Mucormycosis during COVID-19 era: A retrospective assessment.

In a retrospective view, this review examines the impact of mucormycosis on health workers and researchers during the COVID era. The diagnostic and treatment challenges arising from unestablished underlying pathology and limited case studies add strain to healthcare systems. Mucormycosis, caused by environmental molds, poses a significant threat to COVID-19 patients, particularly those with comorbidities and compromised immune systems. Due to a variety of infectious Mucorales causes and regionally related risk factors, the disease's incidence is rising globally. Data on mucormycosis remains scarce in many countries, highlighting the urgent need for more extensive research on its epidemiology and prevalence. This review explores the associations between COVID-19 disease and mucormycosis pathology, shedding light on potential future diagnostic techniques based on the fungal agent's biochemical components. Medications used in ICUs and for life support in ventilated patients have been reported, revealing the challenge of managing this dual onslaught. To develop more effective treatment strategies, it is crucial to identify novel pharmacological targets through "pragmatic" multicenter trials and registries. In the absence of positive mycology culture data, early clinical detection, prompt treatment, and tissue biopsy are essential to confirm the specific morphologic features of the fungal agent. This review delves into the history, pathogens, and pathogenesis of mucormycosis, its opportunistic nature in COVID or immunocompromised individuals, and the latest advancements in therapeutics. Additionally, it offers a forward-looking perspective on potential pharmacological targets for future drug development.

Mucormycosis, the Black Fungus in the Post-COVID-19 Pandemic: A Case Report with Review of Literature.

Mucormycosis, a concerning and often fatal fungal infection, has shown a significant rise in cases following the COVID-19 pandemic in India, particularly affecting patients with uncontrolled comorbidities such as diabetes mellitus and other immunocompromised individuals. Our case series examines five instances of mucormycosis, supported by appropriate radiographic and histopathological evidence correlating with clinical observations. Our review indicated that patients were experiencing ailments or undergoing treatments that compromised their immune systems. We analyzed additional epidemiological data, including common infection sites, gender predispositions, and mortality rates. Treatments were tailored based on symptom severity, encompassing both surgical and medical approaches. The primary reason for the rise in cases was linked to elevated glycaemic levels and weakened immunity among post-COVID-19 patients. The report provides a detailed explanation of the factors contributing to this correlation. Our findings underscore the critical importance of timely surgical intervention and advocate for further investigation into treatment efficacy and symptom monitoring specific to mucormycosis in post-COVID-19 patients in India.

Diagnosis of mucormycosis from nasal swabs using commercial PCR platforms; a feasible alternative?

Rhino-orbital-cerebral mucormycosis (ROCM) is linked to uncontrolled diabetes, diabetic ketoacidosis, iron overload, corticosteroid therapy, and neutropenia. This study evaluated a commercial real-time PCR system's effectiveness in detecting Mucorales from nasal swabs in 50 high-risk patients. Nasal swab PCR showed 30% positivity, compared to 8% with KOH microscopy. Despite its improved sensitivity, nasal swab PCR has limitations, highlighting the importance of established sampling methods in mucormycosis diagnosis. Participants were predominantly male (64%), with diabetes (78%) and amphotericin B use (96%). Prior COVID-19 was 42%, with 30% positive for Mucorales by PCR, compared to 8% with KOH microscopy.

A Retrospective Study of Imaging of Invasive Rhino-Orbital-Cerebral Mucormycosis in the COVID-19 Pandemic in a Tertiary Care Center.

