunosuppression related diseases, resistance to existing antifungal compounds and availability of limited therapeutic options has triggered the search for alternative antifungal molecules. In this direction, antifungal peptides (AFPs) have received a lot of interest as an alternative to currently available antifungal drugs. Although the AFPs are produced by diverse population of living organisms, identifying effective AFPs from natural sources is time-consuming and expensive. Therefore, there is a need to develop a robust in silico model capable of identifying novel AFPs in protein sequences. In this paper, we propose Deep-AFPpred, a deep learning classifier that can identify AFPs in protein sequences. We developed Deep-AFPpred using the concept of transfer learning with 1DCNN-BiLSTM deep learning algorithm. The findings reveal that Deep-AFPpred beats other state-of-the-art AFP classifiers by a wide margin and achieved approximately 96% and 94% precision on validation and test data, respectively. Based on the proposed approach, an online prediction server is created and made publicly available at https://afppred.anvil.app/. Using this server, one can identify novel AFPs in protein sequences and the results are provided as a report that includes predicted peptides, their physicochemical properties and motifs. By utilizing this model, we identified AFPs in different proteins, which can be chemically synthesized in lab and experimentally validated for their antifungal activity.

Current treatments against mucormycosis and future directions.

Mucormycosis (previously called zygomycosis) is a serious but rare fungal infection caused by a group of fungi belonging to the order Mucorales. These molds exist throughout the environment and generally do not cause serious problems in humans. Mucormycosis mainly affects individuals who are immunocompromised. The clinical manifestations of mucormycosis are wide-ranging; they include sinusitis (pansinusitis, rhino-orbital, or rhino-cerebral) as well as cutaneous, gastrointestinal, pulmonary, and disseminate infections. Many uncertainties remain regarding how to control these infections despite the recent addition of triazoles to the antifungal arsenal for treating this infection. Currently, lipid formulations of amphotericin B have become the standard treatment for mucormycosis due to their efficiency. Moreover, a growing body of data supports the need for surgical excision of infected and/or necrosed tissue whenever practical. In this mini review, the current status of treatment options for mucormycosis and recent studies of novel therapeutic options will be presented.

Metagenomic insights into fungal community composition of the nasopharyngeal region of COVID-19 associated mucormycosis patients from India.

Coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM) was reported predominantly from India during the second wave of COVID-19  and has a high mortality rate. The present study aims to understand the fungal community composition of the nasopharyngeal region of CAM-infected individuals and compare it with severe COVID-19 patients and healthy controls. The fungal community composition was decoded by analyzing the sequence homology of the internal transcribed spacer-2-(ITS-2) region of metagenomic DNA extracted from the upper respiratory samples. The alpha-diversity indices were found to be significantly altered in CAM patients (p < 0.05). Interestingly, a higher abundance of Candida africana, Candida haemuloni, Starmerella floris, and Starmerella lactiscondensi was observed exclusively in CAM patients. The interindividual changes in mycobiome composition were well supported by beta-diversity analysis (p < 0.05). The current study provides insights into the dysbiosis of the nasal mycobiome during CAM infection. In conclusion, our study shows that severe COVID-19 and CAM are associated with alteration in mycobiome as compared to healthy controls. However, the sequential alteration in the fungal flora which ultimately leads to the development of CAM needs to be addressed by future studies.

Rhizopus arrhizus infection in mice causes brain histopathological alterations and exacerbates neuronal apoptosis.

Rhizopus arrhizus is a fungus that can cause central nervous system infections in animals, resulting in high morbidity and mortality, but the mechanism of injury is rarely reported. In this study, we investigated the mechanism of Rhizopus arrhizus damage to the central nervous system of mice by observing the clinical neurological symptoms and resolving the pathological changes in the ultrastructure of brain tissues, combined with the alteration of apoptosis-related genes and immunohistochemistry (IHC). The results showed that all the mice in the treated group died, the brain pyknosis of neurons, there were black mycelium aggregates around the blood vessels, and apoptotic vesicles were produced. The RT-qPCR results showed that, compared with the control group, the relative transcriptome levels of Caspase 8 and BcL-2 genes were significantly increased (P < 0.05), the relative transcriptome level of Caspase 9 gene was highly significant (P < 0.01), the relative transcriptome level of Caspase 3 and Bax gene was significantly decreased (P < 0.05), and the ratio of Bcl-2/Bax was significantly increased (P < 0.05) in the brains of the treated group. TUNEL staining showed that the rate of neuronal apoptosis in the treated group of mice was extremely significantly higher than that in the control group (P < 0.01). This study shows that Rhizopus arrhizus strain XMLO1 causes brain damage by triggering neuronal apoptosis. This study provided a theoretical basis for revealing the mechanism of Rhizopus arrhizus infection.

