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Acute Invasive Rhino-Orbital Mucormycosis in a Patient With COVID-19-Associated Acute Respiratory Distress Syndrome
Abstract
Acute invasive fungal rhinosinusitis is a rare, although highly morbid, infection primarily affecting immunosuppressed individuals. The same population is at particularly high risk of complications and mortality in the setting of SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome. The authors present a case of acute invasive fungal rhino-orbital mucormycosis in a patient with COVID-19 and discuss the prevalence, diagnosis, and treatment of fungal coinfections in COVID-19. Prompt recognition, initiation of therapy, and consideration of the challenges of rapidly evolving COVID-19 therapy guidelines are important for improving patient survival.
... New and improved molecular methods are also being widely accepted for confirmation of infection.Histopathology:Demonstration of hyphae in biopsies of affected tissues or bronchoalveolar lavage (BAL) in case of patients with pulmonary infections can be considered confirmatory for diagnosis. Histopathology is very important in diagnosis since it confirms presence of the fungus as a pathogen in the specimen and can also reveal angio-invasion, prominent infarcts and perineural invasion in the affected tissue(Cornely et al., 2014;Mekonnen et al., 2021). Routine hematoxylin and eosin (H&E) staining reveals only the cell wall with no inner structures. ...
... Lesions related to angioinvasive fungal infections like nodules, halo signs, reverse halo signs, cavities, wedge-shaped infiltrates, and pleural effusions are detected easily with the help of CT scan. Proptosis, asymmetry in the retrobulbar fat stranding, opacification of sinuses and erosive lamina papyracea are the notable characteristics in rhino-orbital mucormycosis(Mekonnen et al., 2021).SerologyNo commercial antigen markers are available for detection of -d-glucan test is not sensitive for detection of antigenic determinants of the Mucorales(Cornely et al., 2019). Several serological techniques have been developed for the diagnosis of mucormycosis like ELISA, immunoblots and immunodiffusion tests with variable sensitivity and specificity of detection. ...
Mucormycosis is an infectious fungal disease of humans and animals caused by group of molds in the order Mucorales. The disease is more severe in immunocompromised individuals and route of infection are inhalation, ingestion and direct entry through wounded skin. Among different pathogenic members of Mucorales, most of the infections are caused by the genus Rhizopus. There are numerous risk factors associated with the pathogenesis of the disease like diabetes mellitus, organ transplants, steroid therapy, deferoxamine therapy etc. High incidence has been reported among hospitalized COVID-19 patients. Depending upon the anatomical location, various clinical forms are manifested such as Rhino-orbital-cerebral mucormycosis (ROCM), pulmonary, cutaneous, Indian Veterinary Association, Kerala 151 ISBN No : 978-93-5680-551-4 gastrointestinal (GI) and disseminated mucormycosis, with ROCM being the most common clinical form. Early diagnosis as well as timely and complete treatment protocol are important for proper management of infection. Diagnosis of mucormycosis is very challenging. Along with clinical manifestations, histopathology, direct microscopic examination and culture can provide base for diagnosis of mucormycosis. For further confirmation new and improved molecular methods are also being widely accepted. Antifungal therapy including liposomal Amphotericin B, posaconazole and isavuconazole has been shown to be effective in the treatment of mucormycosis. Sometimes surgical debridement along with antifungal agents may be needed for management of infection.
... COVID-19 is linked to a high rate of secondary fungal and bacterial infections, mostly due to immunological dysregulation. Additionally, the extensive use of broad-spectrum antibiotics, monoclonal antibodies, and steroids as part of the COVID-19 treatment protocol may result in developing or worsening preexisting fungal illnesses [13][14][15]. Physicians should be aware of the likelihood of invasive secondary fungal infections in patients with COVID-19, particularly those with prior risk factors. They should be able to ...
... COVID-19 is linked to a high rate of secondary fungal and bacterial infections, mostly due to immunological dysregulation. Additionally, the extensive use of broad-spectrum antibiotics, monoclonal antibodies, and steroids as part of the COVID-19 treatment protocol may result in developing or worsening preexisting fungal illnesses [13][14][15]. Physicians should be aware of the likelihood of invasive secondary fungal infections in patients with COVID-19, particularly those with prior risk factors. They should be able to detect and treat these infections early, thus reducing mortality and morbidity rates. ...
There has been a notable increase in rhino-orbito-cerebral mucormycosis (ROCM) post-coronavirus disease 2019 (COVID-19), which is an invasive fungal infection with a fatal outcome. Magnetic resonance imaging (MRI) is a valuable tool for early diagnosis of ROCM and assists in the proper management of these cases. This study aimed to describe the characteristic MRI findings of ROCM in post-COVID-19 patients to help in the early diagnosis and management of these patients. This retrospective descriptive study was conducted at a single hospital and included 52 patients with COVID-19 and a histopathologically proven ROCM infection who were referred for an MRI of the paranasal sinuses (PNS) due to sino-orbital manifestations. Two radiologists reviewed all the MR images in consensus. The diagnosis was confirmed by histopathological examination. The maxillary sinus was the most commonly affected PNS (96.2%). In most patients (57.7%), multiple sinuses were involved with the black turbinate sign on postcontrast images. Extrasinus was evident in 43 patients with orbital involvement. The pterygopalatine fossa was involved in four patients. Three patients had cavernous sinus extension, two had pachymeningeal enhancement, and one had epidural collection. The alveolar margin was affected in two patients, and five patients had an extension to the cheek. The awareness of radiologists by the characteristic MRI features of ROCM in post-COVID-19 patients helps in early detection, early proper management, and prevention of morbid complications.
... Diabetes is the most common comorbidity in mucormycosis accounting to 73.5% in India. 6 Most common presentation in our study was unilateral facial pain with proptosis in 80% patients. In the Badie et al study, the most common presentation was hematological disorders (57.2%) followed by diabetes (21.4%). ...
... Recent studies have observed that COVID-19 infected patients who are treated with widespread broad spectrum antibiotics and steroid therapy recovered after secondary bacterial or fungal infections in 8%. 6,8 The most common etiological agent in our study was mucor followed by rhizopus and aspergillus. The commonest fungi isolated in Prakash H et al was Rhizopus (51.9%) followed by mucormycosis. ...
Rhino cerebral Mucormycosis is the current life-threatening infection commonly affecting immunocompromised patients espe-cially post COVID-19 within 6 weeks having poor glycemic control, Intravenous drug users, ICU patients, post chemotherapy, iron overload, persistent neutropenia and follow-up cases of hematological malignancies. It affects the nasal and paranasal sinuses by air-borne spores producing the infection. A prospective case series conducted at the department of pathology, KAMSRC between May 1st to September 30th 2021 with a study population of 27 cases. Variables included age, gender, history of covid, duration and development of symptoms, Clinical presentation, clinical diagnosis, co-morbidities, histopathological examination and microbiological correlation. The most prevalent isolated agent is Mucor (48.1%) followed by Rhizopus (18.5%), Aspergillus (11.1%) and mixed mucor with aspergillus (11.1%). Conclusion: Understanding the mechanism of host innate immunity and specific preventive strategies are important for favorable prognosis. Histopathological examination aids in early diagnosis of Mucormycosis
... Orbital and intracranial extension are associated with increased risk of morbidity and mortality (Baghel et al., 2022;Jung et al., 2009). In some cases, the diagnosis is only done post-mortem (Arana et al., 2021;Hanley et al., 2020;Garg et al., 2021;Pasero et al., 2020;Placik et al., 2020;Bellanger et al., 2021;Zurl et al., 2021;Werthman-Ehrenreich et al., 2021;Monte Junior et al., 2020;Mekonnen et al., 2021;Mehta et al., 2020;Waizel-Haiat et al., 2021). More recent studies reported significantly lower rates of 49% (Arana et al., 2021;John et al., 2021). ...
Purpose: To report a rare case of bilateral sporadic aniridia in an African child and review the management modalities.
Presentation: We report a case of bilateral sporadic aniridia with horizontal nystagmus, axial cataract optic disc, and fovea hypoplasia in a 5-year-old female patient. She was managed conservatively. Various modalities of treatment are reviewed.
Keywords: aniridia, sporadic, nystagmus, cataract, glaucoma, keratopathy, tattooing, syndrome, fovea hypoplasia and optic disc hypoplasia
... Spread of infection from sinuses into mouth and entails necrotic ulcerations over hard palate. 2 ...
Corona Virus Disease 2019 (COVID 19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan city of China in December 2019. Since then, the disease has spread very rapidly which has led to the current pandemic. Secondary infections are reported now a days during the illness in Covid-19 patients of any age and patients recovered from COVID 19. The high-risk conditions prone for opportunistic infections are uncontrolled blood sugar levels, prolonged steroid usage and oxygen therapy. Mucormycosis is highly invasive secondary infection. Early diagnosis along with surgical and medical intervention and control of all risk factors plays a crucial role. Delay in presentation of patient to medical care is really challenging to the physicians and ENT surgeons.
... Diagnostic methods included sinus histopathology, MRI, and CT of the head. [50] 23 ...
... There are case reports of invasive disseminated candidiasis, ROCM, and invasive aspergillosis in COVID-19-infected patients or patients recovering from COVID-19 pneumonia. [6][7][8][9][10][11][12][13] During the pre-COVID-19 era, India had a prevalence of mucormycosis of about 0.14 cases per 1000 population. [14] Diabetes mellitus was the most common underlying condition for mucormycosis, followed by hematological malignancies and solid organ transplant. ...
Severe acute respiratory syndrome coronavirus 2-like other viral infections cause temporary immunosuppressive effects. This COVID-19 infection-induced temporary suppression of cellular immunity can predispose to infections like fungal. Furthermore, high-dose corticosteroids used in COVID-19 management can trigger or accelerate fungal infections. This case series presents the clinicomicrobiological profile of a few such admitted cases, as it is very important for all clinicians and clinical microbiologists to keep the new yet recently not-so-uncommon entities in mind while evaluating a patient.
... There have been numerous case reports of invasive mucormycosis in the context of COVID-19 [25][26][27] and large case series mainly originating from the Indian subcontinent. [12][13][14][15] The incidence and prevalence of COVID-19associated mucormycosis have risen rapidly during the second wave, with the state of Gujarat in India reporting the highest number. ...
