Risk factors affecting outcome of rhino-orbital-cerebral mucormycosis in COVID-19 patients

Background: Mucormycosis is a serious life-threatening fungal infection that recently made severe sudden and devastating surge during the second wave of the COVID-19 epidemic with a mortality rate of up to 50%. Although the causality link between COVID-19 and rhino-orbito-cerebral mucormycosis (ROCM) remains unclear, many factors including poor diabetes control, high doses of steroids, viral-induced lymphopenia, and cytokine storm have been attributed to ROCM in patients with COVID-19. Orienting to risk factors and early recognition of this potentially fatal opportunistic infection is the key to optimal management and improved outcomes. In these contexts, we conducted a prospective study for 33 patients admitted to our tertiary hospital to determine the risk factors for ROCM in patients with COVID-19 and the cumulative mortality rates. Result(s): This study found a statistically significant relation between the fate of death in COVID-MUCOR patients who had presented fever, ophthalmoplegia, facial skin necrosis, and visual loss with those who received dose of steroid to control their respiratory symptoms P < 0.001. Death from COVID-MUCOR was statistically significant related to the prolonged interval from the onset of the symptoms to start of treatment and intervention. Also, it was found that there was a significant decrease in duration between COVID-19 infection and the start of mucormycosis (days) with incidence of DKA on admission. Nineteen (57.6%) of the patients had uncontrolled diabetes mellitus (hemoglobin A1C (HbA1c) of > 7.0%). Conclusion(s): Mucormycosis epidemic was precipitated by a unique confluence of risk factors: diabetes mellitus, widespread use of steroids, and perhaps SARS-CoV-2 infection itself. Restricting steroid use in patients with severe COVID-19 requiring oxygen therapy, and screening for and optimally controlling hyperglycemia, can prevent COVID-MUCOR in a large majority.Copyright © 2023, The Author(s).

COVID-associated rhinocerebral mucormycosis: a retrospective analysis of presentation and outcomes.

OBJECTIVES: To comprehensively analyse the disease presentation and mortality of COVID-associated rhino-orbito-cerebral mucormycosis. METHODS: A retrospective analysis of the demographics, clinical and radiographic findings was performed. A binary logistic regression analysis was performed to examine the survival of patients with mucormycosis from hypothesised predictors. RESULTS: A total of 202 patients were included in this study. Statistical significance was demonstrated in the predilection to the male gender, recent history of SARS-COV-2, history of use of corticosteroid and hyperglycemia in this cohort of CAM. The mortality rate was 18.31%. Advanced age, raised HbA1c and intra-orbital extension were found to be predictors adversely affecting survival. CONCLUSION: Early diagnosis, aggressive surgical therapy, early and appropriate medical therapy can help improve outcomes. LEVEL OF EVIDENCE: Level 4.

Association of Risk Factors among Nasal and Orbital Mucormycosis in Coronavirus Disease 2019 Infection: A Cross-Sectional Study.

Purpose: To study the risk factors of mucormycosis and analyze their association among nasal and orbital mucormycosis in Coronavirus disease 2019 (COVID-19) infection. Methods: All patients diagnosed of rhino-orbito-cerebral mucormycosis (ROCM) with previous COVID-19 infection were included in the study. The details such as age, sex, presence of co-morbidities, and serum ferritin levels were collected. ROCM patients were classified into two groups, nasal mucormycosis (stage 1 and 2 of ROCM) and orbital mucormycosis (stage 3 and 4 of ROCM), and data were collected. Duration of COVID-19 symptoms, the time interval between COVID-19 infection and onset of ROCM symptoms, computed tomography severity score (CTSS) and usage of steroids were collected accordingly. The collected data were compared between nasal group and orbital group. Results: Among 52 patients, 15 patients had nasal and 37 patients had orbital mucormycosis. Forty-one patients were more than 40 years, 43 patients were males. Seven out of ten risk factors were found to be significant on comparing nasal and orbital group. Patients of age more than 40 years (P = 0.034), elderly diabetics (P = 0.014), poor control of diabetes (P = 0.003), high serum ferritin levels (P = 0.043), duration between COVID-19 and mucormycosis of more than 20 days (P = 0.038), CTSS of more than 9/25 (P = 0.020), and steroid usage during COVID-19 infection (P = 0.034) are prone to develop orbital mucormycosis. On multivariate logistic regression analysis, these variables did not emerge as independent risk factors. Conclusions: Patients with severe COVID-19 infection along with other associated risk factors can be prone to develop severe forms of mucormycosis. We did not find them to be statistically significant on multivariate analysis. In the future, large scale studies are needed to know their significance.

