Risk factors for pulmonary mucormycosis in subjects with diabetes mellitus-A case-control study.

BACKGROUND: Factors associated with pulmonary mucormycosis (PM) among subjects with diabetes mellitus (DM) remain unclear. Following the coronavirus disease (COVID-19)-associated mucormycosis outbreak in India, specific environmental exposures (especially cattle dung exposure) were proposed as possible aetiology. We hypothesized that environmental factors are associated with PM. We compared subjects with DM with (cases) and without PM (controls). METHODS: In this case-control study, for each PM case, we included five unmatched diabetic controls (hospital [n = 2], community [n = 3]) without PM. We collected information on demography, COVID-19 infection, glycated haemoglobin% (HbA1c), the type of house (pucca vs. kutcha) where the participants reside, and other environmental factors. The primary exposure tested was cattle dung exposure (CDE; using cattle dung cakes as fuel or cattle handling). We performed a multivariate logistic regression to explore factors associated with PM and report the association as an adjusted odds ratio (OR) with 95% confidence intervals (CI). RESULTS: We enrolled 39 PM cases and 199 controls (hospital [n = 80], community [n = 119]). CDE (OR 0.68, 95% CI [0.14-3.31]; p = 0.63) was not associated with increased PM in DM. We found male sex (OR 4.07, 95% CI [1.16-14.31]), higher HbA1c (OR 1.51, 95% CI [1.18-16.32]), COVID-19 (OR 28.25, 95% CI [7.02-113.6]) and residence at kutcha house (OR 4.84, 95% CI [1.33-17.52]) associated with PM. CONCLUSION: Cattle dung exposure was not associated with PM in subjects with DM. Instead, male sex, poor glycaemic control, COVID-19 and the type of housing were associated with pulmonary mucormycosis.

Epidemiology of COVID-19-Associated Mucormycosis.

Purpose of the Review: To describe the epidemiology and risk factors for Coronavirus disease-19 (COVID-19)-associated mucormycosis (CAM) based on current published literature. Recent Findings: COVID-19 is associated with an increased risk of secondary infections. Mucormycosis is an uncommon invasive fungal infection that typically affects people with immunocompromising conditions and uncontrolled diabetes. Treatment of mucormycosis is challenging and is associated with high mortality even with standard care. During the second wave of the COVID 19 pandemic, an abnormally high number of CAM cases were seen particularly in India. Several case series have attempted to describe the risk factors for CAM. Summary: A common risk profile identified for CAM includes uncontrolled diabetes and treatment with steroids. COVID-19-induced immune dysregulation as well as some unique pandemic specific risk factors may have played a role.

Evaluation of prognostic factors in management of associated COVID-19 oro-facial mucormycosis

After the declaration of coronavirus as a pandemic in 2019, a strong relationship has been shown between the sudden upsurge of mucormycosis occurrence in patients with history of COVID-19. This relation can be explained by the effect of coronavirus on the patient's immune system, the infection worsens the effect of the underlying predisposing factors such as diabetes mellitus and drugs therapies that were used in the treatment of COVID-19, especially corticosteroids. Mucormycosis presented mainly in patients who had comorbid conditions like diabetes, steroid therapy, or chemotherapy. This study showed the association between the increase in the prevalence of mucormycosis in patients with COVID-19 and proved that dia-betes was the main risk factor for this fungal infection. The study confirmed that many factors determined the prognosis in the management of mucormycosis, first of them is the early diagnosis which depends on a high index of clinical suspicion, accurate procedures for diagnosis confirmation such as biopsy, fungal culture media, radiological examination by computed tomography scan or magnetic resonance imaging, early initiation of antifungal therapy either Amphotericin-B or Liposomal Amphotericin-B as soon as the diagnosis is confirmed and aggressive surgical debridement of all infected tissues (Figure 1).

COVID-related mucormycosis mimicking dental infection.