Purpose: To investigate oculoplastic conditions in patients diagnosed with coronavirus disease 2019 (COVID-19) seen at ophthalmology departments of three tertiary referral centers in the United Kingdom and the United States, and review of the literature. Methods: Retrospective multicenter case series studied over 18 months. Results: A total of four patients developed eyelid, orbital, or lacrimal gland pathology within four weeks of testing positive for COVID-19. All were male, and the mean age at presentation was 49 (range, 31–58 years). Suspected diagnoses included anterior idiopathic orbital inflammation, facial angioedema, dacryoadenitis, and anophthalmic socket inflammation. Three patients recovered fully and one patient recovered partially (mean 2.7 weeks) from ocular manifestations with steroids hastening recovery. Conclusion: Adnexal manifestations of COVID-19 include self-limiting orbital inflammation and eyelid lymphedema.
... The patient, despite having no prior medical conditions, experienced hyperglycemia and immunosuppression due to corticosteroid injection administered by the researchers. COVID-19-induced immunological dysregulation further exacerbated the emergence of invasive mucormycosis, emphasizing the importance of early diagnosis by healthcare professionals [108] . ...
... 13 Rhizopus invades the epithelium via fungal spore coat proteins (CotH) and binds to the host receptor (GRP78) on nasal epithelial cells. 12 The use of corticosteroids in the treatment of patients with COVID-19 may stimulate the expression of CotH3 and GRP78 by the nasal epithelium, thus facilitating invasion by fungal cells. 7,8 Finally, the recent surge in COVID-19 cases was associated with an unprecedented shortage of oxygen availability, resulting in the use of industrial-grade oxygen in some parts of the country. ...
Background Coronavirus disease-2019 (COVID-19) has been associated with a wide range of opportunistic fungal infections. Many countries have seen an unprecedented rise in cases of COVID-19-associated mucormycosis (CAM). The purpose of this study is to identify the correlation between the COVID-19 epidemic and mucormycosis. Our study also provides details on factors causing CAM. Methods A retrospective study from November 2020 to February 2022 includes four cases of COVID-19-associated rhino-orbital mucormycosis treated at Habib Thameur Hospital’s ENT Department. Results The mean age of patients was 67.5-years, 75% were males, and the most frequent underlying conditions were diabetes mellitus (100%). The median time interval between the diagnosis of COVID-19 and the first evidence of mucormycosis infection was 15-days; two patients required hospitalization in a COVID unit, and two patients received oxygen therapy at home. All patients received corticosteroid therapy at a dose of 1 mg/kg/d for an average of 10-days. Treatment using antifungals and surgery was described in all the patients. Amphotericin B deoxycholate was used in 75% and lipid formulation in 25%. Two patients presented renal insufficiency due to amphotericin B; the doses were adapted with good evolution. In that report, the case fatality rate was 75%. Conclusion Mucormycosis is a fatal fungal infection that usually affects patients with altered immunity. Several cases of mucormycosis in people with COVID-19 have been increasingly reported worldwide. Diabetes mellitus (DM), steroid overdose, immunosuppression, and high iron levels, combined with other factors such as prolonged hospitalization, unhygienic conditions, and the use of ventilators, combine to create an ideal environment for contracting mucormycosis. Lastly, there is a need to create awareness about fungal diseases among clinicians in order to help identify early symptoms and restrict the spread of lethal fungal diseases. A collaborative team of otolaryngologists, ophthalmologists, anesthesiologists, and resuscitators will be required in hospitals to accelerate optimal management.
... There was a strong association between COVID-19 infection and mucormycosis along with presence of diabetes mellitus and other comorbid conditions and a history of hospitalization during COVID-19. Current guidelines also suggest the use of steroids in admitted patients requiring O 2 support [10][11][12][13][14]. In case of aspergillosis, the associated finding during surgery was presence of a fungal ball without tissue invasion [12]. ...
Pott’s puffy tumour is most frequently associated with bacterial infection but fungus causing Pott’s puffy tumour is very rare. A case series of three patients with Pott’s puffy tumour caused by fungi of different species like candida, aspergillus, mucor along with the clinical findings and management is presented here. Keywords: Pott’s tumour; fungal aetiology; puffy tumour
... [1,2,[4][5][6][7] Yet, they stated that COVID-19 when associated with other risk factors such as diabetes mellitus, immunocompromised patients after organ transplantation as well as those with chronic renal diseases, are the precursors for the black fungal infection in agreement with previously published reports. [6][7][8][9][10]17] The dietary and nutritional habits of eating black fungal-infected food plus the inhalation of polluted air believed that these factors to be precursors for the transmission of infection. Such a concept was supported by other research studies. ...
Background:
During the coronavirus (COVID-19) global pandemic, the diagnosis of mucormycosis co-infection has become challenging as it is sometimes misdiagnosed or even undiagnosed. Many factors contribute to acquiring such infections. These factors vary but their main reason for getting such infections is being immunocompromised. Thus, it results in weak host immunity to fight and prevent such co-infection.
Objectives:
This study aims to assess the knowledge perception among the general population in Saudi Arabia regarding black fungus and its relationship with the global pandemic COVID-19.
Materials and Methods:
A prospective, qualitative, questionnaire-based cross-sectional study took place. The obtained data were statistically analyzed using SPSS version 21.
Results:
The study included 1138 participants, 31.5% from southern region, 27.8% from Eastern region, 22.2% from north region, 12.2% from Western region, and 6.3% from Central region. The participant's mean age was 27.1 ± 11.9 years old. A good knowledge level was detected among 35% of female respondents compared to 28.9% of males with reported statistical significance (P =0.036). All other factors including age, education, and work were insignificantly associated with public knowledge level.
Conclusions:
A considerable percentage of the current study population had poor knowledge level of perception and awareness regarding mucormycosis in relation to COVID-19.
... [1,2,[4][5][6][7] Yet, they stated that COVID-19 when associated with other risk factors such as diabetes mellitus, immunocompromised patients after organ transplantation as well as those with chronic renal diseases, are the precursors for the black fungal infection in agreement with previously published reports. [6][7][8][9][10]17] The dietary and nutritional habits of eating black fungal-infected food plus the inhalation of polluted air believed that these factors to be precursors for the transmission of infection. Such a concept was supported by other research studies. ...
Background
During the coronavirus (COVID-19) global pandemic, the diagnosis of mucormycosis co-infection has become challenging as it is sometimes misdiagnosed or even undiagnosed. Many factors contribute to acquiring such infections. These factors vary but their main reason for getting such infections is being immunocompromised. Thus, it results in weak host immunity to fight and prevent such co-infection.
Objectives
This study aims to assess the knowledge perception among the general population in Saudi Arabia regarding black fungus and its relationship with the global pandemic COVID-19.
Materials and Methods
A prospective, qualitative, questionnaire-based cross-sectional study took place. The obtained data were statistically analyzed using SPSS version 21.
Results
The study included 1138 participants, 31.5% from southern region, 27.8% from Eastern region, 22.2% from north region, 12.2% from Western region, and 6.3% from Central region. The participant's mean age was 27.1 ± 11.9 years old. A good knowledge level was detected among 35% of female respondents compared to 28.9% of males with reported statistical significance ( P =0.036). All other factors including age, education, and work were insignificantly associated with public knowledge level.
Conclusions
A considerable percentage of the current study population had poor knowledge level of perception and awareness regarding mucormycosis in relation to COVID-19.
... Patients with neutropenia, Diabetics, hematologic malignancies, people on systemic corticosteroids use, hematologic malignancies, immunocompromised persons and stem cell transplant patients, are all susceptible to mucormycosis [45]. According to reports, patients with diabetes seem to be more likely to get COVID-19 and become infected with mucormycosis [46]. Diabetes may increase COVID-19 morbidity and mortality by the following mechanisms: 1-reduction in T-cell activity, 2-decreased viral clearance 3-immune-suppression, and 4increased storm of cytokine [20]. ...
... 10 Uncontrolled diabetes mellitus, chronic use of steroids, candidates receiving organ transplants, neutropenia, and hematological cancers are risk factors for mucormycosis. [11][12][13] To control the infection in patients with COVID-19-associated rhino-orbital mucormycosis (CAROM), aggressive and multiple radical debridement is necessary, along with antifungal therapy. 14 As a result, these patients are left with extensive facial defects, including missing orbital, mandibular, and palatal components, which lead to significant functional losses such as nasal breathing, oral feeding, and comprehensible speech. ...
Background In India, between May 5 and July 2021, 41,512 cases and 3,554 deaths due to mucormycosis were reported in coronavirus disease 2019 (COVID-19)-infected patients or COVID-19-recovered patients. COVID-19-associated rhino-orbital mucormycosis (CAROM) has been associated with adverse effects that can affect oral health, vision, and physical as well as emotional functioning. After the radical debridement of CAROM and antifungal therapy, reconstructive surgery should be employed to restore function and aesthetics; however, limited clinical data exist on its potential effect on the quality of life (QOL) of these patients.
Objective Our objective was to assess the QOL among CAROM patients reconstructed with free flap surgery.
Materials and Methods This analysis studied 19 patients of CAROM who had maxillectomy and/or orbital exenteration defects reconstructed with free flaps at a tertiary care center. All these patients were free from any residual disease, as confirmed by tissue biopsy taken from the affected area. The QoL of these patients was assessed 1 week preoperatively and 4 to 6 months postoperatively using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-HN43) questionnaire module.
Results There was a statistically significant improvement in 10 out of the total 19 parameters ( p < 0.05) which include pain in the mouth, problems opening mouth, speech, swallowing, weight loss, dry mouth and sticky saliva, body image, fear of progression, social contact, and social eating.
Conclusion The EORTC QLQ-HN43 questionnaire module presented a statistically significant improvement in the functional as well as psychological status of the CAROM patients undergoing reconstruction by free flap surgery.
... Several studies have found that patients with diabetes mellitus are more likely to develop COVID-19 and, subsequently, mucormycosis. COVID-19 morbidity in diabetic patients may be caused by a loss in T-cell activity, a decrease in viral clearance, immunological suppression, or a high cytokine storm [7][8][9][10]. Therefore, diabetic patients are at an increased risk of developing mucormycosis. ...
Background
Mucormycosis is an opportunistic infection that mainly affects immunocompromised individuals, including those with uncontrolled diabetes, malignancies, or those who have exposure to high-dose corticosteroids for a long time. Western Odisha, India, witnessed a significant rise in post-COVID-19 rhino-orbital mucormycosis (ROM), which created a need for comprehensive research on post-COVID-19 ROM.
Objective
This study aimed to investigate the prevalence, clinical characteristics, and outcomes of post-COVID-19 ROM in a tertiary care hospital in Western Odisha, India, with the objective of understanding ROM as a nationally notifiable disease.
Subjects and methods
A prospective hospital-based study was conducted. Mucormycosis cases were reported within the period, from May 17, 2021, to July 31, 2021, including all post-COVID-19 patients who exhibited clinical manifestations of mucormycosis. Patients with histopathologically negative reports of mucormycosis were excluded.