COVID-19-associated mucormycosis in India: Why such an outbreak?

An unprecedented mucormycosis outbreak occurred in India during the second COVID-19 wave in spring 2021. COVID-19-associated mucormycosis (CAM) was observed, mainly rhino-orbito-cerebral mucormycosis (ROCM), in patients with poorly controlled diabetes and treated with inappropriate doses of glucocorticoids. The aim of this mini-review was to compare the characteristics of the CAM epidemic in India with (i) mucormycosis cases before the COVID-19 pandemic and (ii) CAM in the rest of the world (particularly in France) in order to identify the reasons for this outbreak. In India, the major mucormycosis epidemiologic change during the COVID-19 pandemic was an increase in the percentage of patients treated with corticosteroids who developed CAM. Compared with the rest of the world, India reported a higher mucormycosis incidence even before the COVID-19 pandemic. Moreover, in India, patients with CAM were more likely to have diabetes mellitus and ROCM; conversely, mortality rates were lower. The reasons for such a localized epidemic in India have remained unclear, but some hypotheses can be put forward, particularly the combination of high prevalence of uncontrolled diabetes mellitus and frequent indiscriminate corticosteroid utilization in a country that already had a high mucormycosis burden before the COVID-19 pandemic.

Epidemiology of COVID-19-Associated Mucormycosis.

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

Acute Fulminant Mucormycosis Triggered by Covid 19 Infection in a Young Patient.

Covid 19 infection can result in various opportunistic infections. Altered immune response, associated comorbid conditions like diabetes, prolonged steroid and broad spectrum antibiotics usage with ICU interventions lead to increased chance of such superadded infections in covid 19 patients. Here we report a case of 31 year old male with covid 19 infection who had new onset Diabetes Mellitus, developed severe acute fulminant Mucormycosis during the treatment for covid 19 infection. He presented with severe headache, nasal obstruction and discharge, bilateral ophthalmoplegia and blindness with Cavernous Sinus Thrombosis. Patient underwent aggressive surgical debridement with frontal craniectomy, maxillectomy and right orbital evisceration and left endoscopic orbital decompression and judicious efforts to revert back the immunocompromised status with high dose of Liposomal amphotericin. Post operatively patient developed right temporal lobe abscess which was drained through Endonasal Endoscopic Trans Cavernous drainage of Temporal Lobe Abscess. Patient is in 2 months follow up, with bilateral blindness and tolerating oral feeds with improved left eye ophthalmoplegia. It is imperative to note that the rising trend of mucormycosis is there in Covid 19 infections and it should be dealt with high index of suspicion in high risk patients and early aggressive treatment can save the patient as the survival rate is not high in such infections.

Rhino-Orbito-Cerebral Mucormycosis During the Second Wave of Covid-19: The Indian Scenario.