The mutual value of histopathology and ITS sequencing in the diagnosis of mucormycosis.

AIMS: Mucormycosis is a fast-progressing disease with a high mortality rate. The most important factor determining survival of patients is early and accurate diagnosis. Although histopathology often recognises invasive mould infections at first, histomorphology alone is insufficient in providing an accurate diagnosis. Unbiased molecular methods to detect and identify fungi are promising, yet their role in complementing routine histopathological workflows has not been studied sufficiently. METHODS AND RESULTS: We performed a retrospective single-centre study examining the clinical value of complementing histopathology with internal transcribed spacer (ITS) sequencing of fungal DNA in the routine diagnosis of mucormycosis. At our academic centre, we identified 14 consecutive mucormycosis cases diagnosed by histopathology and subsequent ITS sequencing. Using histomorphological examination, fungal hyphae could be detected in all cases; however, morphological features were unreliable regarding specifying the taxa. Subsequent ITS sequencing identified a remarkable phylogenetic diversity among Mucorales: the most common species was Rhizopus microsporus (six of 14; 42.9%), followed by Lichtheimia corymbifera (three of 14, 21.4%) and single detections of Rhizopus oryzae, Actinomucor elegans, Mucor circinelloides, Rhizomucor pusillus and Rhizomucor miehei (one of 14; 7.1%, respectively). In one case, we additionally detected Pneumocystis jirovecii in the same lung tissue specimen, suggesting a clinically relevant co-infection. Fungal culture was performed in 10 cases but yielded positive results in only two of 10 (20%), revealing its limited value in the diagnosis of mucormycosis. CONCLUSIONS: Our study demonstrates that a combination of histopathology and ITS sequencing is a practically feasible approach that outperforms fungal culture in detecting Mucorales in tissue-associated infections. Therefore, pathologists might adapt diagnostic workflows accordingly when mucormycosis is suspected.

COVID-19 associated mucormycosis surge: A review on multi-pathway mechanisms.

Mucormycosis is a fungal infection caused by moulds from the Mucorales order. Concerns have been mounting due to the alarming increase in severe morbidity and mortality associated with mucormycosis during the COVID-19 pandemic. This condition, known as COVID-19-associated mucormycosis (CAM), has been linked to various environmental, host-related, and medical factors on a global scale. We have categorized the most significant potential risk factors for developing mucormycosis in individuals with a previous history of coronavirus infection into 10 major categories. These categories include acute hyperglycemia, the impact of cytokine release, immune response deficiencies in COVID-19 patients, microvasculopathy and dysfunction of endothelial cells, imbalances in iron metabolism, metabolic acidosis, organ damage resulting from COVID-19, underlying health conditions (such as diabetes), environmental factors, and medical treatments that can be iatrogenic in nature (such as inappropriate glucocorticoid use). Many of these factors can lead to potentially life-threatening infections that can complicate the treatment of COVID-19. Physicians should be vigilant about these factors because early detection of mucormycosis is crucial for effective management of this condition.

Performance of Mucorales spp. qPCR in bronchoalveolar lavage fluid for the diagnosis of pulmonary mucormycosis.

