Mucormycosis-induced brain abscess treatment without dura opening- a report of three cases (preprint)

purpose Brain abscess following sinonasal mucormycosis is a rare but life-threatening condition that usually occurs during the patient's treatment. Therefore, it is important to pay close attention to its identification and treatment and since our knowledge is mostly based on case reports, a well-documented way of treatment for such cases is yet to be found. Methods A retrospective case series study was conducted at a tertiary hospital. Initially, all patients with brain abscesses following sino-nasal mucormycosis were included, and then patients whose brain abscesses were treated without opening the dura during surgery were selected for the study. The patients received radical debridement of necrotic tissues as well as the infected bones adjacent to the brain abscess cavity. But the dura was not incised. Then they were treated medically for their underlying disease and also with Amphotericine-B. Their brain abscess was monitored 3 weeks post-operatively. Results Three patients with an average age of 41 years were included in the study. All patients had a history of diabetes and had previously been treated for COVID-19 before developing symptoms of sino-nasal infection. The average size of the abscesses was less than 2 cm. Two patients had abscesses in the temporal lobe and one in the frontal lobe. Conclusion Treating brain abscesses adjacent to the skull base by removing infected tissues and bones surrounding the brain abscess without opening the dura can be a viable treatment option for mucormycosis-induced brain abscesses of less than 2 cm. Ethics approval statement: IR.TUMS.AMIRALAM.REC.1402.036

FUNGAL OSTEOMYELITIS OF FRONTAL BONE FOLLOWING COVID ASSOCIATED MUCORMYCOSIS (preprint)

Introduction: - The second wave of COVID 19 lead to resurgence of opportunistic infections due to injudicious use of steroids. Sinonasal Mucormycosis was declared as an epidemic during the pandemic. The mucormycosis was managed effectively by surgical debridement along with systemic amphotericin B. Now, following the initial treatment of mucormycosis there is a resurgence, in the form of fungal osteomyelitis of the frontal bone. Methods – the prospective study included the cases from ten patients with fungal osteomyelitis of frontal bone due to mucormycosis, all the patients underwent surgical debridement of sequestrum and involucrum with systemic antifungals. Results - The average duration of the recurrence was 22 days following the initial treatment Range (10 days to 33 days). Extracranial bossing following outer frontal cortex erosion in 30% of cases, bicortical erosion in 30%, bifrontal involvement (20%), dural involvement (30%), brain parenchymal involvement and prefrontal cortex (20%) case. All cases underwent debridement of entire sequestrous bone and involucrum till normal bone was identified. The mean duration of admission was 4 weeks (3 to 6 weeks). All treated patients are currently alive without disease, confirmed by CECT. Conclusion - The successful treatment of fungal osteomyelitis due to mucormycosis requires four pronged approach (1) early detection (2) multidisciplinary management of comorbidities (3) surgical debridement of necrotic bone and (4) adequate systemic antifungal therapy. Long term outcomes of fungal osteomyelitis of frontal bone are yet to be established

An unpremeditated complication of COVID-19 and mucormycosis: a case report, brief review, and warning for tunnel vision (preprint)

Over the course of the Coronavirus disease 2019 (COVID-19) pandemic, numerous complications have been documented. In this report, we have detailed an unexpected complication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that occurred in a 73-year-old female patient who was simultaneously afflicted with mucormycosis and another unanticipated problem. Due to the lack of recovery of the patient after receiving mucormycosis treatment and continued fever, cough and hemoptysis, bronchoscopy was performed for her. During bronchoscopy, we encountered a foreign body that was the cause of the patient's fever, cough, and hemoptysis. Rigid bronchoscopy was performed and a foreign body (2.7 x 1.2 cm) was removed from the left main bronchus. Although research has showed fewer cases of pediatric Foreign Body Aspiration (FBA) during lockdown periods, there is not enough evidence about FBA risk in elderly patients with comorbidities. Finally, in the treatment of cases of COVID-19 infections co-infected with opportunistic fungal and maybe even bacterial infections, we should not look at the patient through a tunnel vision and consider all possible scenarios for the patient.

A case of COVID-19-associated rhino-orbito-cerebral mucormycosis caused by Apophysomyces variabilis with a review of the literature.

A fatal case of COVID-19-associated mucormycosis (CAM) affected a 40-year-old woman who was initially admitted to our hospital due to a SARS-CoV-2 infection. Her clinical condition worsened, and she finally died because of respiratory failure, hemodynamic instability, and mucormycosis with invasion into the orbit and probably the brain. According to DNA sequence analysis of the fungus isolated from the patient, Apophysomyces variabilis was involved. This is the first published case of CAM and the third case of mucormycosis due to this mold.