Mucormycosis is a life threatening, opportunistic infection often seen in individuals with a weak immune system. With an upsurge of cases of Covid-19, a drastic increase in cases of Rhino-Orbito-Cerebral Mucormycosis is being witnessed at present. This article has been written with the purpose of understanding the factors responsible for it and the challenges it brings along for the Indian health-care system at present. Possible solutions for dealing with these problems have also been included in the manuscript. Google, PubMed and ENT Cochrane databases were searched without a time limit using key words like "Mucormycosis", "Rhino-cerebral-mucormycosis" in conjunction with "COVID-19" and "SARS CoV-2". We found 34 articles to be relevant and hence included them to write this review. Rhino-Orbito-Cerebral Mucormycosis is being seen due to coming together of the three entities-the agent, host and environment that constitute the epidemiological triad for this disease in India. Responsible factors are uncontrolled diabetes mellitus, overzealous use of steroids and antibiotics and other environment related issues. The solutions for these problems lie in spreading awareness about prevention of these practices along with early diagnosis and treatment of mucormycosis. To deal effectively with this situation, particularly when there is an existing overload on otolaryngologists and the rest of the health-care system, a multipronged and multilevel collaborative approach is the need of the hour. With effective Standard Operating Procedures and guidelines promoting a multidisciplinary approach for early diagnosis and treatment, we can surely overcome this situation.

Rhino-Orbital Cerebral Mucormycosis in a Non-diabetic Patient Following COVID-19 Infection: A Case Report and Literature Review.

Rhino-orbital cerebral mucormycosis has been commonly seen during the coronavirus disease 2019 (COVID-19) pandemic. Several factors responsible for etiology and pathophysiology have been identified, among which corticosteroids and diabetes have contributed to the lion's share of the outbreak of mucormycosis. In this report, we discuss a case of a 41-year-old non-diabetic male with a recent convalescence from COVID-19 infection presented with gradual vision loss and loss of sensations in his right eye. He was found to have periorbital swelling, restriction of extraocular movements in all gazes, chemosis, ptosis of the right eye, and right maxillary sinus tenderness. His serum investigations, radiologic findings, and blood culture were indicative of rhino-orbital cerebral mucormycosis. He was started on systemic liposomal amphotericin B immediately and underwent aggressive surgical debridement. A high index of clinical suspicion, aggressive multifaceted management, and follow-up are needed to have successful outcomes, thereby lowering the morbidity of coronavirus-associated mucormycosis.

Rhino-orbito-cerebral Mucormycosis: Pictorial Review.

Mucormycosis (MCR) is a fulminant, potentially lethal, opportunistic fungal infection. Diabetes, immunocompromised states and elevated serum iron levels are the most important risk factors for contracting MCR infection. Recently, MCR co-infections have been observed in patients with COVID-19 disease owing to a complex interplay of metabolic factors and corticosteroid therapy. Rhino-orbito-cerebral mucormycosis (ROCM) is the most common clinical form of MCR infection and refers to infection of the nasal cavities, paranasal sinuses, neck spaces, orbits and intracranial structures. Sinonasal inoculation is typically the primary site of infection; the necrotising and angioinvasive properties of the fungus facilitate its spread into adjacent structures. In this review, we discuss the pertinent mycology and risk factors of MCR infection. The review also aims to acquaint the reader with the cross-sectional imaging appearances of ROCM and its complications. All the cases discussed in this pictorial essay are microbiologically and/or histopathologically proven cases of ROCM with concomitant COVID-19 infection.

COVID-19 associated rhino-orbito-cerebral mucormycosis, risk factors and outcome predictors; a multicentric study.