To estimate the diagnostic performance of Mucorales polymerase chain reaction (PCR) in Bronchoalveolar lavage fluid (BALF) in routine practice. This was a single-center retrospective study including all consecutive patients >18 years who underwent Mucorales PCR assay in BALF between January 2021 and May 2022. Index testing was prospectively performed using the MycoGENIE Aspergillus spp.-Mucorales spp. PCR. The reference was the diagnosis of pulmonary mucormycosis by the Adjudication Committee. Mucorales PCR in BALF was performed for 938 patients and was positive for 21 of 938 (2.2%). Eleven pulmonary mucormycosis (including one disseminated) were diagnosed. Among them, one (9.1%) was classified as proven mucormycosis, three (27.3%) as probable, and seven (63.6%) as possible according to the EORTC/MSGERC 2019 criteria. The main host factor was hematological malignancy (10 of 11, 90.9%). Mucorales PCR was positive in serum for eight patients (72.7%). Three patients had positive PCR in BALF, but negative in serum. The mean cycle threshold value was significantly lower in mucormycosis than false-positive cases. Sensitivity was 72.7% (95% confidence interval [CI], 43.4-90.3%), and specificity was 98.6% (95% CI, 97.6-99.2%). The positive and negative predictive values were 38.1% (95% CI, 20.8-59.1%) and 99.7% (95% CI, 99.1-99.9%), respectively. Mucorales PCR in BALF showed good diagnostic performance for mucormycosis, particularly in combination with serum PCR. A positive result should be interpreted with caution, given the possibility of carriage in the airway. However, its high negative predictive value and specificity suggest the utility of Mucorales PCR in BALF in the diagnosis of pulmonary mucormycosis.

Use of the Mucorales qPCR on blood to screen high-risk hematology patients is associated with better survival.

Our objective was to determine whether the twice-weekly screening of high-risk hematology patients by Mucorales qPCR on serum affects the prognosis of mucormycosis. Results from all serum Mucorales qPCR tests performed on patients from the hematology unit from January 2017 to December 2022 were analyzed. Patients with positive results were classified as having proven, probable or 'PCR-only' mucormycosis. One-month mortality for the local cohort was compared with that of a national cohort of cases of mucormycosis collected by the French surveillance network for invasive fungal disease ('Réseau de surveillances des infections fongiques invasives en France' (RESSIF)) from 2012 to 2018. From 2017 to 2022, 7825 serum Mucorales qPCR tests were performed for patients from the hematology unit; 107 patients with at least one positive Mucorales qPCR (164 positive samples) were identified. Sixty patients (70 positive samples, median Cq = 40) had no radiological criteria for mucormycosis and were considered not to have invasive fungal disease (70/7825, 0.9% false positives). It was not possible to classify disease status for six patients (12 positive samples, median Cq = 38). Forty-one patients (82 positive samples, median Cq = 35) had a final diagnosis of mucormycosis. In comparison with the RESSIF cohort, the local cohort was independently associated with a 48% lower one-month all-cause mortality rate (age-, sex-, and primary disease-adjusted hazard ratio = 0.52; 95% confidence interval: 0.29-0.94; P 0.03). Proactive screening for invasive mold diseases in high-risk hematology patients, including twice-weekly Mucorales qPCR on serum, was associated with mucormycosis higher survival.

Rapid detection of Mucorales in human blood and urine samples by functionalized Heusler magnetic nanoparticle assisted customized loop-mediated isothermal amplification.

Mucormycosis is a rare disease with scarce diagnostic methods for early intervention. Available strategies employing direct microscopy using calcofluor white-KOH, culture, radiologic, and histopathologic testing often are time-intensive and demand intricate protocols. Nucleic Acid Amplification Test holds promise due to its high sensitivity combined with rapid detection. Loop-mediated isothermal amplification (LAMP) based detection offers an ultrasensitive technique that does not require complicated thermocyclers like in polymerase chain reaction, offering a straightforward means for improving diagnoses as a near-point-of-care test. The study introduces a novel magnetic nanoparticle-based LAMP assay for carryover contaminant capture to reduce false positives. Solving the main drawback of LAMP-based diagnosis techniques. The assay targets the cotH gene, which is invariably specific to Mucorales. The assay was tested with various species of Mucorales, and the limit of detections for Rhizopus microsporus, Lichtheimia corymbifera, Rhizopus arrhizus, Rhizopus homothallicus, and Cunninghamella bertholletiae were 1 fg, 1 fg, 0.1 pg, 0.1 pg, and 0.01 ng, respectively. This was followed by a clinical blindfolded study using whole blood and urine samples from 30 patients diagnosed with Mucormycosis. The assay has a high degree of repeatability and had an overall sensitivity of > 83%. Early Mucormycosis detection is crucial, as current lab tests from blood and urine lack sensitivity and take days for confirmation despite rapid progression and severe complications. Our developed technique enables the confirmation of Mucormycosis infection in < 45 min, focusing specifically on the RT-LAMP process. Consequently, this research offers a viable technique for quickly identifying Mucormycosis from isolated DNA of blood and urine samples instead of invasive tissue samples.