A recent increase in the prevalence of mucormycosis of the head and neck in patients who have recovered from COVID-19 following hospitalization has been reported. A Majority of the cases have been reported from India. Conditions such as diabetes mellitus, use of corticosteroids for other autoimmune conditions, organ transplant, immunosuppression, immunodeficiency, and malignancies especially hematologic ones, are all known risk factors for mucormycosis. Recently, hospitalization for COVID-19 has been added to the list of risk factors for opportunistic mucormycosis infection. This is likely attributable to the high doses and prolonged use of corticosteroids in the treatment of hospitalized COVID-19 patients. Case Description: Two patients with post-COVID-19 associated rhinocerebral mucormycosis presented with profound unexplained dental disease including tooth mobility and dental abscess mimicking periodontal disease. The patients were previously hospitalized for COVID-19 and received prolonged treatment with high doses of corticosteroids. The patients responded well to the surgical debridement with or without antifungal therapy. Conclusion: Oral healthcare providers including oral and maxillofacial surgeons, dentists, dental hygienists, and other dental practitioners can play a vital role in the recognition and early diagnosis of rhinocerebral mucormycosis given the large number of patients with severe COVID-19 infection who have recovered following hospitalization and/or received long-term high doses of immunosuppressive treatment.

Mucormycosis following COVID-19: clinical case and literature review.

Mucormycosis is one of the most aggressive invasive mycoses. The mortality rate of patients with mucormycosis, depending on clinical form and background disease, varies from 30% to 100%. This article provides the first description of mucormycosis in Russia after infection caused by SARS-CoV-2, as well as a review of literature reports on mucormycosis in patients with COVID-19 (as of September 2021).Copyright © 2021, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

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.

Post-COVID mucormycosis in presentation of periodontal abscess.

COVID-19 pandemic has traumatized deep inside in minds and lives of human beings. Those who have survived are at risk of many post-COVID complications; mucormycosis being one of the most common as well as morbid infections. Mucormycosis is also known as black fungus, it is a life-threatening opportunistic fungal infection. Inoculation occurs by inhalation of spores in nose, paranasal air sinuses and in lungs. Mucormycosis is often associated in patients with compromised immunity and it presents with characteristic black necrotic eschar and necrosis. Disease affecting the facial region possess a challenge because it often disseminates with sino-orbital and cranial involvement at the time of diagnosis. Dental practice occasionally encounters unusual and subtle symptoms with non-pathognomonic clinical signs of several fatal diseases which may pretend like a common oral disease. Hence, the key knowledge to oral and primary care physicians and its precise application is necessary for the early diagnosis of such fatal infections to prevent untoward consequences in this COVID era. This article presents a case of mucormycosis with chief complaint of pain and swelling in right front tooth region, which mimicked as periodontal abscess in a patient, leading to delay in the diagnosis possess greater challenges during the treatment.

Epidemiology of Mucormycosis in Greece; Results from a Nationwide Prospective Survey and Published Case Reports.

Mucormycosis has emerged as a group of severe infections mainly in immunocompromised patients. We analysed the epidemiology of mucormycosis in Greece in a multicentre, nationwide prospective survey of patients of all ages, during 2005-2022. A total of 108 cases were recorded. The annual incidence declined after 2009 and appeared stable thereafter, at 0.54 cases/million population. The most common forms were rhinocerebral (51.8%), cutaneous (32.4%), and pulmonary (11.1%). Main underlying conditions were haematologic malignancy/neutropenia (29.9%), haematopoietic stem cell transplantation (4.7%), diabetes mellitus (DM) (15.9%), other immunodeficiencies (23.4%), while 22.4% of cases involved immunocompetent individuals with cutaneous/soft-tissue infections after motor vehicle accident, surgical/iatrogenic trauma, burns, and injuries associated with natural disasters. Additionally, DM or steroid-induced DM was reported as a comorbidity in 21.5% of cases with various main conditions. Rhizopus (mostly R. arrhizus) predominated (67.1%), followed by Lichtheimia (8.5%) and Mucor (6.1%). Antifungal treatment consisted mainly of liposomal amphotericin B (86.3%), median dose 7 mg/kg/day, range 3-10 mg/kg/day, with or without posaconazole. Crude mortality was 62.8% during 2005-2008 but decreased significantly after 2009, at 34.9% (p = 0.02), with four times fewer haematological cases, fewer iatrogenic infections, and fewer cases with advanced rhinocerebral form. The increased DM prevalence should alert clinicians for timely diagnosis of mucormycosis in this patient population.