BACKGROUND: Since the onset of the Covid-19 pandemic, an increase in mucormycosis cases has been observed in many countries, including Iran. However, the role of covid-19 and associated risk factors have not been thoroughly investigated. OBJECTIVE: This study is designed to identify epidemiologic characteristics, risk factors, and outcome predictors of Covid-19-Associated Rhino-Orbito-Cerebral Mucormycosis (C-ROCM). METHODS: Data of pathology proven Covid Associated ROCM cases were retrospectively obtained from 7 tertiary care centers throughout Iran from February 20, 2021, to July 22, 2021. Univariate and multivariate analyses were performed using binary logistic regression to assess the effects of various factors on the outcome. RESULTS: A total of 132 patients with C-ROCM were included in the study. The mean age of patients was 61.6 ± 13.9 (60.6% male). In 12 patients (9.1%), both eyes were involved. Diabetes was the most common comorbidity (94.7%). The mortality rate was 9.1%, higher in males (12.5%) than females (3.8%). Severe vision impairment was seen in 58 patients (43.9%). Main factors that had a negative impact on the outcome in the univariate analysis include older age (P < 0.001), higher steroid dosage (P < 0.001), higher HbA1c level (P < 0.001), Covid-19 severity (P < 0.001), and brain involvement (P < 0.001). However, in the multivariate analysis, the effects of age (P = 0.062), steroid dosage (P = 0.226), and Covid-19 intensity (P = 0.084) decreased, and the difference was no longer statistically significant. CRAO was a predictor of mortality in the univariate analysis (P = 0.008, OR = 4.50), but in the multivariate analysis, this effect decreased and was no longer significant (P = 0.125). CONCLUSION: The risk of C-ROCM and its complications may increase in patients with more severe Covid-19, steroid over-prescription, ICU admission due to Covid-19, and poor glycemic control during and after Covid-19 treatment.

Otorhinolaryngological presentations of mucormycosis amid COVID-19 pandemic in a tertiary care hospital.

Objective: To describe presentations, comorbidities, investigations, and surgical treatment of patients with mucormycosis amid the COVID-19 pandemic in a tertiary care hospital in Khyber Pakhtunkhwa, Pakistan. Methods: This descriptive study was conducted at the department of ENT, and Head and Neck Surgery, Medical Teaching Institute, Lady Reading Hospital, Peshawar, Pakistan from June 2020 to June 2021. All the patients fulfilling the inclusion criteria were included. Patients with COVID-19 were diagnosed based on real-time polymerase chain reaction (RT-PCR). After diagnosing mucormycosis computed tomography (CT) scan and/or magnetic resonance imaging (MRI) were performed for subsequent surgical clearance. After taking informed consent demographic data were collected on a proforma and analyzed using SPPS version 25. Results: Out of 23 patients males were 14(60.9%), females were 9 (39.1%) with a male: female ratio of 1.5:1. Mean ± SD age was 51.26 ± 1.41 years. Nasal obstruction and headache were the most common (8, 34.8%) presentations. The commonest co-morbidities were hypertension with diabetes mellitus (8, 34.8%). Out of 23 patients, 16(69.6%) had COVID-19 PCR positive. The majority of patients (17, 73.9%) were not vaccinated against COVID-19. Most of the patients (9, 39.1%) had HbA1c levels of 7% to 8.9%. The commonest surgery was endoscopic debridement of paranasal sinuses (9, 39.1%), while the commonest CT scan finding was a heterogeneous lesion involving the nose, maxillary and ethmoid sinuses (12, 52.2%). Conclusion: Mucormycosis of paranasal sinuses with/or without intracranial extension is frequently seen in unvaccinated patients having uncontrolled diabetes and COVID-19 infection.

Various Treatment Modalities in COVID-19 Associated Facial Mucormycosis and the Need for its Surgical Management: A Systematic Review.