Results
Of the 35 included, 25 were diagnosed with ROM. The age group of 46-50 years showed a predominance (n=6), with a mean age of 50.53 years. The male-to-female ratio was 2:1. Specifically, 88% of the patients included had diabetes mellitus, 8% had chronic kidney diseases, 8% had sepsis, and 4% had hypertension. ROM was the predominant manifestation (60%, n=15), with the majority presenting with orbital cellulitis (80%), followed by unilateral orbital apex syndrome (12%), bilateral orbital apex syndrome (4%), ophthalmic vein involvement (4%), and osteomyelitis of the maxillary sinus (4%). Irrigation of the wound was performed, and all 25 ROM patients received IV liposomal amphotericin B (L-AMB).
Conclusion
Post-COVID-19 status with elevated blood sugar levels was a major risk factor for ROM. Early diagnosis, debridement, L-AMB, retrobulbar AMB deoxycholate, and exenteration are the possible solutions.
... Based on the anatomical site clinical investigation, Mucormycosis has six categories: (i) rhinocerebral, (ii) pulmonary, (iii) cutaneous, (iv) gastrointestinal, (v) disseminated, and (iv) miscellaneous (Spellberg et al., 2005). Rhinocerebral disease, a form of mucormycosis, is commonly observed in severely diabetic or dehydrated individuals (Pillsbury and Fischer, 1977), and Acute invasive fungal rhinosinusitis primarily infects immunosuppressed individuals (Mekonnen et al., 2021). ...
Objective. Mucormycosis is a fungal infection in humans where the causative pathogens belong to the order of Mucorales. The fungal pathogens are also known as black fungi based on morphological characteristics. Mucormycosis is increasingly observed in patients suffering from the COVID-19 virus from different states of India, wherein steroids are being used as standard therapy. The prevalence of coronavirus disease and the infection by the black fungus (Mucormycosis) poses several challenges to its mitigation. The purpose of the study is to analyze the research trends of mucormycosis using bibliometric methods. Design/Methodology/approach. The study utilizes standard bibliometric methods to analyze bibliographic literature on Mucormycosis retrieved from the SCOPUS database. All keywords (MeSH terms) associated with Mucormycosis were used to frame a search query and retrieve bibliographic data from the database. The bibliometric indicators were used to assess research productivity in mucormycosis for publication growth; subject distribution; productive authors, institutes, and countries; journals, highly cited articles; and hot spots and research progress based on the keyword analysis. VOSviewer network visualization tools have been used for mapping research. Results/Discussion. The analysis of 25,251 bibliographic records shows exponential growth in literature during seventy years. Though mucormycosis research is spread across the globe, the prevalence of the study is widespread in the SouthEast Asian region. Author keyword analysis shows that the research focuses on the medical subject and expands into multidisciplinary research areas. Conclusion. Bibliometrics always provides insight into the research progress in any field or topic of study. This study provides insight into research progress in Mucormycosis. The researcher may use the results to analyze different areas of mucormycosis and utilize the key concepts for further research, especially researching better clinical practices and drug developments. Originality/Value. Through this paper, it is quite clear that the appearance of research contribution on mucormycosis coupled with COVID-19 has opened a new direction of research that clinical researchers take up in future research.
... Due to impairment of poly morpho nuclear cells in diabetics, it is also difficult to prevent the spread of Mucorales resulting in extensive invasion of tissues and blood vessels. Similar findings of diabetic patients getting COVID-19 infection leading to mucormycosis had been presented by other researchers too (8,(17)(18)(19)(20). Out of 51 patients, 33were giving a recent history of COVID-19 infection. ...
Introduction: As the number of COVID-19 patients increased during second wave, a steep rise of patients with mucormycosis was found in all parts of India. Objectives: To determine the epidemiological factors leading to the rise in fungal infection in patients during COVID-19 pandemic as well as describe the outcome of the disease during next three months after being discharged from the hospital Methods: It was a concurrent prospective study conducted between 26 June to 25 October 2021 at ESIC Medical College & Hospital, Faridabad, India. Patients positive for mucormycosis and agreed for the study were enrolled. They were interviewed telephonically after recording their consent. Results: A total of 51 patients were interviewed during our study period. During the follow-up, six patients died within three months of discharge from the hospital. The mean age of patients was 49.6years (SD=6.9 years), with the majority in the age group of 41-60 years. Most (53%) of the patients were males and 30(58.8%) were graduates and above. In the sample, 33 had a recent history of COVID-19 infection, 24 (47%) had been prescribed steroids, 16 (31.3%) had been prescribed oxygen during COVID-19 infection and 33(64.7%) were diabetic. The relationship of potential risk factors with the type of mucormycosis was not found to be statistically significant. Out of the45 patients who survived, 35 were better, three were still on oral anti-fungal treatment and seven patients required reconstructive plastic surgery. A significant association was found between patients who had a history of steroid intake and type of mucormycosis. Conclusions & Recommendations: Patients admitted to hospital with mucormycosis during the COVID-19 surge mostly had a history of COVID-19 infection, suffering from diabetes or on steroids. Most of the patients survived due to treatment availability (antifungal medicines, surgery or both) and about 15% of them had undergone long debridement surgery leading to severe loss of normal contour of the face and waiting for plastic reconstructive surgery.
... Mekonnen et al. reported a case of invasive fungal sinusitis in a Covid 19 patient with opacification of the unilateral paranasal sinuses, lamina papyracea dehiscence, right orbital proptosis, and cellulitis [8]. In a case series of six patients by Sen et al. one of the patient had concurrent Covid 19 and rhino-orbital mucormycosis. ...
The base of skull forms the first line of barrier to be breached in the transition of rhino-orbito-palatal forms of mucormycosis to intracranial forms with various neurological deficit. The pattern of base of skull erosion has prognostic implications in overall recovery and survival of the patient. The aim of the study was to assess the pattern of skull base involvement in cases of rhino-orbital-cerebral mucormycosis (ROCM) in terms of clinical presentations, radiological findings, intraoperative illustrations and post operative recovery. This is a retrospective single centre study of Covid associated Mucormycosis (CAM) patients with skull base involvement at a tertiary referral centre of central India from May 2021 to October 2021. Amongst a total of 248 patients of CAM, 54 patients with skull base involvement were included in our study. The cases were stratified into basifrontal-BF (15%), basisphenoid-BS (20%), orbital apex-OA (15%), basiocciput-BO (26%), frontal bone osteomyelitis-FBO (22%) and sphenoid bone osteomyelitis-SBO (2%), based on their pattern of involvement of skull base and intracranial spread. Early ethmoid and cribriform plate involvement progressed to frontal lobe abscess while early maxillary disease progressed to developed temporal lobe abscess. The orbital apex lesions had early onset cavernous sinus thrombosis. Analysis of clinical manifestations and postoperative follow up revealed an emerging pattern where Posterosuperior lesions of paranasal sinuses (Ethmoid, roof of maxilla and orbit) progressing to BF, BS, OA, FBO and SBO had poorer treatment outcome than Anteroinferior (Floor of maxillary sinus, palate) based lesions which involved BO of skull base. The inferiorly located diseases had better prognosis, less duration of hospital stay, lesser mortality and decreased need for second surgery. There exists a temporal relation of the initial site of fungal load in sinonasal region to their subsequent intracranial spread. Classification into subtypes helped in disease stratification which helped in prognostication and surgical planning. Early intervention by multidisciplinary team improved survival outcome.
... early. [25][26][27][28][29]. ...
... Maxillofacial or rhino maxillary mucormycosis begins with inhalation of the fungus by an immunocompromised individual [9]. There is only few reported rhino-ocular-cerebral mucormycosis associated with COVID-19 infection [5,10,11]. One study of odontogenic mucormycosis was described by Saidha PK et al. [12] with six histo-pathologically proven cases and association with poorly controlled diabetes. ...
Aim of our study was to report unusual presentation of mucormycosis in patients, who were recovered from COVID-19 infection. This was a prospective observational study, undertaken at Ravindra Nath Tagore Medical College, Udaipur, India, over a period of last 3 months (April-June 2021). All patients with maxillofacial and dental mucormycosis were included in the study. All patients either have COVID-19 infection or recovered from it. Eight (40%) patients had history of use of corticosteroids for COVID1-19 infection, fifteen patients had either known case of diabetes or newly diagnosed diabetes with uncontrolled blood sugar at the time of presentation, three (15%) patients were in pre-diabetic state with HbA1c between 6.0 and 6.5% and two patients had no diabetes. None of patients had diabetic ketoacidosis and only one patient reported complete loss of vision with dental symptoms. There was unusual presentation of mucormycosis in form of loosening of teeth in uncontrolled diabetes. Injudicious use of steroids and uncontrolled diabetes are two main risk factors, so eyes should be kept on both of these.
... The recovery rate is poor (20% and 50%) and is further dampened by cranial or orbital involvement, immune compromise, and DKA. [52] Classical signs of onset of rhino-orbital-cerebral mucormycosis (ROCM) are unilateral facial discomfort or edema, visual disturbances, and ocular inflammation resembling conjunctivitis. [53] ROCM spreads to the oral cavity, maxilla, palate, nose, paranasal sinuses, and finally into the central nervous system [54] [Figures 3 and 4]. ...
The last 2 years has been highly tumultuous with the advent of the 2019 novel coronavirus disease (nCovid-19). This viral infection has been a global landmark event in the history of mankind with its standout characteristics such as high transmission rate, initial asymptomatic period, and unexpected systemic outcomes. The long-term damage of this disease is still being unraveled with a profound impact on the global economy and livelihood of millions as well. A literature search was performed with the following keywords – Coronavirus, COVID-19, SARS-CoV-2, 2019-nCoV, Mucormycosis, and Opportunistic infections – in PUBMED/MEDLINE database to assimilate articles/case reports/books about nCovid19 and mucormycosis. nCovid19 data were collected from the Centers for Disease Control and Prevention and Ministry of Health and Family Welfare websites also. This review describes the etiopathogenesis of nCovid19, including the mutation and origin of variants seen so far. We recapitulate existing knowledge of clinical features, investigations, and treatment strategies followed. The various complications seen in nCovid19 recovery patients are also elaborated with a focus on the alarming surge of mucormycosis and mortality in post-nCovid19-affected persons.