New onset unusual Wegener's granulomatosis associated with COVID-19: a case report

Background: Granulomatosis with polyangiitis (GPA) or Wegener's granulomatosis is an autoimmune disorder with a wide spectrum of manifestations that mostly primarily presents with respiratory symptoms such as cough, dyspnea, and hemoptysis and leads to a high mortality rate if left untreated. It is a relatively uncommon condition, characterized by necrotizing granulomatous vasculitis of small-and medium-sized vessels. Recent studies have shown that hyperactivation of immune cells in patients with the coronavirus disease 2019 (COVID-19) leads to elevated levels of various autoantibodies and inflammatory cytokines including interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). There are the same factors that involve in the pathogenesis of autoimmune diseases such as GPA.Case presentation: While there have been several reported cases of COVID-19 occurring in patients receiving immunosuppressant treatment for GPA, here we report a case of a 72-year-old woman with a history of coronavirus disease 2019 (COVID-19) who suddenly suffered unilateral vision and hearing loss and peripheral facial palsy on the same side. Chest computed tomography (CT) demonstrated a subpleural consolidation in the inferior lobe of the left lung. Based on the radiology report, chest CT evidence was due to a history of COVID-19 pneumonia. CT scans of the paranasal sinus showed pansinusitis and necrosis of the nasal septum. According to the available evidence, mucormycosis was clinically suspected, and the patient underwent endoscopic sinus surgery. Eventually, the histopathological analysis revealed a diagnosis of Wegener's granulomatosis.Conclusions: Since GPA and its complications can be prevented only through strong clinical suspicion and early diagnosis, our presentation of this case aims to increase awareness of autoimmune diseases in COVID-19 patients even after recovery.

Mucormycosis - A Rare, yet Lethal Infection: A Review

Mucormycosis is an angio invasive infection caused by Mucorales fungi, which is mostly observed in diabetic and immunocompromised patients. The infection can be classified into cutaneous, rhino-orbito cerebral, gastrointestinal, disseminated and other rare pulmonary types. The overall mortality rate due to this infection has increased, even with aggressive treatment. Moreover, there has been a major mucormycosis outbreak in India following the deadly second wave of COVID-19 cases in the country. The epidemiology of mucormycosis is evolving due to advances in therapeutics and early diagnostics tools. The aim of this review is to provide an overview of the epidemiology, pathogenesis and types of mucormycosis along with an update on the recent advanced diagnostics tools and therapeutics to combat the rare, yet lethal infection.

Mucormycosis of the Mandible Following Sars-Cov- 2 Infection - a Case Report with a Brief Review of Literature

Mucormycosis is a rare fungal infection of the craniofacial region and lungs. An upsurge in the cases of mucormycosis was observed in the patients who had a history of SARS-CoV-2 infection.Infact in India, mucormycosis was declared an epidemic during the second wave of the COVID-19 pandemic. Rhino-orbital and cerebral regions were most commonly involved and very few cases of mandibular involvement have been reported in Post-COVID-19 Mucormycosis in India. Herewith, we report a case of isolated mandibular mucormycosis in a COVID-19 patient. A 47-year-old patient who recently recovered from COVID-19 presented with typical symptoms of osteomyelitis which was confirmed by radiological findings. An incisional biopsy followed by histopathologic examination confirmed mucormycosis of the mandible. Mucormycosis is an aggressive fungal infection thatrequires prompt diagnosis and treatment. Judicious management of osteomyelitis with secondary fungal infections involving the maxilla or mandible in patients with a history of SARS-CoV-19 infection can improve prognosis.

COVID-19 associated mucormycosis: A case report in Pakistan and a review of 144 cases.

Mucormycosis is the third most common mycosis in order of its importance as a human pathogen, occurrence of which has become more frequent around the world. Although not proven as a causal association, the increased number of cases has been attributed to Covid-19, the rampant use of corticosteroids, and diabetes. We report the case of a 53-year-old male with mucormycosis related to a Covid-19 infection as the novel case from Pakistan and discuss its epidemiology, diagnostic principles, and management. In our literature review, this is the 145th case being reported with most cases occurring in India, mostly in males, of rhino-orbital form and about a third of them leading to the death of the patient.

Site-Based Comparative Analysis of Sample Collection Through Direct Biopsy and Nasal Swabs for Early Diagnosis of Post-COVID Rhinomaxillary Fungal Infection Using Potassium Hydroxide Mounting: A Retrospective Cohort Study.