Introduction: Mucormycosis emerged as a wildfire in post-covid-19 infected patients. Most frequently involved sites of mucormycosis are rhino-orbital, rhino-sinusal and rhino-orbito-cerebral. The hallmark sign of mucormycosis is tissue necrosis, which is often a late sign. The fatality rate of mucormycosis is 46% globally. Despite early aggressive combined surgical and medical therapy, the prognosis of mucormycosis is poor. Methods: We searched the electronic database of PubMed, web of science, Embase, Scopus and Google Scholar from Jan 2020 until December 2021 using keywords. We retrieved all the granular details of original research articles, case reports/series of patients with rhino-orbito-cerebral mucormycosis (ROCM), and COVID-19 reported worldwide. Subsequently, we analyzed the patient characteristics, associated comorbidities, location of mucormycosis, treatment given and its outcome in people with COVID-19. (Prospero registration-CRD42021256830, June 4, 2021). Results: Overall, 544 rhino-orbito-cerebral mucormycosis patients were included in our review with a history of Covid-19 infection. Out of which 410 patients had diabetes mellitus which has proven to be major contributing immunocompromised disease. Other diseases like hypertension, chronic kidney diseases, hypothyroidism, etc., were also attributed as an immunocompromised disease causing increased number of covid associated mucormycosis cases. We found out that total number of patients alive after taking only antifungal drug treatment were 25 in number, whereas total number of patients alive when antifungal drugs were combined with surgical intervention were 428 which was significantly higher. Conclusion: Our systematic review concluded that surgical debridement should be performed whenever feasible in parallel to antifungal treatment in order to reduce the mortality rate of COVID-19 associated rhino-orbito-cerebral mucormycosis patients.

Mucormycosis: The Scathing Invader.

Mucormycosis is an invasive fungal infection that has been increasing in incidence over the years. Increase in the number of diabetics, malignancy patients, and use of immunosuppressants has mainly led to this gradual upward surge. Mucormycosis has various clinical forms, including rhino-orbito-cerebral, pulmonary, gastrointestinal, and cutaneous. Fungi belonging to Mucorales are thermotolerant and ubiquitous, found growing on organic substrates such as bread, decaying fruits and vegetables, crop debris in soil, compost, and animal excreta. During this second wave of the COVID-19 pandemic, the number of cases of mucormycosis has increased manifold in a short span of time. Associated comorbidity of diabetes mellitus, increased use of higher doses and prolonged duration of systemic corticosteroids, the glucogenic and prothrombotic propensity of the virus, hypoxic environment, COVID pneumonia, increased hospitalization, ICU admissions, and mechanical ventilation have all contributed toward this high rise in numbers. The rhin-orbito-cerebral form is the commonest manifestation of mucormycosis in COVID. Rhizopus oryzae, the main species causing mucormycosis, is identified by hyaline, sparsely-septate, broad, ribbon-like hyphae with irregular right-angle branching ribbon-like hyphae with rhizoids. For the early diagnosis of this infection, 10% KOH mount is very important. These fungi are very rapidly growing and thus can be differentiated from their main ally, Aspergillus. Treatment is mainly in the form of extensive surgical debridement along with liposomal amphotericin B. Posaconazole and isavuconazole are second-line agents, which can also be used for maintenance. Control of diabetes and COVID-19, along with judicious use of antibiotics and systemic corticosteroids, are equally important as management strategies in these pandemic times.

Hit or miss: The Dilemma of Specimen Selection for Microbiological Diagnosis of Rhino-Orbital-Cerebral- COVID-Associated Mucormycosis (ROCM-CAM).

BACKGROUND: We diagnosed various cases of rhino-orbital-cerebral- COVID-associated Mucormycosis (ROCM-CAM) during India's second wave of COVID-19. This helped formulate novel suggestions for improving laboratory output, applicable anywhere in the world. METHOD: To diagnose ROCM-CAM by microbiological methods, we used direct microscopy and conventional culture on various clinical samples within the shortest turn-around time. DESIGN: Prospective single-center observational study Participants: patients with ROCM-CAM Results: Of 113 suspected cases of ROCM-CAM during May 2021, direct microscopy and culture could confirm the disease in 87.61% and 44.25% of patients, respectively. The highest pathogen isolation was seen from maxillary bone fragments, FESS-guided biopsy from pterygopalatine fossae, nasal turbinates and nasal mucosal biopsy. Direct microscopy could diagnose the disease in almost 40% of patients within 24 hours and 60% within two days. Conventional cultures yielded Rhizopus spp. (86%) as the commonest fungal pathogen followed by Mucor spp. (12%) within 7 days. Deep tissue biopsies are more useful for rapid diagnosis than superficial specimens. Routine fungal cultures can supplement case detection and help prognosticate survivors. CONCLUSION: The management of ROCM is a surgical emergency. The diagnosis of the condition must therefore be prompt and precise. Despite ongoing antifungal therapy, nasal mucosal tissue, FESSguided, and intra-operative tissue biopsies showed the pathogen's highest diagnostic yield. The diagnostic index improved further when multiple (4-5) high-quality specimens were collected. Nasal swabs and crusts, among the most commonly requested specimens worldwide, were found to have an overall low diagnostic potential.