Mucormycosis is a challenging disease to diagnose early. This study introduces a sensitive and rapid diagnostic approach using Loop-mediated isothermal amplification technology. Testing blood and urine samples from 30 patients revealed promising sensitivity and repeatability, indicating its potential for non-invasive diagnosis.

Predicting intracranial involvement: Unveiling perineural spread in COVID-19-associated mucormycosis, a novel phenomenon.

This study aimed to investigate the risk factors associated with intracranial involvement in COVID-19-associated mucormycosis (CAM) and to develop a nomogram model for predicting the risk of intracranial involvement, with a specific focus on perineural spread. An ambispective analysis was conducted on 275 CAM patients who received comprehensive treatment. Univariable and multivariable logistic regression analyses were performed to identify independent risk factors, and a nomogram was created based on the results of the multivariable analysis. The performance of the nomogram was evaluated using a receiver operating characteristic (ROC) curve, and the discriminatory capacity was assessed using the area under the curve (AUC). The model's calibration was assessed through a calibration curve and the Hosmer Lemeshow test. In the results, the multivariable logistic regression analysis revealed that age (OR: 1.23, 95% CI 1.06-3.79), HbA1c (OR: 7.168, 95% CI 1.724-25.788), perineural spread (OR: 6.3, 95% CI 1.281-19.874), and the disease stage were independent risk factors for intracranial involvement in CAM. The developed nomogram demonstrated good discriminative capacity with an AUC of 0.821 (95% CI 0.713-0.909) as indicated by the ROC curve. The calibration curve showed that the nomogram was well-calibrated, and the Hosmer Lemeshow test yielded a P-value of 0.992, indicating a good fit for the model. In conclusion, this study found that CAM particularly exhibits perineural spread, which is a predictive factor for intracranial involvement. A nomogram model incorporating age, HbA1c, disease stage, and perineural spread was successfully developed for predicting intracranial involvement in CAM patients in both in-patient and out-patient settings.

Discovery of perineural spread in COVID-19-associated mucormycosis reveals a new predictive model for intracranial complications which is crucial for early intervention.

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.

The Nairobi Declaration 2023: A commitment to address deadly yet neglected fungal diseases in Africa.

On May 30th and 31st, 2023, delegates representing various African subregions, together with global representatives from the International Society of Human and Animal Mycology (ISHAM), the European Confederation of Medical Mycology (ECMM), the United States Centre for Disease Control and Prevention (CDC), and Global Action for Fungal Infections (GAFFI), convened in Nairobi, Kenya under the aegis of the Pan African Mycology Working Group, a working group of ISHAM. The meeting objectives were, amongst others, to deliberate on a continental response to the World Health Organisation Fungal Priority Pathogen List and facilitate interaction between global and regional leaders. Country delegates and international speakers addressed Africa's fungal disease burden; capacity for diagnosis and management; ongoing surveillance; knowledge gaps and trends in invasive fungal diseases such as Candida auris, mucormycosis, aspergillosis, and Acquired Immune Deficiency Syndrome (AIDS)-related mycoses; and current laboratory practice. During the technical sessions, expert panels deliberated on establishing and financing of national/regional surveillance networks for mycoses; establishing and sustaining African-led collaborations; expanding on existing laboratory and point-of-care diagnostic capacity as well as planning a mycology reference laboratory service and network in Africa. The meeting also highlighted successful African-led collaborations, capacity building, and clinical trial initiatives. The meeting conclusions informed the resolutions of the Nairobi Declaration calling for improved awareness; strong collaborations between clinical and laboratory teams across Africa; improved fungal disease surveillance within the continent; access to antifungals and diagnostics; and leveraging qualified human resources for mycology present within and outside Africa to facilitate trainings, collaborations, and exchanges.