Mucormycosis is a life-threatening fungal infection with high morbidity and mortality, particularly affecting immunocompromised individuals. Despite its growing clinical significance, its true global prevalence remains unclear. This systematic review identifies the key risk factors, epidemiological trends, and clinical challenges associated with mucormycosis. A comprehensive literature search was conducted to analyze global case reports, underlying predisposing conditions, and regional variations in disease manifestation. The leading risk factor in developed nations is hematological malignancies, while uncontrolled diabetes mellitus dominates in regions like India. Environmental and climatic factors influence fungal exposure and disease progression. Diagnosis remains challenging due to nonspecific symptoms, contributing to delayed treatment and poor outcomes. Early recognition of risk factors and improved diagnostic strategies are critical to reducing mucormycosis-related mortality. Public health initiatives must prioritise awareness, especially in high-risk populations. Further research is needed to address gaps in treatment and prevention.
The main objective of the current systematic review was to compile and evaluate the data on opportunistic maxillofacial mycotic infections in COVID-19 patients during the treatment and post-recovery period of SARS-CoV-2 infection. Comorbidities like diabetes, corticosteroid use, and mortality among COVID-19-associated patients presenting with oral and maxillofacial fungal infections were also assessed. The review was conducted in accordance with Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. A comprehensive search was carried out in the archives of Web of Science, Pubmed/Medline, Scopus, Google Scholar, Lilacs, and Livivo in combination with Boolean operators till 24th June 2022, and cross-sectional studies, case series, and case reports deliberating on maxillofacial mycoses in COVID-19 were included. The included studies were meted to the risk of bias using the Joana Briggs Institute Appraisal tools for prevalence studies, case series, and case reports. In a two-stage collection, 20 studies were included: 9 observational (3269 patients), 5 case-series (42 patients), and 6 case reports (8 patients) from 7 countries. Mucormycosis was the most commonly reported maxillofacial fungal infection (96.7%/3162 cases), followed by candidiasis (3.2%/105 cases) associated with COVID-19. Although aspergillosis was observed in only one case and one patient, a mixed mycotic infection demonstrating both aspergillus and mucor fungal elements was identified in one patient. Comorbidities like diabetes mellitus, indiscriminate corticosteroid use and immunosuppression leads to invasive maxillofacial fungal infections in COVID-19, which may prove to be fatal.
Background: Mucorales, the causative agent of mu-cormycosis, is a life-threatening fungal infection that primarily affects immunocompromised hosts. This condition is becoming more severe during the current COVID-19 pandemic. The objective is to decipher the link between mucormycosis, steroids, and the associated co-morbidities of COVID-associated mucormycosis (CAM). This study is focussed on assessing the various aspects of COVID related mucormycosis. Aim: To systematically review the reported cases of CAM, clinical presentation with steroid therapy and associated comorbidities.Materials and Methods: MeSH terms like mucormycosis, diabetes, SARS-CoV-2 infection, sinus, orbit, and palate were searched in the PUBMED and Google Scholar databases, and 20 case reports and case series were identified.Results: We found that India had the highest number of cases (60%), 55% of the infected patients were male, 65% had a history of diabetes and the associated risk factor was uncontrolled diabetes (90%). The common clinical presentation among the cases was noted to be necrosis and swelling, with 55% of the cases reported to be rhino orbital mucormycosis. In most of the cases cytological and histological examination had been performed with haematoxylin & eosin, KOH, lactophenol cotton blue, and special stains such as PAS and GMS had been used in few cases along with culture in Sabouraud dextrose agar. Regarding treatment, 85% of the cases were treated with amphotericin B and in 15% of cases a combination of amphotericin B and posaconazole was employed. The rate of mortality reported was estimated to be 25%.Conclusion: COVID-19 infection poses a significant threat to diabetic patients, increasing their susceptibility to mucormycosis. Therefore, the careful use of steroids and routine monitoring are essential in preventing this invasive infection.
Introduction: Rhino-orbital Cerebral Mucormycosis (ROCM) is a rare invasive fungal infection that generally affects diabetic and immunocompromised individuals. There has been a recent rise in mucormycosis associated with SARS-CoV-2 infection even in non-diabetics. Diabetes, malignancy, transplant, chronic renal insufficiency and iron overload are established risk factors for the infection. This deadly disease demands prompt diagnosis and management to prevent mortality. Aims and objectives: 1. To study the risk factors predisposing to mucormycosis in previously non-diabetic patients 2. To study the varied presentations and management of mucormycosis in non-diabetic patients Material and methods: All the patients of mucormycosis who were admitted from May 2021 to December 2023 and who were previously non-diabetic were included in the study. Risk factors causing mucormycosis were studied. Various forms in which mucormycosis presents and their management were studied. Result: Fifty SARS-CoV-2-positive patients were studied, and male predominance was observed with mean age being 64 years. All the patients had normal fasting and post-prandial blood glucose levels done within the last three months. 30 patients had recently been diagnosed with deranged blood sugar levels. Four patients were HCV positive; two were HBsAg positive, two were active cases of tuberculosis, two had recently diagnosed chronic renal failure, two patients had acute myeloid leukaemia, two had chronic lymphocytic leukaemia and two were known cases of Inflammatory bowel disease. Two patients had hypothyroidism, on thyroxine treatment for the past 4 years. In two patients, ferritin overload and vitamin D deficiency were found. Only 14/50(28%), received dexamethasone during covid-19 treatment. Ten patients out of 50(20%) had a history of oxygen support. All underwent debridement and received systemic liposomal Amphotericin B therapy. Two patients (4%) underwent skin debridement for cutaneous mucormycosis. Conclusion: We hereby conclude that the recent surge in cases of mucormycosis was due to multiple factors apart from diabetes alone. We recommend restricted use of steroids (only guideline-based in critically ill patients) and strict monitoring for invasive mucormycosis in post-COVID-19 patients. Additionally, other risk factors that predispose the patients to mucormycosis such as Hepatitis, organ transplant, iron overload, hypothyroidism, and tuberculosis should also be kept in mind.
Os fungos anemófilos são encontrados no ar atmosférico e podem causar ao homem, diversos problemas de saúde. Nesse sentido, objetivou-se, com este estudo, verificar a microbiota fúngica anemófila de um hospital público de Cuité-PB, Brasil. Foram expostas duas placas de Petri, por ambiente, contendo Ágar Sabouraud Dextrose, a um metro do chão, por 15 minutos, na Recepção, Sala de Triagem, Posto de Enfermagem I, Clínica Cirúrgica 111, Farmácia e Enfermaria Infantil, além da área externa do hospital. Além da contagem das unidades formadoras de colônias fúngicas, identificou-se os fungos por suas características macro e micromorfológicas. Verificou-se que todos os ambientes internos investigados estavam de acordo com o preconizado pela Agência Nacional de Vigilância Sanitária, quanto à qualidade do ar interno, exceto a recepção, que ultrapassou 750 UFC/m3. Dentre as espécies fúngicas mais prevalentes, predominaram leveduras (36 UFC – 37,1%), Cladosporium spp. (29 UFC - 29,8%) e Fusarium spp. (11 UFC – 11,3%). Algumas das espécies identificadas, como Aspergillus sp. e Rhizopus sp., apresentam potencial patogênico e/ou toxigênico, inclusive tendo vários casos de coinfecções sido relatadas em pacientes com COVID-19, muitas vezes letais. Pode-se concluir que o Hospital se encontra dentro do esperado, em termos de qualidade do ar, tendo como critério a análise dos fungos anemófilos e que se faz necessário manter os protocolos de limpeza e desinfecção atualizados, para minimizar os riscos à saúde humana.
Mucormycosis is a life-threatening fungal infection caused by fungi of the order Mucorales. It usually affects people with weakened immune systems, such as those with uncontrolled diabetes, acquired immunodeficiency syndrome, iatrogenic immunosuppression, and hematological malignancies, as well as individuals who have had organ transplants. The type of mucormycosis a person suffers from is often determined by their underlying conditions. The most common types are rhino-cerebral mucormycosis, pulmonary mucormycosis, cutaneous mucormycosis, cerebral mucormycosis, gastrointestinal mucormycosis, and disseminated mucormycosis. The incidence of mucormycosis has been increasing over the years, with an overall mortality rate of 54%. Recent cases have shown a correlation between COVID-19 and mucormycosis. Using anti-inflammatory drugs to combat the cytokine storm associated with COVID-19 can weaken the immune system, making individuals more susceptible to opportunistic fungal infections like mucormycosis. Underlying health conditions further exacerbate the condition. This study reviewing 198 cases of mucormycosis and conducting a meta-analysis found that post-COVID-19 patients most commonly developed rhino-orbital-cerebral mucormycosis, followed by pulmonary and gastrointestinal mucormycosis. The study also identified diabetes as the most common underlying factor contributing to the development of mucormycosis in post-COVID-19 patients, followed by hypertension and obesity. The study also examined the influence of age, affected organs, and the use of certain drugs on the development of mucormycosis. Age was found to be a significant factor in the infection. This meta-analysis is one of the first to compare post-COVID mucormycosis cases with those from the pre-COVID era. The hope is that this study and analysis will help identify the determinants of mucormycosis in post-COVID patients and aid the scientific community in finding a solution to this problem.
Introduction
Mucormycosis is an emerging fungal infection associated with high mortality, especially in post-COVID state. Mucormycosis, though fungal spores ubiquitous in the environment, is a clinical disease that occurs in immunocompromised conditions. However, the incidence of mucormycosis is enormously increased in post-COVID-19 infections and in those who are immunocompromised. It presents as rhino-orbital-cerebral mucormycosis. The diagnosis is done by KOH mount and culture on Sabouraud dextrose agar (SDA). The identification of post-COVID risk factors, clinical features, and KOH mount helps in early diagnosis. Early treatment helps in preventing progressive tissue invasion, surgical debridement and thus improves the outcome.
Aims and Objectives
To establish etiological agents of mucormycosis.
To establish the relation of diabetes mellitus, steroid usage, oxygen inhalation, and other risk factors in postCOVID patients suspected with mucormycosis.
To study and establish associated high-risk factors for the sudden explosion of mucormycosis cases in post-COVID state.
Material and Methods
The study was done on a total of 81 patients of suspected mucormycosis admitted at MGM Hospital and 20 controls of post-COVID patients over a period of 3 months. Demographic features, predisposing conditions, clinical features, culture characters, and radiological features were all obtained and analyzed.
Results
The history of diabetes mellitus, steroid usage, and oxygen inhalation were analyzed. Among 81 debrided tissue samples received, 52 were KOH mount positive and out of them only 32 showed growths on SDA. Among them, 9 were Rhizopus , 13 were Mucor , and 10 were other species.