Aim The study aims to analyze the imaging findings of invasive rhino-orbital-cerebral mucormycosis (ROCM) in patients who had COVID-19. Materials and methods This retrospective descriptive study was done on confirmed (culture and histopathology) patients who had a COVID-19 infection. The data was collected from the record section from May 2021 to June 2021. Imaging data were analyzed, and findings were tabulated according to statistical methods. Results Radiological evaluation, including CT and MRI, was done in 48 cases. The ethmoid sinus was the most common sinus involved in 60.41% of cases, followed by the maxillary sinus (52.09%). Unilateral pansinusitis was observed in 21 cases (43.75%). Among periantral extensions, retroantral fat involvement was the most common finding, seen in 24 cases (50%). Lamina papyracea and the walls of the maxillary sinus were involved in eight cases (16.67%). A total of 38 cases (79.17%) exhibited involvement of the extraconal compartment, while 32 cases (66.67%) showed involvement of the intraconal compartment. In intracranial involvement, infarct was noted in 13 cases (27%), and cavernous sinus involvement in nine cases (18.75%). Conclusions ROCM is a life-threatening fungal infection in immunocompromised patients, especially diabetics. Imaging of ROCM plays a pivotal role in early diagnosis, the extent of disease, surgical planning, prognosis, and the response to treatment. Radiologists must know the imaging features and patterns of extension of ROCM.

Case report: Disseminated mucormycosis misdiagnosed as malignancy developed from allergic bronchopulmonary mycosis caused by Rhizopus microsporus following SARS-CoV-2 infection in a woman.

Mucormycosis has become more prevalent during the COVID-19 pandemic and is associated with a high mortality rate. However, concurrent host allergic reactions, invasive pulmonary mucormycosis, and disseminated mucormycosis are rarely reported. Herein, we describe a case of disseminated mucormycosis initially misdiagnosed as a malignancy that developed from allergic bronchopulmonary mycosis caused by Rhizopus microsporus in a woman with post-SARS-CoV-2 infection. The previously healthy patient presented with a sizeable mass in the right middle lobe and multiple lesions across the lungs, brain, spleen, kidneys, pancreas, and subcutaneous tissue 6 months after SARS-CoV-2 infection, mimicking an extensive metastatic malignancy. Eosinophilia, elevated total plasma immunoglobulin E, and significant eosinophilic lung tissue infiltration were observed. Rhizopus microsporus was isolated from subcutaneous tissue, and hyphae were detected in the lung tissue. Sequential amphotericin B liposomes followed by isavuconazole antifungal therapy combined with systemic corticosteroids improved symptoms, significantly reduced the sizes of pulmonary lesions, and reduced eosinophil count. However, it failed to halt the overall progression of the disease, and the patient died. The absence of asthma-like symptoms and delayed recognition of invasive fungal infection signs contributed to poorer outcomes, highlighting the need for a thorough post-COVID-19 follow-up.

Increased serum ferritin is associated with severity of orbital disease in COVID-19-associated rhino-orbito-cerebral mucormycosis: A quantitative analysis.