[Clinical case of mucormycosis in patient COVID-19. Case report].

The COVID-19 epidemic is being revealed from a new angle every month. In particular, with the appearance of the delta strain, mucormycosis began to manifest in some patients, which had previously been extremely rare. Mucormycosis is a rare, aggressive infection caused by filamentous fungi of the Mucorales family and associated with high morbidity and mortality rates. The main risk factors for the mucormycosis in patients with COVID-19 are diabetes mellitus and diabetic ketoacidosis, uncontrolled hyperglycemia and massive use of glucocorticoids, vascular damage, thrombosis, lymphopenia, which often occur against the background of COVID-19 and make a person vulnerable to secondary or opportunistic fungal infection. We present a clinical case of mucormycosis in a 21-year-old female patient with COVID-19-associated severe pneumonia and concomitant type I diabetes mellitus. The patient was hospitalized and received standard therapy during inpatient treatment, including glucocorticosteroids in accordance with the severity of the course of COVID-19. On the 12th day from the hospitalization, the patient's condition deteriorated significantly, and the visible changes in the skin and soft tissues of the face, characteristic of mucormycosis appeared. Despite the drug therapy correction, the patient died because of the acute respiratory failure in combination with septic fungal damage of the brain stem.

Clinical and Neuroimaging Characteristics of Ischemic Stroke in Rhino-Orbito-Cerebral Mucormycosis Associated with COVID-19.

PURPOSE: The aim of this study was to compare clinical, neuroimaging, and laboratory features of rhino-orbito-cerebral mucormycosis (ROCM) in COVID-19 patients with and without ischemic stroke complications. METHODS: This observational study was conducted between August and December 2021 and 48 patients who had confirmed ROCM due to COVID-19, according to neuroimaging and histopathology/mycology evidence were included. Brain, orbit and paranasal sinus imaging was performed in all included patients. Data pertaining to clinical, neuroimaging, and laboratory characteristics and risk factors were collected and compared between patients with and without ischemic stroke complications. RESULTS: Of the patients 17 were diagnosed with ischemic stroke. Watershed infarction was the most common pattern (N = 13, 76.4%). Prevalence of conventional risk factors of stroke showed no significant differences between groups (patients with stroke vs. without stroke). Cavernous sinus (p = 0.001, odds ratio, OR = 12.8, 95% confidence interval, CI: 2.3-72) and ICA (p < 0.001, OR = 16.31, 95%CI: 2.91-91.14) involvement was more common in patients with stroke. Internal carotid artery (ICA) size (on the affected side) in patients with ischemic stroke was significantly smaller than in patients without stroke (median = 2.4 mm, interquartile range, IQR: 1.3-4 vs. 3.8 mm, IQR: 3.2-4.3, p = 0.004). Superior ophthalmic vein (SOV) size (on the affected side) in patients with stroke was significantly larger than patients without stroke (2.2 mm, IQR: 1.5-2.5 vs. 1.45 mm IQR: 1.1-1.8, p = 0.019). Involvement of the ethmoid and frontal sinuses were higher in patients with stroke (p = 0.007, OR = 1.85, 95% CI: 1.37-2.49 and p = 0.011, OR = 5, 95% CI: 1.4-18.2, respectively). Patients with stroke had higher D­dimer levels, WBC counts, neutrophil/lymphocyte ratios, and BUN/Cr ratio (all p < 0.05). CONCLUSION: Stroke-related ROCM was not associated with conventional ischemic stroke risk factors. Neuroimaging investigations including qualitative and quantitative parameters of cavernous sinus, ICA and SOV are useful to better understand the mechanism of stroke-related ROCM in COVID-19 patients.

[COVID-19 associated sino-orbital mucormycosis]. / COVID-19-assotsiirovannyi sinoorbital'nyi mukormikoz.