Conclusion
Mucormycosis is a rare and uncommon disease in the past; However, in the COVID-19 pandemic, its association with post-COVID state is established. The common presentation of rhino-orbital-cerebral mucormycosis is dreadful; however, early diagnosis and prompt treatment in time will decrease mortality and morbidity remarkably.
Background: Fungal coinfections have been part of the complications in coronavirus disease (COVID-19) patients. While systematic reviews on individual fungus was available, comprehensive data on the occurrence of various fungal infections was limited. Methodology: A systematic search in the databases ‘PubMed’ and ‘Global Research Database on COVID-19 by the World Health Organization (WHO) was made using relevant search terms. Only fungal coinfections/superinfections in confirmed COVID-19 cases were considered. All observational studies, case series, and case reports in English were included. Overall, the occurrence of the fungal infections and the associated factors was noted. Chi-square and Fisher’s exact tests compared epidemiological factors between survived and dead. Results: Data from 126 eligible studies reporting 870 cases showed that mucormycosis was the most common infection (42.5%), followed by aspergillosis (32.41%) and candidiasis (22.87%). The majority of the infections were seen in severe COVID-19 (94.01%), in ICU (67.25%), and with mechanical ventilation (73.61%). Prior steroid therapy was seen in 81.3% in mucormycosis. In aspergillosis, mechanical ventilation, infection due to Aspergillus fumigatus and administration of steroids at more than the recommended dose were significantly associated with those who died (p<0.05). Conclusion: Mucormycosis, followed by invasive pulmonary aspergillosis and invasive candidiasis, has been the most common coinfections/superinfections in COVID-19 patients. Early diagnosis led to better survival in Covid associated mucormycosis (CAM); however, in COVID-19-associated pulmonary aspergillosis (CAPA), mechanical ventilation, larger doses of corticosteroids than recommended and infection with A. fumigatus were significant associations among those who succumbed to the condition.
Mucormycosis is commonly known as black fungus disease. This disease principally targets diabetic and immunecompromised patients.The main purpose of this review article is to create awareness and to get preventive measures for Mucormycosis. From this, immediate treatment is required for affected person. Symptoms, causes and analysis are investigated to know the individual is impacted for Mucormycosis after COVID.
Objective: The aim of this review literature is to collate and analyse various case reports and series reporting mucormycosis in COVID and post-COVID patients in India and worldwide. Methods: A systematic literature search was conducted from December 2019 to June 2021 using keywords. Details of all the case reports/ series that reported rhino-orbital-cerebral mucormycosis in COVID and post-COVID settings were retrieved and analysed.Results: In this systematic review, 33 articles were included and a total of 181 cases of mucormycosis in COVID and post-COVID patients were reported. Mucormycosis was predominantly seen in males (71.2%) as compared to females (28.7%). History of steroid use was present in 113 patients (62.4%). Type 2 diabetes mellitus was the most common independent risk factor, present in 138 patients (76%). Sino-nasal involvement was seen in 27 patients (14.9%), rhino-orbital involvement in 114 patients (62.9%), andrhino-orbital-cerebral involvement was observed in 40 patients (22%). Improvement in clinical status was observed in 106 patients (58.5%) while 38 patients (21%) expired. Conclusions: A rapid rise in cases of mucormycosis had been reported in the COVID era. Unwarranted use of steroids coupled with uncontrolled hyperglycemia, unregulated activation of inflammatory mediators and overactivation of entry-point receptors inflicted by the Coronavirus cause a state of immune dysregulation, leading to opportunistic invasive fungal infections. A delay in diagnosis can result in disfigurement, functional loss, or even death. Multidisciplinary management with prompt reversal of risk factors is recommended.
Background
Mucormycosis is a rare disease with scarce diagnostic methods for early intervention. Available strategies employing direct microscopy using calcofluor white-KOH, culture, radiologic, and histopathologic testing often are time-intensive and demand intricate protocols. Nucleic Acid Amplification Test (NAAT) holds promise due to its high sensitivity combined with rapid detection. Loop-mediated isothermal amplification (LAMP) based detection offers an ultrasensitive technique that does not require complicated thermocyclers like in PCR, offering a straightforward means for improving diagnoses as a near-point-of-care test.
Methods
The study introduces a novel magnetic nanoparticle-based LAMP assay for carryover contaminant capture to reduce false positives. Solving the main drawback of LAMP-based diagnosis techniques. The assay targets the cotH gene, which is invariably specific to Mucorales.
Results
The assay was tested with various species of Mucorales, and the LODs for Rhizopus microsporus, Lichtheimia corymbifera, Rhizopus arrhizus, Rhizopus homothallicus and Cunninghamella bertholletiae were 1fg, 1fg, 0.1pg, 0.1pg, and 0.01 ng respectively. This was followed by a clinical blindfolded study using whole blood and urine samples from 30 patients diagnosed with Mucormycosis. The assay has a high degree of repeatability and had an overall sensitivity of > 83%.
Conclusions
Early Mucormycosis detection is crucial, as current lab tests from blood and urine lack sensitivity and take days for confirmation despite rapid progression and severe complications. Our developed technique enables the confirmation of Mucormycosis infection in less than 45 minutes, focusing specifically on the RT-LAMP process. Consequently, this research offers a viable technique for quickly identifying Mucormycosis from isolated DNA of blood and urine samples instead of invasive tissue samples.
From the beginning of the COVID-19 pandemic, the incidence of secondary infections (both bacterial and fungal) has increased due to immune suppression associated with the use of corticosteroids or broad-spectrum antibiotics as a part of COVID-19 treatment protocol, which may exacerbate a pre-existing fungal disease or cause a new infection. Ophthalmologists are often involved in taking medical and surgical decisions in these complex cases. In this regard, a strong clinical suspicion should be applied to possible secondary fungal infections in COVID-19. Their early diagnosis and treatment may reduce mortality due to COVID-19 associated rhinocerebral mucormycosis (ROCM). This article describes two clinical cases of late detection of ROCM with two different scenarios, and compare the features of these cases with the literature data.
Purpose of Review
This meta-analysis aimed to identify the CAM manifestations, clinical presentations, relevant risk factors, mortality risk factors, treatments, outcomes, and survival.
Recent Findings
COVID-19-associated mucormycosis (CAM) increased dramatically, with mucormycosis development estimated to be 50 times higher than before the COVID-19 pandemic. CAM is a high-mortality disease with significant morbidities in survivors. A significant association between uncontrolled diabetes and CAM has been indicated. In addition, high-dose corticosteroid therapy and ICU admission were present in many rhino-orbito-cerebral mucormycosis (ROCM) patients and non-ROCM, respectively. In the present study, we systematically searched PubMed, Scopus, WoS, and PMC, preprint databases, and the reference lists of the included relevant studies until Oct 2021. Studies that report mucormycosis cases (proven/probable) with individual patient details with confirmed COVID-19 infection were included according to the PRISMA statement. Pooling data of 210 CAM patients (proven, 87.6%; probable, 12.4%) was retrieved from 60 case reports/series studies from 17 countries.
Summary
Primary or corticosteroid-induced diabetes was the leading independent risk factor for rhino-maxillo-orbito-cerebral mucormycosis (RMOCM) development (OR:18.29). In contrast, ICU admission was the main independent risk factor for non-RMOCM development (OR:11.64). In the absence of the mentioned risk factors, the risk of CAM is low (3.33%). CAM mortality was high (43.5%), with significantly higher fatality in non-RMOCM (77.3%). Severe/critically ill COVID-19 (OR: 3.66), ICU admission (OR: 6.78), and mechanical ventilation (OR: 6.27) were associated with a higher risk of CAM mortality. Cerebral and orbital involvement increased mortality (OR: 3.253 and OR: 3.205) in RMOCM patients; conversely, the surgical intervention improved outcomes (OR: 18.922). Control of hyperglycemia and COVID-19 infection and evidence-based corticosteroid therapy is essential to prevent CAM development. Identifying and controlling the preexisting/predisposing and mortality risk factors of CAM combined with the implementation of aggressive evidence-based management with a multidisciplinary approach can reduce CAM-related morbidity and mortality. An update to the traditional mucormycosis classification was also introduced to refer to maxillary involvement.
Along with the growing number of fatalities and lack of specific treatment at the time, the increasing incidence of mucormycosis worried world health agencies, as it ran the risk of more threatening outcomes for COVID-19 patients. In this context, this review aims to assemble case reports of COVID-19 associated mucormycosis and discuss virulence and host factors involved in the progress of these infections – key aspects that might unveil biological targets and pharmacological approaches to treat these infections. Recently, elevated serum iron levels during SARS-CoV-2 infection have been reported in the literature. Besides being a clinical characteristic of diabetic patients, iron overload is described as a risk factor for Rhizopus oryzae infection. Furthermore, the increased expression of human heat-shock protein GRP78 during iron overload and coronavirus infection display a crucial role as a mediator in Mucorales invasion. These remarkable mechanisms might explain the high incidence of mucormycosis in COVID-19 patients with diabetes and, therefore, suggest regulation of GRP78 expression, management of glycemia and glucocorticoid treatment as potential therapeutic targets of this severe coinfection.
The COVID-19 has impacted many nations across the world, disrupting lives, economies and societies. The Post covid complications are much worse. Now a spike of black fungus is being observed among individuals hospitalized for or recovering from COVID19 infection. Black Fungus can even be life-threatening and fatal if not diagnosed and treated in its initial stages. Deep Learning has been revolutionizing in the Health sector and has path-breaking applications. The proposed research study aims at anticipating black fungus in covid affected patients majorly through deep learning. The Dataset used in this study has attributes related to covid19, the presence of any comorbidities like cancer or diabetes, medical treatment given to patient for covid, and the location of mucormycosis in the body. Popular deep learning methods such as RNN, CNN and ANN were used in this research. SVM (Support Vector Machine) which is also an efficient supervised Machine Learning Algorithm has also been used. The RNN (Recurrent Neural Networks) algorithm showed superior accuracy in predicting black fungus comparatively over other algorithms. This study provides a wide overview of the relative performance of different deep learning algorithms for black fungus prediction. Based on the covid treatment taken by the patient and his comorbidities, this study can help doctors by predicting patients who are more vulnerable to get infected by black fungus. Such Patients can be kept under supervision and special care can be taken. This relative performance of algorithms is often used to assist researchers in the selection of an appropriate deep learning algorithm for their studies.
