Investigating the Hepcidin Gene Polymorphisms in COVID-19-Associated Mucormycosis Susceptibility: A Clinical-Laboratory Study.

Background: Following the coronavirus disease 2019 outbreak (COVID-19), it became a worrisome health burden worldwide. COVID-19-associated mucormycosis emergence, characterized by dysregulated inflammation and iron metabolism, exacerbated the prognosis of affected patients. Given the significance of hepcidin in regulating inflammation and iron metabolism, this study investigated the significance of hepcidin single nucleotide polymorphisms (SNP) in COVID-19-associated mucormycosis development, along with the association between the clinical and laboratory factors and COVID-19-associated mucormycosis. Methods: From September 2021 to November 2021, COVID-19 patients with and without mucormycosis were enrolled in this cross-sectional study. Their medical records and laboratory results were investigated. SNP genotyping was performed using Sanger sequencing. Hardy-Weinberg Equilibrium, Pearson's Chi square, and student t test were used for analyzing the data using SPSS software version 25. P<0.05 was regarded as statistically significant. Results: Here, 110 COVID-19 patients with and without mucormycosis were investigated. Elevated levels of urea, aspartate aminotransferase, lactate dehydrogenase, and increased ratio of polymorphonuclear neutrophil to lymphocytes were associated with decreased risk of COVID-19-associated mucormycosis in patients (all P<0.05). Moreover, diabetes mellitus increased the risk of mucormycosis (P=0.028). In contrast to patients without mucormycosis, patients with mucormycosis did not display 442 GA and SNP335 GT genotypes. Unlike patients without mucormycosis, none of the patients with mucormycosis had SNP442 GA and SNP335 GT genotypes. Regarding SNP 443 C>T, and the combination of SNPs 582 A>G and 443 C>T, CC genotype and AA+CC genotypes were associated with increased lactate dehydrogenase levels in COVID-19 patients, respectively. Conclusion: Regarding SNP 443 C>T, the CC genotype was associated with increased lactate dehydrogenase levels in COVID-19 patients. In terms of SNP 582 A>G and SNP 443 C>T, COVID-19 patients with AA+CC genotypes had higher levels of LDH. None of the patients with mucormycosis had SNP442 GA and SNP335 GT genotypes.

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.

A Case of Invasive Pulmonary Mycosis (Rhizopus microspores) secondary to Hematological Disease.

BACKGROUND: Pulmonary mucormycosis is most common in patients with hematologic malignancies and transplant recipients. This article describes a case of mucormycosis in the lungs secondary to a hematologic disorder with suspected lung cancer. METHODS: Rhizopus (Rhizopus microspores) was detected by blood NGS and bronchoalveolar lavage fluid NGS, and pulmonary mucormycosis was confirmed. RESULTS: Secondary to hematologic disease, pulmonary pneumonia, mycosis, and symptoms improved after comprehensive treatment. CONCLUSIONS: Clinical data and radiologic knowledge are combined to diagnose invasive pulmonary mycoses; early empirical medicine is very important.

Aspergillosis coinfection in patients with proven mucormycosis.

Although research on aspergillosis and mucormycosis confection is important to optimize antifungal therapy, data on this issue is scarce. Thus, we systematically investigated aspergillosis coinfection in patients with proven mucormycosis. Medical records of adult patients with proven mucormycosis whose formalin-fixed paraffin-embedded (FFPE) tissue sections were available, in a tertiary hospital from August 2007 to July 2023 were retrospectively reviewed to assess coinfection with aspergillosis. We noted cultures of fungi from sterile and non-sterile sites and performed polymerase chain reaction (PCR) assays on FFPE tissues to detect Aspergillus- and Mucorales-specific DNA. Sixty-seven patients with proven mucormycosis, including 12 (18%) with a positive culture of the mucormycosis agent from sterile site cultures, were enrolled. Fungal cultures from sterile and non-sterile sites revealed Aspergillus spp. growth in nine (13%) of the 67 patients, including two sterile and seven non-sterile cultures. The fungal PCR analysis from the FFPE sections was positive for Aspergillus-specific PCR in five (7%) and positive for both Aspergillus- and Mucorales-specific PCR results in eight (12%). Overall, 21 (31%) of the 67 patients with proven mucormycosis had microbiologic and/or molecular evidence of aspergillosis coinfection. Positive blood or bronchoalveolar lavage fluid galactomannan results were more common in the coinfection group (67% [14/21]) than in the mucormycosis group (37% [17/46], P = .024). No significant difference in mortality between the two groups was observed. Approximately one-third of patients with proven mucormycosis exhibited molecular and/or microbiologic evidence of aspergillosis coinfection. Further research is needed to identify patients with aspergillosis and mucormycosis coinfections, for optimal antifungal therapy.

The study aims to investigate the coinfection between mucormycosis and aspergillosis. Key findings reveal that approximately 31% of patients demonstrated evidence of coinfection, which emphasizes the importance of considering both pathogens in diagnosis and treatment decisions.