OBJECTIVE: To analyze the dynamics of symptoms in patients with COVID-19 associated sino-orbital mucormycosis. MATERIAL AND METHODS: We describe a series of 13 patients with COVID-19 associated sino-orbital mucormycosis aged 43 to 80 years diagnosed from August to October 2021. All of the patients had a severe disease and required noninvasive ventilation or intubation and administration of dexamethasone. 12 out of 13 patients (92.3%) suffered from diabetes mellitus. Symptoms of fungal infections of the nose and paranasal sinuses appeared in the interval from 7 to 25 days of hospital stay, most often in the second week (from 8 to 12 days). According to clinical and CT features the patients were divided into three groups, combining similar phenotypes of the disease. Group 1 - 1 patient with sinonasal mucormycosis, destruction of the alveolar ridge and the hard palate. Group 2 - 12 patients with sino-orbital mucormycosis. We noted, that in cases of bilateral sinus lesions orbital complications were unilateral in all patients, on the side of more severe lesion. Group 2 was divided into 2 subgroups: subgroup 2a included 2 patients with the superior orbital fissure syndrome: ptosis, proptosis, ophthalmoplegia, periorbital pain, pain or hypoesthesia of half face; subgroup 2b included 10 patients with the orbital apex syndrome, who, in addition to the above symptoms, had loss of vision and conjunctival chemosis. Group 3 - rhino-sino-cerebral mucormycosis. 2 patients from subgroup 2b were transferred to this group due to the intracranial spread of the process and focal neurological symptoms. CONCLUSION: Clinical forms of mucormycosis reflect successive stages of invasive spread of fungi.

Case Reports on Black Fungus of the Gastrointestinal Tract: A New Complication in COVID-19 Patients.

Gastrointestinal mucormycosis is a rare disease with a significant mortality rate, even when promptly diagnosed and treated. An unusual complication was observed in India during the second wave of coronavirus disease 2019 (COVID-19). Two incidences of gastric mucormycosis were found. A 53-year-old male patient with a history of COVID-19 one month earlier came into the intensive care unit. After admission, the patient developed hematemesis, which was initially treated with blood transfusions and digital subtraction angiography embolization. Esophagogastroduodenoscopy (EGD) revealed a large ulcer with a clot in the stomach. During an exploratory laparotomy, the proximal stomach was necrotic. Histopathological examination confirmed mucormycosis. The patient was started on antifungals, but despite rigorous therapy, the patient died on the tenth postoperative day. Another patient, an 82-year-old male with a history of COVID-19, arrived with hematemesis two weeks earlier and was treated conservatively. EGD revealed a large white-based ulcer with abundant slough along the larger curvature of the body. Mucormycosis was verified by biopsy. He was treated with amphotericin B and isavuconazole. He was discharged after two weeks in a stable condition. Despite quick detection and aggressive treatment, the prognosis is poor. In the second case, prompt diagnosis and treatment saved the patient's life.

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

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

A case of COVID-19-associated mucormycosis due to Lichtheimia ramosa.

BACKGROUND: Mucormycosis is a life-threatening invasive fungal infection in immunocompromised and COVID-19 patients. CASE REPORT: Here, we report a fatal rhino-orbito-cerebral mucormycosis caused by Lichtheimia ramosa, in a 79-year-old diabetic female. She was initially admitted to the hospital for COVID-19 infection and received broad-spectrum antibiotics and corticosteroids. After 1 month, she was admitted again because of persistent headaches and decreased right eye movement when the computed tomography scan showed mucosal thickening and opacification of paranasal sinuses. Microbiological investigations, including culture and direct microscopy, and histopathological findings confirmed the diagnosis of proven mucormycosis. The isolated causal agent was identified as Lichtheimia ramosa by sequencing the entire ITS region of nuclear ribosomal DNA. Despite surgical debridement and administration of liposomal amphotericin B 5 mg/kg/day, the patient's level of consciousness suddenly deteriorated; she was intubated and mechanically ventilated in the ICU and died on the same day. CONCLUSION: To our knowledge, this is the first worldwide case of COVID-19-associated rhino-orbito-cerebral mucormycosis due to Lichtheimia ramosa.

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

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

Magnet-Retained closed bulb hollow obturator and orbital prosthesis for patient with maxillectomy and orbital exenteration following COVID-Associated mucormycosis.

The rehabilitation of facial deformities is a challenging endeavour that necessitates customising the procedure for each patient. Significant physical and psychological impacts might arise as a result of the deformity in the orofacial region. Post-COVID rhino-orbital mucormycosis has led to rise in extraoral and intraoral defects since 2020. To avoid further surgery, an economical maxillofacial prosthesis is an excellent choice as it is aesthetic, durable, long-lasting and retentive. This case report describes the prosthetic rehabilitation of the patient with post-COVID mucormycosis maxillectomy and orbital exenteration using a magnet-retained closed bulb hollow acrylic obturator and room-temperature vulcanising silicone orbital prosthesis. To enhance retention, a spectacle and medical-grade adhesive were also used.

Central Retinal Artery Occlusion in Rhino-Orbital-Cerebral Mucormycosis: An Inflammatory-Prothrombotic State.