Mortality and its determinants after an outbreak of post COVID-19 associated rhino-orbito-cerebral mucormycosis in Central India.

AIM: To report cumulative mortality rates using survival analysis from an outbreak of 211 patients with post COVID-19 rhino-orbito-cerebral mucormycosis (ROCM) in central India. METHODS: Case files of eligible patients were evaluated and mucor was identified from deep nasal swabs using freshly prepared KOH mount. All patients underwent contrast enhanced MRI and disease staging was done based on the extent of anatomical involvement. All patients received intravenous Amphotericin B and sinus debridement was done when possible. Orbital exenteration was reserved for patients with advanced orbital disease. RESULTS: The mean age was 50.7 ± 10.2 of which 147 (70%) were men. At presentation, ROCM was limited to sinuses in 72 (34%), orbital extension was seen in 102 (48%) and 31 (15%) had CNS extension. Sinus debridement was possible in 82% cases (n = 173). Thirty-five (16.6%) patients died due to ROCM. The mean follow-up of patients who survived was 126.6 ± 16.4 days. The cumulative mortality rate at day 10 was 4.8% (95%CI = 2.6-8.8%) and increased 13.1% (95%CI = 9.1-18.7%) at day 30 and to 18.4% (95%CI = 13.6-24.8%) at day 60. Majority of deaths (n = 26, 75%) occurred within 1-month of ROCM presentation. Multivariable hazards analysis showed that patients with CNS involvement had a 6.5 times higher risk of death (Hazard Ratio = 6.71, 95% CI = 2.9-15.5, p < 0.001). CONCLUSION: We report significantly lower mortality rates compared to recent literature that varies from 30 to 80% at 1-month follow-up. Timely sinus debridement and systemic Amphotericin B can help reduce mortality. Presence of CNS extension significantly increased the mortality risk with patients with ROCM.

Manifestations of Mucormycosis and Its Complications in COVID-19 Patients: A Case Series Study.

OBJECTIVE: Mucormycosis is an opportunistic fungal disease that affects immunocompromised patients. With the advent of SARS-CoV-2, this opportunistic disease has increased. METHODS: A case series of 47 patients with COVID-19 associated mucormycosis have been analyzed. Demographic information, signs, symptoms, laboratory investigations, imaging studies, and their association with ICU admission and 30-day mortality were assessed. RESULTS: Total number of 47 consecutive rhino-orbital cerebral mucormycosis (ROCM) cases were analyzed. Periorbital swelling was the most common sign among patients. Majority of cases had diabetes. All patients received liposomal Amphotericin B. Debridement was performed for all cases. CONCLUSIONS: SARS-CoV-2 increases the susceptibility to mucormycosis infection in various ways. Uncontrolled level of HbA1c in all patients, even non-diabetic individuals, indicates hyperglycemia over the past three months. Diabetes, orbital exenteration, ptosis, periorbital swelling, DKA, LOC, brain involvement, and mechanical ventilation all correlated with a higher rate of ICU admission and 30-day mortality. In addition, a higher white blood cell count is related to the higher probability of ICU admission. While considering all of the inflammatory laboratory data and HbA1c could help predict 30-day mortality.

Fatality Chooses Its Path Through the Orbit: A Study of Rhino-Orbito-Cerebral Mucormycosis as a Complication of COVID-19 Infection.