The immunocompromised patients who have uncontrolled diabetes, transplants, or long-term corticosteroid therapy are the ones who contract Mucormycosis the most frequently, but it can also affect those who have been injured, have pathology, or use injectable drugs. The study summarizes the consequences, diagnosis, and prevention of Mucormycosis in COVID-19-positive hospitalized diabetic patients, as well as the ramifications of the pandemic. Only occurrences or case series reports with appropriate information regarding risk factors, clinical presentation, course, diagnosis, therapy, and prognosis were included in this research because it was conducted using material found on PubMed. We identified eight patients with pulmonary Mucormycosis and six patients with rhino-orbital-cerebral disease. Despite the fact that 10 (71%) of the patients were males with a median age of 58.5 years (IQR 38-79) and 29% of them were females with a median age of 46.5 years, 8 (8/14, or 57% of the patients) had risk indicators for severe COVID-19 (IQR 32-61). Co-infection is prevented and controlled by using a sterile mask, avoiding touching of the nose, eye mouth, control over steroid medication, and controlling diabetes and other conditions in an exceedingly regulated manner.
COVID-19–associated rhino-orbital cerebral mucormycosis (ROCM) has a rapidly evolving course with high morbidity and mortality. We describe imaging features of COVID-19–associated ROCM based on noncontrast computed tomography (NCCT). This retrospective single-center observational study included 50 patients with COVID-19 from January 1, 2021 to June 30, 2021 who subsequently developed ROCM confirmed by fungal culture studies. All patients underwent NCCT of the paranasal sinuses as the diagnostic workup. The involvement of the nasal cavity, paranasal sinuses, orbits, and intracranial cavity was identified and graded. The ethmoid sinuses were most commonly involved [right ( n = 46 of 50) > left ( n = 45 of 50)], followed by the maxillary, sphenoid, and frontal sinuses. Thinning and erosions of the hard palate were noted in 18% of patients ( n = 9), whereas 34% ( n = 17) showed dehiscence of the lamina papyracea. Retromaxillary fat stranding was noted in 68% of patients ( n = 34). Severe ethmoid sinusitis was associated significantly with ipsilateral pterygopalatine fossa involvement. The extraocular muscles were involved in 64% of patients ( n = 32), with 84% ( n = 42) showing orbital fat stranding. Proptosis of the affected eye was seen in 66% of patients, optic nerve involvement in 52%, and irregularity of globe contour in 12% ( n = 6). The cavernous sinuses were affected in 10% of patients ( n = 5), with three of them having temporal infarcts. COVID-19–associated ROCM is an acute, invasive fungal disease characterized by multisinus involvement, often with orbital and intracranial extension. Bilateral involvement with rapid progression should alert one to underlying COVID-19 disease.
Aim: Acute invasive fungal rhinosinusitis (AIFRS) is a rare infection of the nose and paranasal sinuses that can be fatal. Infection may lead to tissue infarction, necrosis, and thrombosis and rapidly spread intracranially. The aim of this study is to highlight the increasing cases of AIFRS after covid-19 and to investigate the parameters affecting mortality. Material and Method: Total 11 patients diagnosed with AIFRS after COVID-19 were included in this study. Patient age, gender, comorbid diseases, initial symptoms, time between COVID-19 diagnosis and AIFRS diagnosis, intensive care hospitalization history, medical treatments, surgical findings, antifungal treatment, fungal species grown in culture, mortality, and the relationships of these parameters with mortality were also evaluated. Results: A total of 11 patients diagnosed with AIFRS after COVID-19 were included in the study. Among these patients, 81.8% were male, 18. 2% were female, and ages ranged from 57 years to 89 years. The mean time between COVID-19 infection and development of IFRS in patients was 26.09±18.04 days. The initial symptoms in 45.45% of the patients were unilateral periorbital edema, vision loss, and total ophthalmoplegia. The surgical approach was purely endoscopic in all patients. In our study, the mortality rate was 72.7% in COVID-19 related AIFRS patients. Conclusion: As a result, in our study, we found an increase in AIFRS incidence and mortality due to the systemic effects of COVID 19 and the treatments used for it. AIFRS should be suspected when a patient presents acute sinusitis symptoms after COVID-19 infection.
Objective: The aim of this review literature is to collate and analyse various case reports and series reporting mucormycosis in COVID and post-COVID patients in India and worldwide. Methods: A systematic literature search was conducted from December 2019 to June 2021 using keywords. Details of all the case reports/ series that reported rhino-orbital-cerebral mucormycosis in COVID and post-COVID settings were retrieved and analysed. Results: In this systematic review, 33 articles were included and a total of 181 cases of mucormycosis in COVID and post-COVID patients were reported. Mucormycosis was predominantly seen in males (71.2%) as compared to females (28.7%). History of steroid use was present in 113 patients (62.4%). Type 2 diabetes mellitus was the most common independent risk factor, present in 138 patients (76%). Sino-nasal involvement was seen in 27 patients (14.9%), rhino-orbital involvement in 114 patients (62.9%), andrhino-orbital-cerebral involvement was observed in 40 patients (22%). Improvement in clinical status was observed in 106 patients (58.5%) while 38 patients (21%) expired. Conclusions: A rapid rise in cases of mucormycosis had been reported in the COVID era. Unwarranted use of steroids coupled with uncontrolled hyperglycemia, unregulated activation of inflammatory mediators and overactivation of entry-point receptors inflicted by the Coronavirus cause a state of immune dysregulation, leading to opportunistic invasive fungal infections. A delay in diagnosis can result in disfigurement, functional loss, or even death. Multidisciplinary management with prompt reversal of risk factors is recommended.
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.
During the second wave of coronavirus disease, or COVID-19, infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in the year 2021 around the globe, there is a surge in the number of cases of mucormycosis or “Black Fungus” that is directly/indirectly associated with COVID-19.
In this review article, mucormycosis of the orofacial region has gained importance from the maximum published literature (45 articles) from various databases like PubMed, Google Scholar, Scopus, Web of Science, and Embase.
Rhino-orbital cerebral mucormycosis (ROCM) is a fatal condition associated with COVID-19 among categories of mucormycosis such as pulmonary, oral, gastrointestinal, cutaneous, and disseminated. ROCM targets the maxillary sinus, also involving teeth of the maxilla, orbits, and ethmoidal sinus. These are of particular interest to dentists and oral pathologists for proper diagnosis and identification. Co-morbid conditions, especially diabetes mellitus type II, have to be monitored carefully in COVID-19 patients as they have a higher risk of developing mucormycosis. In this review article, various presentations of COVID-19-linked mucormycosis are mentioned having particular emphasis on pathogenesis, signs and symptoms, clinical presentation, various diagnostic modalities including histopathology, radiology like CT and MRI, serology, tissue culture, various laboratory investigations, treatment protocols, management with prognosis, and so on. Any suspected case of mucormycosis needs quick detection and treatment since it progresses quickly due to the destructive course of infection.
Long-term follow-up along with proper care is a must to detect any kind of recurrence.
Introduction and objectives:
Although the ophthalmic manifestations appear to be associated with the coronavirus disease 2019 (COVID-19), there is not enough evidence. Hence, the aim of this study was to determine the various types and frequency of ophthalmic manifestations in patients recovered from SARS-CoV-2 infection in Mexico.
Material and methods:
This retrospective, observational and descriptive study included all patients recovered from SARS-CoV-2 infection attending the tertiary level hospital of Mexican Social Security Institute (IMSS) from June 2020 to June 2022. During the hospital admission of patients, the demographic data such age, name, gender was recorded. Ophthalmologic examination was performed under torchlight by an ophthalmologist in the Department of Ophthalmology from IMSS. Data was compiled and statistically analyzed using Fisher's exact test and Spearman correlation.
Results:
A total of 3,081 SARS-CoV-2-positive patients were recorded, of which 318 (10.32%) met the inclusion criteria. Of them, 21 (6.60%) had ophthalmic manifestations and the female-to-male ratio was 1.6:1. The mean age (±SD) was 47.95 ± 15.27 years and the median (interquartile range) time from the diagnosis of COVID-19, as defined by positive SARS-CoV-2 RT-PCR testing, to detection of the ophthalmic manifestation was 31 (142) days. The most common ocular manifestation was orbital mucormycosis (23.80%). Interestingly, the presence of ophthalmic manifestations was not associated with severe COVID-19 (p = 0.665).
Conclusions:
The ophthalmic manifestations are infrequent in patients recovered from severe COVID-19. Nevertheless, further large sample studies are needed to confirm these findings.
i>Background: Coronavirus disease 2019 (COVID-19) is associated with diffuse lung damage. Corticosteroids may modulate inflammation-mediated lung injury, reducing progression to respiratory failure and death.
Methods: The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs. usual care alone. The primary outcome was 28-day mortality.
Results: 2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care. Overall, 482 (22.9%) patients allocated dexamethasone and 1110 (25.7%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.75 to 0.93; P<0.001). The absolute mortality rate reductions varied depending on level of respiratory support at randomization: Dexamethasone reduced deaths in patients receiving invasive mechanical ventilation (29.3% vs. 41.4%, RR 0.64 [95% CI 0.51 to 0.81]), in patients receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%, RR 0.82 [95% CI 0.72 to 0.94]), but did not reduce mortality in patients not receiving respiratory support at randomization (17.8% vs. 14.0%, RR 1.19 [95% CI 0.91 to 1.55]).
Conclusions: In patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support.
(Funded by the Medical Research Council and National Institute for Health Research; ClinicalTrials.gov NCT04381936 and ISRCTN 50189673)
Background
Individuals with diabetes are at a greater risk of hospitalization and mortality resulting from viral, bacterial and fungal infections. The Coronavirus Disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread quickly to more than 213 countries across the world and has claimed 395,779 lives as of June 7, 2020. Notably, in several studies, diabetes is one of the most reported comorbidities in patients with severe COVID-19.
Scope of Review
In this review, I will summarize the clinical data on the risk for infectious diseases in individuals with diabetes, highlighting the mechanisms for altered immune regulation. A special focus will be given to coronaviruses. In the light of the new clinical data obtained from COVID-19 patients, mechanisms such as cytokine storm, pulmonary and endothelial dysfunction, hypercoagulation that may render individuals with diabetes more vulnerable to COVID-19 will be discussed in the end.
Major Conclusions
Epidemiological studies show that poorly controlled diabetes is a risk factor for various infectious diseases. Given the global burden of diabetes and pandemic nature of coronaviruses, understanding how diabetes affects COVID-19 severity is critical to design tailored treatments and clinical management of individuals affected by diabetes.