Aim: To perform site-based comparative analysis for samples collected from the nasal region and oral cavity subjected to microscopic detection of fungal hyphae in KOH mount in a group of patients with rhinomaxillary mucormycosis. Methodology: Forty patients fulfilled eligibility criteria. The diagnostic outcome of detection of fungal hyphae from the KOH samples obtained was the primary endpoint of the study. Based on this, the samples were grouped into three groups viz-oral, nasal and both. The secondary outcome was to check if there was any diagnostic delay in these three groups of patients. Results: The mean number of days for delayed diagnosis for oral site involvement was 56.33 ± 37.53, for nasal involvement was 32.86 ± 19.53 and for both oral and nasal involvement was 22.00 ± 12.94. This difference was statistically significant at p = 0.03. The mean delay in diagnosis was significantly less when both oral and nasal regions are involved as compared to the only oral region involved at P = 0.01. Conclusion: To avoid the chance of delayed diagnosis or false-negative results, it is best to collect samples from both nasal tissues and the most representative site in the dentoalveolar segment depending on the extensiveness of the disease.

Agents of mucormycosis outbreak associated with COVID-19

Mucormycosis is a life-threatening infection. Mucormycetes causes a wide range of diseases, including pneumonia, rhinosinusitis, internal organ spread, gastrointestinal tract involvement, and skin and soft tissue infection. It infects predominantly with hematological malignancies, transplantation, immunocompromised, and diabetes mellitus patients. The most severe type of the disease is a disseminated disease, which is linked to significant immunosuppression. Currently, this disease is more prevalent in the COVID-19 pandemic because of erroneous steroid use and untreated diabetes. However, there is a scarcity of study and information on the COVID-19 and mucormycosis connection. According to the latest research, mucormycosis cases are rising in developed and developing nations, and only a few therapies are available. The exact burden of mucormycosis is unclear;however, it is likely to be greater than recorded instances due to mucormycosis epidemiological changes. As a result of the delay in identifying this severe illness, appropriate antifungal medications are delayed, resulting in significant morbidity and death. A few drugs are underclinical trials for their efficacy. Other obstacles to treat patients are lack of reliable diagnostic non-invasive tests. This review article draws the attention of its readers and clinicians towards the agents of mucormycosis and discuss the various cases to manage this fungal infection.

Mucormycosis in COVID-19

COVID-19 a global pandemic started in December 2019 and in these last year it has been linked to a range of bacterial, fungal, and viral infections. Mucormycosis sometimes known as black fungus is one of the rare but deadly angioinvaise fungal infection caused by group of fungi mucormycocetes which leads to upsurge of Mucormycosis in COVID-19 patients. Many states in India have declared mucormycosis as an epidemic due to its upsurge in numbers and higher fatality rate. Though mucorales can affect the any part of body but it has tissue tropism towards nasal sinuses, orbit, CNS, pulmonary, skin. Most common clinical presentation of fungi is infection of sinus with nasal blockage and discharge. Mucormycosis is a non-contagious fungal infection, more common in immune compromised patient. Acute inflammatory reactions in COVID-19, corticosteroids treatment and diabetes enfeeble the immunity and it makes the perfect storm for Mucormycosis. Diabetes that isn't well managed results in the acidosis a satisfactory environment for fungi to grow. An early diagnosis and management can decrease the fatality rate. Aim: The goal of this study is to provide a comprehensive overview of the literature concerning Mucormycosis aetiology, features, and management and how it can be prevented in COVID-19 (SARSCoV-2) patients. Conclusion: COVID-19, overuse of corticosteroid along with uncontrolled diabetes leads to an upsurge of mucormycosis. So an effort should be made to stringently monitor and keep the blood glucose level under control and judicious use of corticosteroid and antibiotics should be practiced in COVID-19 patients.