Introduction and aim Mucormycosis is a rare but serious angio-invasive infection caused by a group of fungi called mucormycetes and it mainly affects people who are immunocompromised, or patients already infected with other diseases. The dreaded mucormycosis infection has recently gained gross ill-repute for having claimed many lives in coronavirus disease (COVID-19) and/or post-COVID-19 patients. Hence a need was felt to study the development of mucormycosis in COVID-19 patients to better prevent and treat this fungal infection in anticipated future waves of the pandemic. This study also aims to establish an association between COVID-19 positivity, systemic comorbidities, and treatment modalities with the possibility of occurrence of vision and life-threatening mucor infection of the nose, paranasal sinuses, orbit, and brain. Methods This is a hospital-based, retrospective, case-control study. The study reviewed case files of all patients diagnosed with rhino-orbito-cerebral mucormycosis (ROCM) from April 1, 2021, to May 31, 2021. A set of age-matched COVID-19-positive patients hospitalized during the study period with moderate to severe disease were recruited as controls. We addressed factors that could be associated with the development of fungal infection and studied the period between COVID-19 positivity and the onset of ROCM. Results The age of patients in both groups ranged from 40-60 years with 13 females and 17 males. A statistically significant correlation (p-value = 0.032) was found between positive reverse transcription-polymerase chain reaction (RT-PCR) history and use of intravenous (IV) corticosteroids (11 [73.3%] cases and all controls). The mean duration from COVID-19 positivity to the presentation of mucormycosis was 12.10±7.27 days. Uncontrolled blood sugar was found to be the most significant correlation (p-value = 0.003). Mucormycosis is 13.678 times more likely in people with abnormal hemoglobin A1c (HbA1c). Co-morbidities like anemia, chronic kidney disease (CKD), coronary artery disease (CAD), and leukemia were found in controls, but none of these conditions were seen in patients who developed mucormycosis. Conclusion Judicious use of steroids and strict control of blood sugar levels should be emphasized in the management of COVID-19 patients.

A cross-sectional study to describe the spectrum of ocular manifestations and risk factors of mucormycosis presenting to a tertiary hospital of East India.

Purpose: To report the clinico-demographic profile of rhino-orbito-cerebral mucormycosis (ROCM) in patients during the "second wave" of the COVID-19 pandemic in eastern India, and their ophthalmic manifestations at presentation to our tertiary institute. Methods: Cross-sectional study amongst patients presenting to our center based on their hospital records. Demographic information, history related to COVID-19, records of detailed ocular examination, and microbiological, radiological, and histopathological investigation were entered into an online worksheet and analyzed using SPSS 26.0. Results: A total of 219 patients with ROCM were treated from May to September 2021, and 110 of these had ocular manifestations at presentation (50.2%). The age of patients ranged from 22 to 83 years and the mean ± standard deviation (SD) age was 49.9 ± 12.9 years. Ninety (81.8%) patients had been diagnosed with diabetes mellitus, 31 (34%) had hypertension, and 10 had other comorbidities. The duration between the onset of COVID-19 and mucormycosis symptoms was 0 to 60 days with a mean ± SD interval of 20.9 ± 12.6 days. Fifty-six (50.9%) patients had a history of steroid use. Unrelenting ocular or facial pain was the most common presenting symptom, ptosis was the most common anterior segment manifestation, and ophthalmic artery occlusion was the most common posterior segment manifestation. Conclusion: Our data from eastern India reinforces the relationship between COVID-19, diabetes, corticosteroid use, and ROCM. Knowledge of various presenting anterior and posterior segment manifestations of the disease as described in the present study will guide clinicians to recognize the disease early and make every effort to prevent complications.

Corneal manifestations and treatment among patients with COVID-19-associated rhino-orbito-cerebral mucormycosis.