CONTEXT: Effect of serum ferritin on severity of coronavirus disease 2019 (COVID-19)-associated rhino-orbito-cerebral mucormycosis. PURPOSE: To study the association between increased serum ferritin and severity of orbital disease in COVID-19-associated rhino-orbito-cerebral mucormycosis. SETTINGS AND DESIGN: A cross-sectional study. METHODS: Hundred (n) out of 155 treatment-naive patients of COVID-19 infection presenting with the signs and symptoms of rhino-orbito-cerebral mucormycosis were enrolled in study. Based on the classification proposed by Honavar, the study patients were classified into four stages: Stage 1: involvement of the nasal mucosa (n = 11), Stage 2: involvement of paranasal sinuses (n = 14), Stage 3: involvement of the orbit (n = 37), Stage 4: involvement of the central nervous system (n = 38). Stage 3 was further divided into four substages: 3a: nasolacrimal duct, medial orbit, vision unaffected (n = 4); 3b: diffuse orbital involvement (>1 quadrant or >2 structures), vision unaffected (n = 15); 3c: central retinal artery occlusion or ophthalmic artery occlusion, superior ophthalmic vein thrombosis, involvement of superior orbital fissure, inferior orbital fissure, orbital apex, diminution or loss of vision (n = 13); 3d: bilateral orbital involvement (n = 5). Fasting blood sugar (FBS), postprandial blood sugar (PPBS), and inflammatory markers (serum ferritin, interleukin-6, C-reactive protein, and D-dimer) were assessed. Serum level of ferritin was analyzed by using chemiluminescence immunoassay method. RESULTS: Mean FBS (mg/dl) was 165.03 ± 70.43 for stage 1, 185.67 ± 64.82 for stage 2, 159.05 ± 68.60 for stage 3, and 158.20 ± 62.05 for stage 4. Mean PPBS (mg/dl) was 238.70 ± 141.29 for stage 1, 252 ± 103.69 for stage 2, 257.09 ± 103.48 for stage 3, and 229.53 ± 76.81 for stage 4. Mean serum ferritin (µg/l) was 302.67 ± 266.95 in stage 1, 444.19 ± 116.36 in stage 2, 504.85 ± 205.99 in stage 3, and 825.95 ± 777.30 in stage 4. A statistically significant increase in serum ferritin levels with severity of disease (P = 0.005) was noted. Similar trend was observed in substages of stage 3. Pearson correlation analysis showed a positive correlation between serum ferritin and severity of disease (P = 0.0007). CONCLUSION: Increased serum ferritin was significantly independently associated with severity of orbital disease in COVID-19-associated rhino-orbito-cerebral mucormycosis.

Secondary bacterial infections in post-COVID-19 mucormycosis cases: a retrospective study at Imam Khomeini Hospital Complex, March 2020-April 2021.

Background and Objectives: To explore the prevalence and characteristics of secondary bacterial infections among patients suffering from mucormycosis following COVID-19 infection. Materials and Methods: We conducted a cross-sectional, retrospective analysis from March 2020 to April 2022 at Imam Khomeini Hospital Complex in Tehran. The study included patients with histopathologically confirmed mucormycosis and documented secondary bacterial infections. We extracted and analyzed data from hospital records using SPSS software, version 26. Results: The study comprised 27 patients, with a predominance of females (70.4%) and an average age of 56 years. The majority of these patients (63%) had pre-existing diabetes mellitus. The severity of their COVID-19 infections varied. Treatment regimens included immunosuppressive drugs and antibiotics. Rhinocerebral mucormycosis was the most common form observed. The predominant secondary infections involved the urinary tract, respiratory system, bloodstream (bacteremia), and soft tissues, with resistant strains of Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae being the most frequently identified microorganisms. Notably, cases of bacteremia and pneumonia exhibited a higher mortality rate. Ultimately, 55.6% of patients were discharged, while 44.4% succumbed to their infections. Conclusion: Patients recovering from COVID-19 with mucormycosis are significantly susceptible to secondary bacterial infections, particularly those with diabetes mellitus or those undergoing immunosuppressive therapy. Such infections compound the morbidity and mortality risks in this vulnerable patient cohort.

Resurgence of orbital mucormycosis during COVID-19 pandemic: Study from a tertiary care center in Eastern India.

PURPOSE: A sudden surge of Mucormycosis cases during the second wave of Covid 19 was observed in certain parts of India. The reasons for this upsurge remain unknown. However its impact on the overall healthcare system was quite overwhelming. In this context this study was decided to estimate and assess the spectrum of orbital involvement in patients with Mucormycosis, to find its association with coexisting disease entities if any, and at the same time evaluate the therapeutic response to established treatment regimens. MATERIALS AND METHODS: This descriptive longitudinal study was conducted over a period of six months. Patients presenting with symptoms of Mucormycosis were jointly evaluated by a multi speciality team. After confirmation of diagnosis, patients were treated with intravenous Amphotericin B, surgical debridement of affected sinuses and orbital exenteration when indicated. They were followed up for three months after discharge. RESULTS: Forty-three patients were enrolled in this study. Thirty-seven (86.04%) were COVID positive. All of them had history of steroid exposure during COVID treatment. Ninety five percent of study participants had diabetes mellitus. Twenty-seven (62.79%) patients had orbital involvement. Most common clinical presentation was peri-orbital or facial pain and edema. Besides medical treatment, thirty-nine patients (90.69%) required sinus debridement and nine patients (20.9%) required orbital exenteration. Thirteen patients (30.23%) expired during the follow up period. With treatment disease regressed in twenty patients (46.51%). CONCLUSION: Diabetes and use of steroids to prevent anticipated cytokine storm may be the inciting factors for Orbital Mucormycosis in COVID patients. Early diagnosis, treatment and control of risk factors are keys for recovery and survival..