CLINICAL STUDY OF COVID ASSOCIATED RHINO-ORBITAL MUCOR MYCOSIS IN STATE COVID HOSPITAL

Background: Mucormycosis is one such infection which has shown a sudden rise during the second wave in India. (Our present study has been designed to all the confirmed cases of rhino orbital mucormycosis. In our study we have included all the rhinorbital mucormycosis cases that have been confirmed by microscopy and or radiological evidence.Mucormycosis (also called zygomycosis) is a serious fungal infection caused by agroup of molds called mucoromycetes. Materials and Methods: All the patients that have directly attended the ophthalmology OPD. Chief complaint with duration (Look for redness, watering, discharge & pain in the eye, diplopia, eyelid/ periocular swelling) facial swelling, eyelid/perioculay facial discoloration, Worsening headache, sudden drooping of eyelid (or) restricted eye movements, sudden loss of vision, facial parasthesia / anaesthesia, nasal discharge (blakish/ bloody/foul smell nasal stuffiness, dental pain. Results: Out of all 60 cases, 79 there were 47 males and 13 females. In this study 48.33% cases belongs to age group of 50-60 years followed by 36.66% belongs to age group of 60-70 years. Among the 60 patients who presented to hospital within 1 week of onset of symptoms likee pain redness watering et 35 of them got good vision, whereas among the 15 members who presented beyond 2 weeks after the onset of their symptoms only 7 got good vision while 2 of them got poor vision below 6/60 indicating the importance of early diagnosis. 65% cases affected at right eye and 63.33% cases showing symotoms like Redness, treatment under goes with total Restriction 42 members and Painful oculr movement in 43.33% cases. Conclusion: The second wave of COVID-19 in India has led to more deaths than the first. In just a few weeks, the B.1.617.2 (Delta) variant became the dominant strain across India. It has since spread to about 40 nations, which include United Kingdom, Fiji and Singapore.18 the first case of Covid-19-related Mucormycosis has now been found in Chile. It is important to recognise at an early stage this infection, so as to potentially reduce soft and hard tissue necrosis and severe complications and alert colleagues of this mutilating and life threatening infection.

The impact of mucormycosis (black fungus) on SARS-CoV-2-infected patients: at a glance.

The emergence of various diseases during the COVID-19 pandemic made health workers more attentive, and one of the new pathogens is the black fungus (mucormycosis). As a result, millions of lives have already been lost. As a result of the mutation, the virus is constantly changing its traits, including the rate of disease transmission, virulence, pathogenesis, and clinical signs. A recent analysis revealed that some COVID-19 patients were also coinfected with a fungal disease called mucormycosis (black fungus). India has already categorized the COVID-19 patient black fungus outbreak as an epidemic. Only a few reports are observed in other countries. The immune system is weakened by COVID-19 medication, rendering it more prone to illnesses like black fungus (mucormycosis). COVID-19, which is caused by a B.1.617 strain of the SARS-CoV-2 virus, has been circulating in India since April 2021. Mucormycosis is a rare fungal infection induced by exposure to a fungus called mucormycete. The most typically implicated genera are Mucor rhyzuprhizopusdia and Cunninghamella. Mucormycosis is also known as zygomycosis. The main causes of infection are soil, dumping sites, ancient building walls, and other sources of infection (reservoir words "mucormycosis" and "zygomycosis" are occasionally interchanged). Zygomycota, on the other hand, has been identified as polyphyletic and is not currently included in fungal classification systems; also, zygomycosis includes Entomophthorales, but mucormycosis does not. This current review will be focused on the etiology and virulence factors of COVID-19/mucormycosis coinfections in COVID-19-associated mucormycosis patients, as well as their prevalence, diagnosis, and treatment.

Disseminated mucormycosis: An unusual case of ascites with bone marrow invasion.

Mucormycosis is a fatal invasive illness most frequently seen in immunocompromised hosts with uncontrolled diabetes, hematological malignancies, organ transplantation, or long-term steroid treatment. It has a poorer outcome than other fungal diseases due to its rapid spread and resistance to antifungal agents. We report a rare case of disseminated mucormycosis including the bone marrow, peritoneum, lung, and lymph nodes in an apparently immunocompetent 58-year-old gentleman who presented with two months of ascites and weight loss. After a thorough analysis, we found aseptate fungal hyphae in the bone marrow and ascitic fluid. In addition, a cottony white, woolly growth indicative of mucor species was seen in the ascitic fluid culture. CT scans of the chest and abdomen indicate characteristics consistent with mucor invasion. We began the patient on tablet posaconazole, but he died on the fifth day. The atypical presentation in an apparently immunocompetent patient and broad dissemination with rare bone marrow involvement emphasizes the disease's invasiveness.

RHINO MAXILLARY MUCORMYCOSIS IN COVID-19 RECOVERED PATIENT : A CASE REPORT

Mucourmycosis also known as zygomycosis caused by mucorales present in air and soil leads to development of infection in different parts of body common in rhinocerebral area, sinuses, lungs gastrointestinal tract . The maj or risk factor for its development is diabetes mellitus or any other condition which causes immune suppression. It is a lethal secondary infection seen in COVID -19 infected patients.We present a case of 48 year old diabetic COVID-19 recovered patient who was diagnosed as a case of rhinomaxillary mucourmycosis. He was treated with surgical debridement and Amphotericin B along with strict glycemic control. Early diagnosis and treatment can prevent morbidity and mortality in case of mucourmycosis infection.