Cutaneous mucormycosis infection owing to Rhizomucor variabilis presenting as recurrent lower limb ulceration and cellulitis in a diabetic patient.

Primary cutaneous mucormycosis is caused by environmental fungi and may complicate leg ulcers or traumatic wounds even in immunocompetent individuals. This case report highlights recurrent lower limb ulcers and cellulitis in a patient with type two diabetes mellitus, which was unresponsive to conventional antibiotic treatment. Histopathology revealed the diagnosis of cutaneous mucormycosis, and fungal cultures identified Rhizopus variabilis as the causative organism. Initial courses of oral azole antifungals yielded only partial response and he eventually required more aggressive treatment with i.v. amphotericin B and oral posaconazole. Good treatment outcomes for this condition require a high index of clinical suspicion, early histopathological and microbiological diagnosis, targeted systemic antifungal therapy, and surgical debridement if necessary.

Rhinocerebral mucormycosis and Trichosporon asahii fungemia in a pediatric patient with acute lymphoblastic leukemia: a rare coinfection.

Mucormycosis is a rare life-threatening opportunistic infection, with rhinocerebral mucormycosis (ROCM) being the most common presentation. Trichosporon asahii is an emerging pathogen that often causes fatal infections in patients with underlying hematologic malignancies due to its high drug resistance. We report a rare case of concomitant rhinocerebral mucormycosis and T. asahii fungemia secondary to Pseudomonas aeruginosa sepsis in a patient with neutropenia and acute lymphoblastic leukemia. A boy aged one year and two months was diagnosed with B-cell acute lymphoblastic leukemia on January 10 and underwent three courses of regular chemotherapy. He experienced neutropenia for 154 days and was hospitalized for vomiting, diarrhea and fever for 3 days. The day after hospitalization, Pseudomonas aeruginosa was isolated by blood culture and ceftazidime/avibactam was administered. Extracorporeal Membrane Oxygenation (ECMO) was used to provide continuous extracorporeal respiration and circulation for the patient. On day 8, the patient developed T. asahii fungemia. On day 10, he presented with necrotizing skin caused by Rhizopus delemar. He was treated with liposomal amphotericin B for Rhizopus delemar and voriconazole for T. asahii infection. Unfortunately, his health deteriorated and he died on day 11 due to the rapid progression of the infection and multiple organ failure. The management and treatment of such a complex infection requires a multidisciplinary approach and close monitoring of the patient's condition. Therefore, it is imperative to continue to research and report rare cases such as this to further understand the complexities of mucormycosis and trichosporidiosis coinfection and improve patient outcomes.

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.

Rapidly Progressing Rhino-orbito-cerebral Mucormycosis with Concomitant Pulmonary Mucormycosis in a Post-COVID-19 Diabetic Subject.

SUMMARY: Invasive fungal sinusitis is a highly lethal infection in an immunocompromised population that can spread rapidly to involve the adjacent structures by direct invasion or through vascular invasion. Involvement of cerebral parenchyma by vascular invasion is a devastating complication in these patients which may lead to vasculitis, thrombus formation, cerebritis, or abscess formation. Here, we present a case of a young male with uncontrolled diabetes mellitus who initially presented with COVID-19 lung disease and later developed sinonasal mucormycosis complicated with left orbital cellulitis and pulmonary mucormycosis.

Long-term Outcome of Coronavirus Disease-associated Mucormycosis: 1-year Follow-up Study from India.