Rehabilitation of the Surgical Defect Secondary to Mucormycosis With a Definitive Obturator: A Case Report.

Neglect initially starts as an infection, evolving into a disease. During the COVID-19 pandemic, lifestyle changes and disturbed food intake have weakened immune systems, making individuals more susceptible to secondary infections. Mucormycosis poses a significant threat, especially during the COVID-19 pandemic when immune systems may be compromised. The impact of the disease extends beyond physical health, affecting psychological and social well-being due to the challenges, such as difficulties in mastication, speech, and swallowing post-surgery. The mention of maxillectomy highlights the severe nature of some cases, necessitating surgical intervention to remove the affected tissue. Anatomical and functional losses following surgical excision of the maxilla and surrounding tissues need to be recovered as soon as possible. After surgery, prostheses can and should be used to restore speech, mastication, and deglutition - three essential physiological activities. Thus, a patient's treatment approach should include prosthetic planning before surgical intervention and rehabilitation after the surgery. If they are carefully handled at the moment of surgery, the overall continuity created by maxilla resection includes at least the oral, nasal, and maxillary sinus cavities, which may prove to be a useful future location for prosthesis retention. As a result, the prosthodontist's role becomes crucial in assisting the surgeon in taking all necessary precautions that are beneficial to the patient.

Retrospective study of patient characteristics and treatment for mucormycosis in post COVID-19 population in a tertiary care hospital.

OBJECTIVES: Along with the COVID-19 pandemic, another illness wreaking havoc in India is mucormycosis, also known as black fungus. Mucormycosis was previously known as zygomycotic infection, which is a consequential type of infection caused by several mildews known as Mucoromycetes. It is an invasive type of disease which occurs more commonly in individuals with low and weakened immunity. The main objective of this study was to identify the mucormycosis cases post COVID-19 and to determine the risk factors and treatment for positive cases. METHODS: Thirty-three patients (61% men, 39% women; mean age 55 years) with mucormycosis were identified in the Department of Oral and Maxillofacial Surgery. RESULTS: People who received COVID-19 vaccines had a lower rate of infection with the fungus than non-vaccinated people. In steroid users the risk was very high compared with those not taking steroids. CONCLUSION: The majority of non vaccinated patients with preexisting co-morbidity conditions like diabetes, chronic illnesses and irregular use of steroids during COVID-19, might have greater risks of getting mucormycosis rather than normal COVID-19 positive cases.

An interesting report of COVID-19 associated mucormycosis (CAM) cases by two different species of Mucorales.

During surge of COVID-19-associated mucormycosis (CAM), we identified five cases of CAM where two different species of Mucorales were isolated. All had history of diabetes mellitus and presented with clinical features suggesting rhino-orbital mucormycosis. The patients grew different species from their nasal scraping/biopsy samples, Rhizopus arrhizus, R. homothallicus (n = 2); R. homothallicus, Lictheimia corymbifera (n = 1); R. arrhizus, Mucor spp (n = 1); and L. corymbifera, Apophysomyces variabilis (n = 1). All patients underwent surgical and medical (liposomal amphotericin B) treatment. All, except one growing A. variabilis and L. corymbifera survived. Mixed infection by more than one Mucorales in CAM is unique and warrants epidemiological investigation.