PURPOSE: The aim was to evaluate patient profiles of rhino-orbital-cerebral mucormycosis (ROCM) cases with central retinal artery occlusion (CRAO) postcoronavirus disease 2019. DESIGN: A nonrandomized retrospective case-control study. METHODS: The ROCM cases presenting with CRAO were compared with a control ROCM group without CRAO at a tertiary care center. Demography, systemic status, clinical features, histopathology, imaging, and blood profile were assessed for any specific risk factors. RESULTS: A total of 12 patients were seen in the CRAO group and 16 in the non-CRAO group. The male-to-female ratio was 3:1 with a mean age of 49.5 years. In the CRAO group, 75% had diabetes mellitus with mean hemoglobin A1c of 9.03%, and 66.7% had received steroid treatment. All cases were histopathologically confirmed positive for mucor. There was a significant difference in mean D-dimer and serum ferritin between the 2 groups, with higher level in the CRAO group. All patients with CRAO had light perception-negative vision, with total ophthalmoplegia and proptosis seen in 66.7% of cases. Four patients had orbital apex involvement, 5 had cavernous sinus involvement, and 8 had intracranial involvement in the CRAO group. CONCLUSIONS: Inflammatory markers D-dimer and serum ferritin were significantly associated with CRAO, suggestive of hyperinflammatory and hypercoagulable state. A high index of suspicion should be maintained in cases with elevated markers and prophylactic anticoagulants can be started to prevent CRAO in a subset of patients.

Ramification of COVID-19 pandemic : Occurrence and impact of fungal infections in a tertiary care hospital (preprint)

Coronavirus disease 2019 (COVID-19) pandemic has been prevailing for more than a year associated with increased number of opportunistic invasive fungal infections in patients who have been critically ill or immunocompromised. In this retrospective study, details of various clinical specimens received from suspected patients of fungal infections were processed according to standard protocol were studied. The fungal infections were present in 64% (51/79) COVID-19 positive patients and 43% (163/381) COVID-19 negative patients) during the year 2021 during the second wave of COVID-19. Among COVID-19 infected patients, the fungal infection mostly observed was Candidiasis (63%) followed by Aspergillosis (15% ) and Mucormycosis (6%). The maximum samples positive in COVID-19 patients were urine samples followed by Serum (for Aspergillus Galactomannan). Among the urine and respiratory samples (BAL, Tracheal aspirate, Sputum) in COVID-19 positive patients, maximum positivity of Candida species was seen. Mucormycosis in COVID-19 positive patients was isolated in Nasal samples followed by tissue sample with Rhizopus arrhizus and Rhizopus homothallicus. There has been an increase in fungal co-infections during the COVID-19 pandemic which is a matter of great concern. Early diagnosis is essential for effective management of these patients.

Fungal infection profile in critically ill COVID-19 patients: a prospective study at a large teaching hospital in a middle-income country.

BACKGROUND: Critically ill COVID-19 patients are highly susceptible to opportunistic fungal infection due to many factors, including virus-induced immune dysregulation, host-related comorbidities, overuse and misuse of antibiotics or corticosteroids, immune modulator drugs, and the emergencies caused by the pandemic. This study aimed to assess the incidence, identify the potential risk factors, and examine the impact of fungal coinfection on the outcomes of COVID-19 patients admitted to the intensive care unit (ICU). METHODS: A prospective cohort study including 253 critically ill COVID-19 patients aged 18 years or older admitted to the isolation ICU of Zagazig University Hospitals over a 4-month period from May 2021 to August 2021 was conducted. The detection of a fungal infection was carried out. RESULTS: Eighty-three (83) patients (32.8%) were diagnosed with a fungal coinfection. Candida was the most frequently isolated fungus in 61 (24.1%) of 253 critically ill COVID-19 patients, followed by molds, which included Aspergillus 11 (4.3%) and mucormycosis in five patients (1.97%), and six patients (2.4%) diagnosed with other rare fungi. Poor diabetic control, prolonged or high-dose steroids, and multiple comorbidities were all possible risk factors for fungal coinfection [OR (95% CI) = 10.21 (3.43-30.39), 14.1 (5.67-35.10), 14.57 (5.83-33.78), and 4.57 (1.83-14.88), respectively]. CONCLUSION: Fungal coinfection is a common complication of critically ill COVID-19 patients admitted to the ICU. Candidiasis, aspergillosis, and mucormycosis are the most common COVID-19-associated fungal infections and have a great impact on mortality rates.

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

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