Like severe influenza, coronavirus disease-19 (COVID-19) resulting in acute respiratory distress syndrome (ARDS) has emerged as an important disease that predisposes patients to secondary pulmonary aspergillosis, with 35 cases of COVID-19 associated pulmonary aspergillosis (CAPA) published until June 2020. The release of danger-associated molecular patterns during severe COVID-19 results in both pulmonary epithelial damage and inflammatory disease, which are predisposing risk factors for pulmonary aspergillosis. Moreover, collateral effects of host recognition pathways required for the activation of antiviral immunity may, paradoxically, contribute to a highly permissive inflammatory environment that favors fungal pathogenesis. Diagnosis of CAPA remains challenging, mainly because bronchoalveolar lavage fluid galactomannan testing and culture, which represent the most sensitive diagnostic tests for aspergillosis in the ICU, are hindered by the fact that bronchoscopies are rarely performed in COVID-19 patients due to the risk of disease transmission. Similarly, autopsies are rarely performed, which may result in an underestimation of the prevalence of CAPA. Finally, the treatment of CAPA is complicated by drug–drug interactions associated with broad spectrum azoles, renal tropism and damage caused by SARS-CoV-2, which may challenge the use of liposomal amphotericin B, as well as the emergence of azole-resistance. This clinical reality creates an urgency for new antifungal drugs currently in advanced clinical development with more promising pharmacokinetic and pharmacodynamic profiles.
In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pathologists can be exposed to infection handling surgical specimens. Guidelines related to safety procedures in the laboratory have been released. However, there is a lack of studies performed on biopsy and surgical resection specimens. Here we report the detection of SARS-CoV-2 in formalin-fixed paraffin-embedded samples from surgical resection of tongue squamous cell carcinoma of a patient who developed COVID-19 postsurgery. RNA of SARS-CoV-2 strain was detected in the tumour and the normal submandibular gland samples using real-time PCR-based assay. No viral RNA was found in metastatic and reactive lymph nodes. We demonstrated that SARS-CoV-2 RNA can be detected in routine histopathological samples even before COVID-19 disease development. These findings may give important information on the possible sites of infection or virus reservoir, and highlight the necessity of proper handling and fixation before sample processing.
Significance
In patients with coronavirus disease 2019, a large number of T lymphocytes and mononuclear macrophages are activated, producing cytokines such as interleukin-6 (IL-6), which bind to the IL-6 receptor on the target cells, causing the cytokine storm and severe inflammatory responses in lungs and other tissues and organs. Tocilizumab, as a recombinant humanized anti-human IL-6 receptor monoclonal antibody, can bind to the IL-6 receptor with high affinity, thus preventing IL-6 itself from binding to its receptor, rendering it incapable of immune damage to target cells, and alleviating the inflammatory responses.
Fungal infections are a subset of infectious processes that an otolaryngologist is required to be familiar with. They can be encountered in otology, rhinology and head and neck surgery. The presence of fungal rhinosinusitis is well recognised by otolaryngologists, but the classifications and appropriate management are not so well understood. The prevalence of fungal sinus disease is thought to be have been increasing in recent decades There is speculation that this may be due to increased awareness, antibiotic overuse and increased use of immunosuppressant medications. Added to this, there has been a large amount published on the role of fungi as a causative organism in chronic rhinosinusitis. Given the importance of fungal rhinosinusitis in clinical practice, we aim to review the classification and current management strategies based on up-to-date literature.
Zygomycete infections can be devastating in immunocompromised hosts. Difficulties in the histopathologic differentiation of
this class from other filamentous fungi (e.g., Aspergillus spp., Fusarium spp.) may lead to delays in diagnosis and initiation of appropriate treatment, thereby significantly affecting patient outcome.
A real-time PCR assay was developed to detect species of the zygomycete genera Absidia, Apophysomyces, Cunninghamella, Mucor, Rhizopus, and Saksenaea in culture and tissue samples. Primers and fluorescence resonance energy transfer hybridization probes were designed to detect
a 167-bp conserved region of the multicopy zygomycete cytochrome b gene. A plasmid containing target sequence from Mucor racemosus was constructed as a positive control. The analytical sensitivity of the assay is 10 targets/μl, and a specificity panel
consisting of other filamentous fungi, yeasts (Candida spp.), and bacteria demonstrated no cross-reactivity in the assay. The clinical sensitivity and specificity of the assay
from culture isolates were 100% (39/39) and 92% (59/64), respectively. Sensitivity and specificity determined using a limited
number of fresh tissue specimens were both 100% (2/2). The sensitivity seen with formalin-fixed, paraffin-embedded tissues
was 56% (35/62), and the specificity was 100% (19/19). The speed, sensitivity, and specificity of the PCR assay indicate that
it is useful for the rapid and accurate detection of zygomycetes.
Adult respiratory distress syndrome (ARDS) is the leading cause of death associated with SARS-CoV-2 infection and COVID-19. IGF-1 has been implicated in ARDS, yet its role in relation to COVID-19-related lung injury has not been investigated. We hypothesize that blockage of the IGF-1 receptor (IGF-1R) mitigates lung injury and decreases the risk of death in patients COVID-19-related ARDS. Patients with fibroproliferative ARDS have been shown to have increased IGF-1 and IGF-1R staining in lung tissue specimens. Rising levels of IGF-1 in bronchioalveolar fluid (BAL) and increased IGF-1 mRNA expression in lung tissues (but declining serum IGF-1 levels) have been found in late stage ARDS compared with early lung injury. Blockage of IGF-1R decreases lung tissue damage and increases survival in bleomycin-induced as well as H1N1 influenza-related lung injury animal models. Teprotumumab is a monoclonal antibody directed against the IGF-1R that was FDA-approved in 2020 for the treatment of Graves’ orbitopathy. In order to determine if teprotumumab may reduce lung injury and death related to ARDS in the setting of COVID-19, preliminary clinical data is needed. IGF-1 levels in serum and BAL fluid must be measured in patients with COVID-19-related ARDS. Histopathology from lung samples from patients with COVID-19-related ARDS must be examined for increased expression of the IGF-1R. Once these are ascertained, and if the data support IGF-1 involvement, a randomized, placebo-controlled phase 2A trial of teprotumumab therapy in the setting of COVID-19-related ARDS and non-COVID-19-related ARDS designed to generate initial data on short-term efficacy, safety, dosing and administration should be performed.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been sweeping across the globe. Based on a retrospective analysis of SARS and influenza data from China and worldwide, we surmise that the fungal co-infections associated with global COVID-19 might be missed or misdiagnosed. Although there are few publications, COVID-19 patients, especially severely ill or immunocompromised, have a higher probability of suffering from invasive mycoses. Aspergillus and Candida infections in COVID-19 patients will require early detection by a comprehensive diagnostic intervention (histopathology, direct microscopic examination, culture, (1,3)-β-D-glucan, galactomannan, and PCR-based assays) to ensure effective treatments. We suggest it is prudent to assess the risk factors, the types of invasive mycosis, the strengths and limitations of diagnostic methods, clinical settings, and the need for standard or individualized treatment in COVID-19 patients. We provide a clinical flow diagram to assist the clinicians and laboratory experts in the management of aspergillosis, candidiasis, mucormycosis, or cryptococcosis as co-morbidities in COVID-19 patients.
We review two cases of adolescents with orbital cellulitis, sinusitis and SARS- CoV-2 infection presenting to emergency departments within a 24 hour period. SARS-CoV-2 samples obtained within 24 hours were positive, supporting prior infection despite relatively limited early symptoms of COVID-19. Unusual clinical and radiographic characteristics included hemorrhagic abscess with blood of varying age in the first, intracranial epidural abscess in the second, radiographic signal consistent with hemorrhagic or thrombotic phenomena, retro-maxillary antral fat changes, and meningeal enhancement or extension in both cases. Radiographic findings thereby mimic fungal infection, although final cultures and ancillary investigation for allergic and invasive fungal disease have remained negative. These cases highlight two unusual orbital presentations of cellulitis occurring in the context of SARS-CoV-2 co-infection.
The 2019 Coronavirus epidemic, provisionally called 2019-nCoV, was first identified in Wuhan, China, in persons exposed to a seafood or wet market. There is an international push to contain the virus and prevent its spread. It is feasible that potentially infectious samples may be received in histopathology laboratories for diagnosis. This technical note presents disinfection procedures and histotechnology processes that should alleviate the risk of infection to laboratory staff. Using data obtained from similar coronaviruses, e.g. severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), experts are confident that 70% ethanol and 0.1% sodium hypochlorite should inactivate the virus. Formalin fixation and heating samples to 56oC, as used in routine tissue processing, were found to inactivate several coronaviruses and it is believed that 2019-nCoV would be similarly affected.
Available Open Access on:
https://www.tandfonline.com/doi/full/10.1080/01478885.2020.1734718?src=
PURPOSE: Invasive fungal sinusitis is a rare but potentially lethal disease that primarily affects immunocompromised patients. The purpose of this study was to review an academic medical center's experience in the presentation, diagnosis, and treatment of invasive fungal sinusitis.
METHODS: A retrospective chart review was performed at a single institution over a 17-year period. Medical records, radiographic imaging, and operative reports were analyzed. Bivariate and multivariable analyses were performed to determine factors that affected visual acuity outcomes and mortality.
RESULTS: Fifty-five patients with histopathologically confirmed invasive fungal sinusitis were included. The average duration of follow up was 1.8 ± 2.6 years (range: 1 week to 10 years). The most common causes of immunosuppression were hematologic malignancy (45%), diabetes (31%), and organ transplantation (9%). At presentation, 35% of individuals were neutropenic (absolute neutrophil count < 500/μl). All patients received systemic antifungal treatment. A surgical intervention was performed on 50 patients (91%), and all but one had functional endoscopic sinus surgery. Nine (16%) patients underwent orbital exenteration. Multivariable analysis of visual acuity outcomes demonstrated that individuals infected with Zygomycota had 6-7 lines worse vision than those infected with Ascomycota (mean difference in logMAR 0.66, 95% confidence interval 0.27 to 1.06, p = 0.001). Patients who had functional endoscopic sinus surgery had 7-8 lines better visual acuity than those without functional endoscopic sinus surgery (mean difference in logMAR -0.76, 95% confidence interval -1.13 to -0.38, p < 0.001). The overall death rate due to infection was 24%. Bivariate models demonstrated no difference in mortality in patients receiving exenteration versus those who did not (p = 0.14). Multivariable analysis of mortality demonstrated that neutropenia increased mortality (adjusted odds ratio 10.05, 95% confidence interval 1.49 to 67.67, p = 0.02). Having a greater number of surgeries was associated with an increased rate of survival (adjusted odds ratio 0.39, 95% confidence interval 0.15 to 0.96, p = 0.04).