IMPORTANCE: Invasive fungal infections have recently become a public health problem, particularly in India following the second wave of coronavirus disease 2019 (COVID-19). India harbors the world's largest population of patients suffering from diabetes. What prompted the sudden spike of mucormycosis infections in the COVID pandemic needs investigation. OBJECTIVE: To determine if COVID-19 infection prompted the spike in invasive fungal infections in diabetic population. To determine the long-term outcome of COVID-associated mucormycosis. To determine if COVID-19 infection causes diabetes mellitus transiently. DESIGN: The study was a prospective cohort study comprising patients suffering from mucormycosis. The study was planned from 20 May 2021, until 30 November 2022, to investigate the long-term follow-up (1 year) of mucormycosis patients. SETTING: The study setting was a referral hospital. PARTICIPANTS: All the consecutive patients admitted to this hospital for treatment of mucormycosis were included in the study who consented to it. Intervention(s) (for clinical trials) or exposure(s) (for observational studies): All patients suffering with mucormycosis underwent treatment at this hospital with surgery and injectable systemic antifungal drugs alongside diabetes management. MAIN OUTCOME(S) AND MEASURE(S): Primary outcome measurement was in the form of survival with cure of mucormycosis. Hypothesis being tested was formulated during data collection. RESULTS: The data of 98 participants was collected, but analysis was done after excluding the case of cutaneous mucormycosis (infant patient). Mean age for patients was 55.5 years, varying from 28 to 88 years. In our study, 63.3% of patients with mucormycosis were males and 37.8% were females, of which 55.7% (34) and 58.3% (21) were known diabetics, respectively. Previous history of diabetes mellitus was identified as an underlying comorbid condition in 56.7% of patients, while the rest were diagnosed with new-onset diabetes mellitus. Sugar levels ranged (on admission) from 112 to 494 mg/dL (median 212 mg/dL) for known diabetics and from 132 to 356 mg/dL (median 204 mg/dL) for newly diagnosed diabetics. Other comorbidities included hypertension (19.5%), ischemic heart disease (8.2%), chronic renal illness (3.09%), and one case (1.03%) of postoperative renal cell carcinoma (disease-free). The majority of cases (91.8%) were not vaccinated for COVID-19, while only two patients reported a history of vaccination with two doses, and six others had received only a single dose. At the 1-year follow-up, 57.7% of cases were disease-free, 30.9% had expired, and 11.3% were lost to follow-up. The mean glycated hemoglobin (HbA1c) at the time of admission was found to be statistically significant when compared between known diabetics and newly diagnosed ones [confidence interval (CI)-95%, p ≤ 0.01]. A total of seven patients from the newly diagnosed diabetic group no longer required medicines for diabetes at the end of 1 year (CI-95%, p ≤ 0.01). CONCLUSIONS AND RELEVANCE: Diabetes mellitus, particularly with poor glycemic control, was the single most important factor associated with and predictor of outcome. Contrary to the popular hypothesis, industrial oxygen and oxygen masks were not the reasons for the mucormycosis pandemic. Additionally, immunization against COVID provided protection not only from severe COVID but also from COVID-associated mucormycosis. It is recommended that patients with mucormycosis be followed for longer periods as a few patients could be suffering from transient diabetes, particularly against the backdrop of a pandemic.

[Fatal case of rhinocerebral mucormycosis on the background of type II diabetes mellitus]. / Letal'nyi sluchai rinotserebral'nogo mukormikoza na fone sakharnogo diabeta 2-go tipa.

Mucormycosis is a disease caused by fungi of the Mucorales family, widespread in the environment, with pronounced angiotropism and the ability to angioinvasion, leading to thrombosis with surrounding necrosis. The main triggers for the development of mucormycosis are: immunodeficiency states, use of glucocorticosteroid drugs, decompensation of diabetes mellitus, concomitant diseases, age > 65 years. We present a clinical case of rhinocerebral mucormycosis in a 79-year-old patient against the background of uncontrolled type 2 diabetes mellitus with ketoacidosis, a condition after previous glucocorticosteroid therapy for COVID-19 (according to the severity of the disease). After suffering a new coronavirus infection caused by the SARS-CoV-2 virus, she was admitted to the hospital with complaints characteristic of mucormycosis. On the 5th day of hospital stay, the patient's condition worsened significantly, despite the correction of the therapy, and on the 12th day the patient died. According to the results of the autopsy, it was established that the rhinocerebral mucormycosis was complicated by thrombosis of the anterior and posterior left cerebral arteries with subsequent infarctions in the frontal lobe and parieto-occipital region of the brain left hemisphere, cerebral edema, which was the immediate cause of death.

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.

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.

Oral mucormycosis associated with COVID-19 and diabetes mellitus: Case report and literature review / Mucormicosis oral asociada a COVID-19 y diabetes mellitus: descripción de un caso.

Mucormycosis is an invasive opportunistic fungal infection with high mortality, mainly detected in people with COVID-19, especially those with underlying diseases such as diabetes mellitus. Mucormycosis prevalence is 0.005 to 1.7 cases per million inhabitants, and it has been increasing in countries like India and Pakistan. This mycosis can affect different organs, and clinical manifestations reflect the transmission mechanism. Frequent forms are rhino-orbital-cerebral and pulmonary. This disease should be suspected in patients with necrotic injuries on mucous membranes or skin. We present a case of a patient with diabetes mellitus and diagnosed with oral mucormycosis associated with COVID-19.

La mucormicosis es una infección fúngica oportunista e invasiva, con una elevada tasa de mortalidad. Se ha detectado principalmente en pacientes con COVID-19, especialmente en personas con enfermedades concomitantes como la diabetes mellitus. La prevalencia de las mucormicosis es de 0,005 a 1,7 casos por millón de habitantes y ha ido en aumento en países como India y Pakistán; puede afectar diferentes órganos y su forma clínica refleja el mecanismo de transmisión. Entre las formas frecuentes están la rino-orbital-cerebral y la pulmonar, por ello, debe sospecharse mucormicosis en los pacientes con lesiones necróticas en mucosas o piel. Se presenta el caso de un paciente con antecedentes de diabetes mellitus que fue diagnosticado con mucormicosis oral asociada a la COVID-19.