This review presents the current state of the art in medical mycology in Africa discussed at the first scientific meeting of the Pan African Mycology Working Group, an affiliate of the International Society for Human and Animal Mycology (ISHAM) held in Nairobi, Kenya on May 30th and 31st, 2023.

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.

Rhinocerebral mucormycosis in immunocompetent patients: a case report and review of literature.

INTRODUCTION: Mucormycosis of the head and neck region is a rare but aggressive fungal infection that usually involves immunocompromised patients. More infrequently, this infection can also occur in people with no otherwise known underlying immunological deficit. This rarity usually causes a delay in diagnosis and may severely decrease the chance of survival in these patients. In this study, we present an extreme case of mucormycosis in an immunocompetent patient. By conducting a thorough review of the literature, we aim to increase our knowledge on this matter. Our goal is to improve diagnosis and start treatment at an earlier stage. CASE PRESENTATION AND METHODS: Our patient was a 31-year-old man who presented with bilateral face numbness, neck pain, headache, and a necrotic palatal lesion 45 days after a dental root canal procedure. There was extensive involvement of facial and skull base bony and soft tissues. Through two debridement sessions and intravenous antifungal treatment, the patient was discharged with near-complete disease resolution. We identified 48 cases in the literature that matched our study criteria. We searched the current literature for proven cases of mucormycosis in the head and neck region who didn't have any underlying disease. We extracted their data and added the data of our patient. Then, we re-analyzed them using descriptive analysis, chi-square, and binary logistic regression to better understand the different factors for survival and disease burden in these patients. RESULTS: 49 patients were analyzed in this study. The mean age was 46.93 ± 15.75 (min 16 and max78 years old). The most prevalent subsite to be involved was the sino-nasal mucosa, followed by the surrounding soft tissues and the orbit. While both orbit and intracranial tissue involvement differed significantly between surviving and deceased patients, only intracranial tissue involvement could be used to predict survival. The overall survival rate was 91.8%. CONCLUSION: Although very rare, mucormycosis can occur in immunocompetent patients. Physicians should consider mucormycosis when faced with refractory conditions and unusual symptoms such as exposed bones, facial numbness, headaches, and intractable pain. Complementary imaging (CT scan with or without MRI) and histopathological examination are critical for timely diagnosis or exclusion of this potentially fatal yet treatable disease.

Progressive multifocal leukoencephalopathy in a patient with B-cell chronic lymphocytic leukemia after COVID-19 vaccination, complicated with COVID-19 and mucormycosis: a case report.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rare and fatal opportunistic viral demyelinating infectious disease of the central nervous system (CNS). There are various clinical presenting symptoms for the disease. CASE PRESENTATION: This paper presents a clinical case of PML in a patient with B-Chronic lymphocytic leukemia (B-CLL), previously treated with Chlorambucil, later complicated later with COVID-19 and mucormycosis. CONCLUSION: PML can develop in the setting of cellular immune dysfunction. Late diagnosis of this disease based on nonspecific symptoms is common, therefore when we face a neurological complication in a CLL or immunocompromised patient, we should consider PML infection. A remarkable feature of this case is the possible triggering effect of COVID-19 vaccination for emergence of PML as the disease can be asymptomatic or sub-clinical before diagnosis.

Mucormycosis mimicking portal hypertensive haemorrhage as a complication of alcoholic liver cirrhosis: a case report.

Mucor is a rare cause of gastrointestinal ulcers. This case describes a case of mucormycosis that occurred in a patient with liver cirrhosis who was hospitalized to accept a splenectomy for traumatic splenic rupture. During the perioperative period, the patient developed upper gastrointestinal bleeding(UGIB), which was diagnosed as mucormycosis-related gastric ulcer according to gastroscopy. Patients with liver cirrhosis often get UGIB for Portal hypertension, but they also can develop UGIB for multiple other reasons, including infectious ulcers for immunosuppression. The case emphasizes the importance of excluding fungal-induced ulcer haemorrhage before diagnosing Portal hypertensive-induced variceal haemorrhage in patients with liver cirrhosis.