CONCLUSIONS: Invasive fungal sinusitis is an aggressive disease with significant mortality. Patients with neutropenia had a lower rate of survival, and infection with Zygomycota was associated with worse visual acuity outcomes. Those having functional endoscopic sinus surgery had better final visual acuity, and an increased number of surgeries was associated with a decreased chance of death. Exenteration yielded no observed survival benefit.
Aim
To report the frequency and factors affecting patients’, globe and vision survivals in rhino-orbito-cerebral mucormycosis (ROCM).
Methods
This is a retrospective study of 63 patients (79 eyes) with biopsy-proven ROCM at a university hospital 2008–2016. Systemic and ophthalmic manifestations, imaging, management and final outcomes were recorded. Globe survival was defined as no exenteration and vision survival as final visual acuity of light perception and more.
Results
Mean age was 55.5 (SD 12.9) years with no gender preference. Diabetes was the most common underlying disease (68.3%). Patient survival was observed in 57.1 % (36/63). Presence of frozen eye (OR 4.6), nasal mucosal involvement (OR 7.3) and shorter duration of antifungal therapy (OR 1.03) were significantly associated with lower patient survival. Exenteration did not significantly change the survival. Globe survival was detected in 43% (34/79). Higher white blood cell (WBC) count was associated with a lower globe survival (p=0.02). Vision survival was observed in 25.3% (20/79) in whom younger age was significantly associated with a worse vision survival.
Conclusion
Patient, globe and vision survivals were 57%, 43% and 25%, respectively. Exenteration did not affect the patients’ survival. While frozen eye and nasal mucosal involvement were significantly associated with a lower survival, higher WBC count significantly increased the risk of exenteration.
The diagnosis and treatment of mucormycosis are challenging. The incidence of the disease seems to be increasing. Hematological malignancies are the most common underlying disease in countries with high income and uncontrolled diabetes in developing countries. Clinical approach to diagnosis lacks sensitivity and specificity. Radiologically, multiple (≥10) nodules and pleural effusion are reportedly associated with pulmonary mucormycosis. Another finding on computerized tomography (CT) scan, which seems to indicate the presence of mucormycosis, is the reverse halo sign. Microscopy (direct and on histopathology) and culture are the cornerstones of diagnosis. Molecular assays can be used either for detection or identification of mucormycetes, and they can be recommended as valuable add-on tools that complement conventional diagnostic procedures. Successful management of mucormycosis is based on a multimodal approach, including reversal or discontinuation of underlying predisposing factors, early administration of active antifungal agents at optimal doses, complete removal of all infected tissues, and use of various adjunctive therapies. Our armamentarium of antifungals is slightly enriched by the addition of two newer azoles (posaconazole and isavuconazole) to liposomal amphotericin B, which remains the drug of choice for the initial antifungal treatment, according to the recently published guidelines by ECIL-6, as well as those published by ECMM/ESCMID. Despite the efforts for better understanding of the pathogenesis, early diagnosis and aggressive treatment of mucormycosis, the mortality rate of the disease remains high.
Objective
The aims of the present study were to evaluate the clinical significance of the delay for surgical treatment and the prognostic value of other clinical, pathologic, and microbiological variables among hematologic patients affected by acute invasive fungal rhinosinusitis (AIFRS). Furthermore, we propose our early diagnosis and treatment protocol, reporting its 10-year results.
Study Design
Monocentric retrospective analysis.
Setting
The study was conducted from 2001 to 2017 at the University Hospital of Bologna, Italy.
Subjects and Methods
The impact of time to treatment and clinical, pathologic, and microbiological variables were analyzed among patients with histologically and microbiologically proven AIFRS. The outcomes of patients treated before the introduction of the early diagnosis protocol were compared with those treated afterward.
Results
Nineteen patients affected by AIFRS were eligible for the study. Treatment delay >4 days ( P = .002), infection caused by Mucorales ( P = .015), and extension of the disease were negative prognostic variables ( P = .017). The application of our protocol significantly reduced the delay for diagnosis and appropriate treatment by an average of 7.3 days ( P = .02).
Conclusion
The promptness of the diagnosis and surgical treatment may play a significant role in the management of AIFRS, as it appears to be significantly associated with the disease outcome. Our protocol may help to reduce the time required for diagnosis of high-risk hematologic patients.
Invasive sino-orbital fungal infections are life-threatening complications of immunonosupression that are difficult to treat. Currently there are no standard treatment guidelines. The most widely accepted therapy includes parenteral anti-fungal therapy and surgical debridement of sinuses with orbital exenteration, a procedure that is not only disfiguring, but may increase morbidity. Injection of retrobulbar Liposomal Amphotericin B (L-AMB) is an alternative approach that provides local administration to infected tissues. The adjunct use of anti-fungal retrobulbar injections not been extensively reviewed in treating sino-orbital infection. We are reporting the multimodal approach of using L-AMB retrobulbar injections in combination with sinus debridement, intravenous (IV) anti-fungal therapy, and hyperbaric oxygen (HBO) for the management of sino-orbital infection.
Review of literature of 12 cases and retrospective evaluation of one patient with sino-orbital Aspergillus flavus infection on chemotherapy for T-cell acute lymphocytic leukemia treated with retrobulbar Amphotericin B, IV anti-fungal agents, and hyperbaric oxygen therapy. Clinical characteristics, radiographic features, management techniques, and clinical outcomes are described.
Retrobulbar Amphotericin B injection may be an effective adjunct to hyperbaric oxygen and parenteral anti-fungals in the control of sino-orbital fungal infections.
Mucormycosis is a rare and often fatal opportunistic angioinvasive infection seen mostly in immunocompromised patients, such as those with diabetes mellitus, cancer, or renal failure. Ophthalmic manifestations of orbital mucormycosis include ocular pain, periocular oedema, visual loss, ophthalmoplegia, proptosis, and ptosis. Although therapy for orbital mucormycosis consists of maximally tolerated doses of antifungal agents (e.g., amphotericin B) and extensive surgical debridement, treatment remains ineffective in up to 20% of cases. We describe two patients with rhino-orbitalmucormycosis who were successfully treated with posaconazole in conjunction with intravenous (IV) amphotericin B and sinus surgical debridement. These cases highlight several unusual early manifestations of orbital mucormycosis, including disc oedema and amaurosis fugax, as well as the applicability of a new extended-spectrum antifungal agent in management of orbital zygomycosis.
Acute invasive fungal sinusitis (AIFS) is an aggressive and often fatal infection. Despite improvements in medical and surgical therapy, survival remains limited and the factors that contribute to patient outcomes remain poorly understood. The current study systematically reviews and quantitatively synthesizes the published literature to characterize prognostic factors associated with survival.
Systematic review.
Fifty-two studies comprising a total of 807 patients met inclusion criteria and were used for analysis of treatment, presentation, and outcomes. Univariate and multivariate logistic regression was used to identify prognostic factors.
All studies were classified as level 4 evidence, as per definitions provided by the Oxford Center for Evidence-Based Medicine. The most common presenting symptoms of patients with AIFS were facial swelling (64.5%), fever (62.9%), and nasal congestion (52.2%). Most patients were treated with a combination of intravenous antifungal medication and surgery. The overall survival rate was 49.7%. On univariate analysis, poor prognosis was associated with renal/liver failure, altered mental status, and intracranial extension. Patients who were diabetic, had surgery, or received liposomal amphotericin B had an improved chance of survival. On multivariate analysis, advanced age and intracranial involvement were identified as independent negative prognostic factors. Positive prognostic factors again included diabetes and surgical resection.
The overall mortality of patients with AIFS remains high, with only half of the patients surviving. Diabetic patients appear to have a better overall survival than patients with other comorbidities. Patients who have intracranial involvement, or who do not receive surgery as part of their therapy, have a poor prognosis.
N/A.
A 61-year-old male underwent a cardiac transplant for congenital dilated cardiomyopathy. Two months post-transplantation, after a complicated clinical course, he was noted to have progressive proptosis and limitation of motility OD. Computed tomography showed opacification of the right maxillary sinus with the suggestion of a fungus ball and soft tissue infiltration along the floor of the orbit adjacent to the inferior rectus, extending posteriorly to within millimeters of the superior and inferior orbital fissures. An orbital biopsy demonstrated the presence of fungal hyphae and A. fumigatus was cultured. The patient was treated with systemic antifungal therapy and intralesional retrobulbar amphotericin B (without debridement) with successful eradication of the fungal pathogen. Intralesional amphotericin in combination with systemic antifungal therapy without limited debridement is rarely reported and may be an alternative to limited debridement or exenteration in orbital aspergillosis.
To determine radiographic findings on computed tomography (CT) and magnetic resonance imaging (MRI) predictive of acute fulminant invasive fungal sinusitis (AFIFS) in an immunocompromised patient population.
Retrospective case-control study.
Tertiary referral hospital.
Cases were 17 immunocompromised patients with confirmed AFIFS after surgical debridement or biopsy. Controls were 6 immunocompromised patients histopathologically negative for AFIFS after surgical debridement or biopsy.
Computed tomographic and MRI scans were independently reviewed by 2 neuroradiologists to identify imaging characteristics predictive of AFIFS. Operative reports and histopathologic, microbiologic, and survival data were reviewed.
No significant differences with regard to baseline characteristics between the 2 groups were identified. There was moderate or substantial agreement (κ = 0.40-0.77) between the 2 radiologists for all imaging parameters except MRI loss of contrast enhancement (κ = 0.16). Magnetic resonance imaging was more sensitive than CT for the diagnosis of AFIFS (sensitivity 85% and 86% for both reviewers compared with 57% and 69%). Extrasinus invasion with MRI was the most sensitive individual parameter (87% and 100%). Magnetic resonance imaging and CT had similar specificities, and perisinus invasion was the most specific individual parameter (83% and 83% for MRI compared with 81% and 83% for CT). The positive predictive values were high for both imaging modalities (93% and 94% for MRI compared with 89% and 93% for CT). The negative predictive values were lower for both modalities and varied more between reviewers (71% and 100% for MRI compared with 45% and 67% for CT).
Magnetic resonance imaging is more sensitive for detecting early changes of AFIFS than CT. Both imaging modalities have similar specificities. Perisinus invasion with MRI was the most sensitive and specific single parameter evaluated.
Dexamethasone in hospitalized patients with COVID-19 -preliminary report
- P Horby
- W S Lim
- J R Emberson
Horby P, Lim WS, Emberson JR, et al; RECOVERY Collaborative
Group. Dexamethasone in hospitalized patients with COVID-19 -preliminary report. N Engl J Med. 2020 Jul 17:NEJMoa2021436.
Dexamethasone in hospitalized patients with COVID-19 - preliminary report.
- Horby