[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.

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.

Risk Factors Associated with Mortality in Patients with Mucormycosis Post Severe Acute Respiratory Syndrome Coronavirus-2 (Sars-Cov-2) Infection.

To study the potential risk factors associated with mortality in patients with mucormycosis. A retrospective study of 490 patients with diagnosis of sinonasal mucormycosis was done. They were divided in two groups-Group A included 87 patients that expired during the study period and Group B included 403 control patients. All the demographic, clinical and outcome parameters were collected from the patient's record files and noted in a structured case proforma and were analysed. During the mean hospital stay of 22 ± 6 days, 17.7% patients expired during the treatment course. Multiple risk factors like uncontrolled diabetes, dyselectrolytemia, underlying renal disease and extensive nature of the disease involving orbit, intracranium and with pulmonary dissemination, all were associated with high mortality in Mucormycosis. Early recognition and appropriate management of the secondary factors can grossly reduce the risk of mortality in patients with mucormycosis.

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.

Risk factors and clinical presentation of rhino-orbital mucormycosis: Lesson learnt during Covid pandemic.

Aim: To analyze the potential predisposing factors and clinical presentation of mucormycosis in patients with COVID-19. Material and Methods: Medical records of 141 patients with COVID-19-associated mucormycosis (CAM) treated at a tertiary care center in Bihar were reviewed. The predisposing factors, clinical features, and imaging findings of mucormycosis were analyzed. Results: The median age was 48 years (IQR, 43-60). A total of 58 patients developed concurrent CAM and 83 post-CAM. The median interval between COVID-19 and onset of CAM symptoms was 15 days (IQR, 9-16). A total of 80 patients received at-home treatment for COVID-19, and 73 had mild-to-moderate disease. While 61 patients received in-hospital treatment, 57 had severe disease. At presentation, 131 patients had hyperglycemia: 64 type 2 diabetes mellitus (DM) and 67 new-onset DM. The history of glucocorticoid use for COVID-19 was present in 125 patients; 47% were administered at home without monitoring plasma glucose. The common presenting features were toothache, periocular or facial pain, and edema. Rhino-orbital mucormycosis was the most common. Imaging revealed rhinosinusitis in all patients, including pansinusitis (68%), pterygopalatine fossa involvement (21%), cavernous sinus thrombosis (38%), brain abscess (8%), and infarct (4%). All patients received intravenous liposomal amphotericin B, and surgical debridement was performed in 113. Conclusion: COVID-19 patients with hyperglycemia are at risk of developing CAM, irrespective of the severity. Timely recognition of symptoms and prompt initiation of therapy by primary healthcare physicians are imperative for enhancing outcomes. Additionally, glucocorticoid overuse should be avoided, and close monitoring for hyperglycemia development is warranted.

Magnetic Resonance Imaging in COVID-19 Associated Rhino-Sinusal Mucormycosis.

Rhino-sinusal mucormycosis is an acute invasive fungal infection rarely encountered in the clinical setting, occurring in severe immunosuppressed patients. However, in patients suffering from COVID-19 disease a dramatic increase in the incidence of mucormycosis has been recorded. The aim of the study is to discuss the MRI findings of patients with COVID-19 associated mucormycosis. This is a retrospective review of 10 hospitalized and operated patients in three Otolaryngologic Departments between the 1st of February 2021 and the 30th of October 2021. All patients presented nasal mucormycosis, histologically verified along with documented SARS-CoV-2 positive RT-PCR test. The sinus involvement, extra sinus spread and peri-sinus invasion were documented in all patients. The correlation between MRI and intra-operative findings was also assessed. The black turbinate sign and peri-antral soft tissue infiltration are early MRI signs characteristic of mucormycosis. Moreoever, MRI has a significantly high positive predictive value for intra-operative findings in COVID-19 associated mucormycosis.