Purpose: TO report the corneal manifestations in patients with COVID-19-associated rhino-orbito-cerebral mucormycosis (ROCM). Methods: This study was a retrospective, observational, and record-based analysis of patients of ROCM with corneal involvement. Results: A total of 220 patients were diagnosed with ROCM over a period of 3 months. Thirty-two patients had developed corneal manifestations. The mean age at diagnosis was 52.84 ± 12.8 years. The associated risk factors were systemic mucormycosis, uncontrolled diabetes, recent COVID-19 infection, and injudicious use of systemic steroids. Twenty-nine patients were known diabetics, 32 had recent COVID-19 infection, and 13 gave a history of injudicious use of steroids. The right eye (RE) was affected in nine patients, the left eye (LE) in 20 patients, and both eyes in three patients. Nine patients had a round-oval corneal ulcer. One patient each had a perforated corneal ulcer with uveal prolapse, sealed perforated corneal ulcer, spontaneously healed limbal perforation, diffuse corneal haze with hyphemia, panophthalmitis, diffuse corneal stromal abscess, limbal ischemia, anterior uveitis with posterior synechiae, inferior corneal facet, and filamentary keratitis. Three patients each had a corneal melt and inferior conjunctival xerosis with chemosis. Orbital exenteration was performed in six patients. Five patients with corneal ulcers healed. Topical eye drops of amphotericin (0.5 mg/ml) cycloplegic, antiglaucoma medications, and lubricant eye drops were started along with systemic antifungals. Conclusion: Central corneal ulcer was the most common manifestation of mucormycosis. A concentration as low as 0.5 mg/ml of amphotericin eye drops was effective in the treatment.

Emergence of Cerebral Mucormycosis in the Post-COVID Period: A Detailed Analysis of Risk Factors, Clinical Progression, and Management of This Opportunistic Fungal Infection.

BACKGROUND: An epidemic of Mucorales was reported following the second wave of COVID-19 in India, and intracranial extension of the same was one of the most dreadful complications. METHODS: A total of 62 patients with cerebral mucormycosis were recruited and followed up till 12 weeks to evaluate the risk factors, incidence, clinical manifestations, management, and prognosis of cerebral mucormycosis. FINDINGS: A median age of 51.5 years with male predominance (74%) was noted. The majority of subjects reported a history of COVID infection (93.5%) and diabetes mellitus (83.87%). The first symptom of mucormycosis appeared after a mean period of 17.63 ± 8.9 days following COVID. Facial swelling and ptosis were the most common symptoms. Only 55% of patients had neurological presentations, and hemiparesis was the most common neurological sign (30.6%). Radiologically, the involvement of maxillary sinus (90.32%) and ethmoid sinus (87.10%) was commonly noted. Cerebral findings included temporal lobe (50%) and parietal lobe (30.06%) involvement, cavernous sinus thrombosis (30.06%), and internal carotid artery thrombosis (22.58%). Acute cerebral infarction was notable in 37% of subjects (p-value=0.0015, significant association with the outcome). Conventional and liposomal amphotericin B were used in 91.94% and 53.23% of patients, respectively. Retrobulbar amphotericin injections used in 11.3% of subjects significantly affected the outcome (p-value=0.03, significant). Posaconazole step-down therapy was used in 72.5% of subjects (p-value=0.0005, significant). Surgical interventions were performed in 53 (85.48%) subjects (p-value=0.004, significant). Functional endoscopic sinus surgery was the most common (in 64.52% of subjects), followed by maxillectomy (20.97% of subjects) and craniotomy (17.7% of subjects). At the end of 12 weeks, 33.87% of patients died and 59.68% were alive; the rest (6.45%) were lost to follow-up. INTERPRETATION: The absence or late presentation of neurological symptoms led to a delayed diagnosis of cerebral mucormycosis. The presence of acute cerebral infarction indicated a worse prognosis. However, there was a significant influence of step-down posaconazole therapy, retrobulbar amphotericin injections, and surgical intervention on the prognosis of cerebral mucormycosis.