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

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

COVID-19 and Mucormycosis

In early December 2019, several cases of pneumonia of unknown etiology were reported from Wuhan, Hubei province, China. The disease resembles severe acute respiratory syndrome coronavirus (SARS CoV) of 2012 and was subsequently named SARS CoV-2 causing the 2019-novel coronavirus disease (COVID-19) by the World Health Organization (WHO). The first case of COVID-19 in India was reported on January 30, 2020. In the first wave, daily cases peaked in mid-September 2020 and began to drop by January 2021. However, a second wave beginning in March 2021 was experienced which was much larger than the first, with extreme shortages of hospital beds, oxygen cylinders, and other medicines including vaccines in parts of the country. In the second wave, an association of COVID-19 patients with mucormycosis further complicated the situation. COVID-19 associated mucormycosis (CAM) has been increasingly reported particularly among patients with uncontrolled diabetes. An increase in CAM cases could be probably due to immunosuppression caused by the use of steroids, other immunomodulators like tocilizumab. Rhino-orbitalcerebral mucormycosis is the most common presentation. The most common causative agent isolated is Rhizopus arrhizus. Simple KOH examination with broad, ribbon-like, aseptate hyphae that branch at right angles is diagnostic of mucormycosis. This can be further confirmed by culture examination. However, newer tests like MALDI-TOF for species identification are also being explored. The main treatment modality is surgical debridement, removing all the infected, dead, and necrotic tissue followed by simultaneous administration of antifungal antibiotics in the form of Amphotericin B. Liposomal amphotericin B is the drug of choice, however, if not available, amphotericin B deoxycholate, posaconazole, and isavuconazole can be given for the treatment of CAM. Prognosis and clinical improvement depend upon the stage of disease, the surgical management as well as the availability and administration of antifungal drugs. In media, mucormycosis is being projected as black fungus throughout this pandemic, though it is a misnomer and should not be used in the medical literature. © The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2021.

The battle against fungi: lessons in antifungal stewardship from COVID 19 times

The COVID-19 pandemic has highlighted the detrimental effect of secondary pathogens in patients with a primary viral insult. In addition to superinfections with bacterial pathogens, invasive fungal infections were increasingly reported. The diagnosis of pulmonary fungal infections has always been challenging; however, it became even more problematic in the setting of COVID-19, particularly regarding the interpretation of radiological findings and mycology test results in patients with these infections. Moreover, prolonged hospitalization in ICU, coupled with underlying host factors. such as preexisting immunosuppression, use of immunomodulatory agents, and pulmonary compromise, caused additional vulnerability to fungal infections in this patient population. In addition, the heavy workload, redeployment of untrained staff, and inconsistent supply of gloves, gowns, and masks during the COVID-19 outbreak made it harder for healthcare workers to strictly adhere to preventive measures for infection control. Taken together, these factors favored patient-to-patient spread of fungal infections, such as those caused by Candida auris, or environment-to-patient transmission, including nosocomial aspergillosis. As fungal infections were associated with increased morbidity and mortality, empirical treatment was overly used and abused in COVID-19-infected patients, potentially contributing to increased resistance in fungal pathogens. The aim of this paper was to focus on essential elements of antifungal stewardship in COVID-19 for three fungal infections, COVID-19-associated candidemia (CAC), -pulmonary aspergillosis (CAPA), and -mucormycosis (CAM).

Role of COVID 19 Inflammatory Markers in Rhino-Orbito-Cerebral Mucormycosis: A Case Study in Predisposed Patients at a Designated Nodal Centre.

Mucormycosis is a very morbid and potentially life threatening fungal infection. Sudden emergence and rapidly increasing numbers, of an otherwise rare infection in active Corona virus disease 2019 (COVID-19) or recently recovered patients has made us question the cause for this epidemic in India. This retrospective cohort study was done at Government Ear, Nose and Throat (ENT) hospital, Hyderabad, a designated nodal centre for mucormycosis for the state of Telangana, between April 2021 and June 2021. This study included patients with mucormycosis who had a recent history of COVID-19 infection. Potential predisposing factors (diabetes mellitus, history of oxygen and corticosteroids usage) and inflammatory marker values, predominantly deranged in COVID-19 infection (D-dimer and Serum Ferritin) were evaluated. A correlation between the marker values and susceptibility factors was also studied. Majority of these subjects showed elevated serum markers and had one or more of the predisposing factors for COVID-19 associated mucormycosis (CAM). A significant association was found between elevated marker values and susceptibility factors (diabetes, use of oxygen). Contrary to the popular belief, that the inadvertent use of steroids, use of industrial oxygen or elevated blood sugars caused this epidemic, our study concludes that their role is limited to affecting the extent of morbidity/mortality. B.1.1.7 and B.6.117 variants of severe acute respiratory syndrome coronavirus 2 (SARSCoV2), predominant during the second wave in India, facilitated the fungal invasion and spread by altering the gene expression and inducing inflammatory and immunomodulatory changes.

Post-COVID Mucormycosis Involving Mandible: A Rare Phenomenon.

Mucormycosis is a fungal disease involving predominantly the paranasal sinuses and further spreading to the orbit and cerebral regions. It does rarely affect the pulmonary region and gastrointestinal regions. This disease is seen more in a very serious state, where the tissues undergo necrosis and cause huge morbidity and, in some cases, end up being fatal. The disease was common in individuals with an immune-compromised state, thus more commonly presenting in individuals with uncontrolled diabetes. The disease is usually acquired through coming into contact with spores of the fungus Mucormycetes through the nose, and the fungi invade the paranasal regions, colonize, and spread locally with angio-invasion and relying on host ferritin for survival, thereby causing tissue necrosis. The incidence of mucormycosis had increased considerably post-COVID-19 due to host immune factors. This fungus commonly spreads from paranasal regions to the cranial direction through orbit. The spread is rapid, thus needing early medical and surgical intervention. The spread of infection from the paranasal regions to the caudally placed mandible is very rarely seen. In this paper, we present three cases of mucormycosis spreading caudally and involving the mandibular regions.

Higher proinflammatory responses possibly contributing to suppressed cytotoxicity in patients with COVID-19 associated mucormycosis.

INTRODUCTION: COVID-19 Associated Mucormycosis (CAM), an opportunistic fungal infection, surged during the second wave of SARS Cov-2 pandemic. Since immune responses play an important role in controlling this infection in immunocompetent hosts, it is required to understand immune perturbations associated with this condition for devising immunotherapeutic strategies for its control. We conducted a study to determine different immune parameters altered in CAM cases as compared to COVID-19 patients without CAM. METHODOLOGY: Cytokine levels in serum samples of CAM cases (n = 29) and COVID-19 patients without CAM (n = 20) were determined using luminex assay. Flow cytometric assays were carried out in 20 CAM cases and 10 controls for determination of frequency of NK cells, DCs, phagocytes, T cells and their functionalities. The cytokine levels were analyzed for their association with each other as well as with T cell functionality. The immune parameters were also analyzed with respect to the known risk factors such as diabetes mellitus and steroid treatment. RESULTS: Significant reduction in frequencies of total and CD56 + CD16 + NK cells (cytotoxic subset) was noted in CAM cases. Degranulation responses indicative of cytotoxicity of T cell were significantly hampered in CAM cases as compared to the controls. Conversely, phagocytic functions showed no difference in CAM cases versus their controls except for migratory potential which was found to be enhanced in CAM cases. Levels of proinflammatory cytokines such as IFN-γ, IL-2, TNF-α, IL-17, IL-1ß, IL-18 and MCP-1 were significantly elevated in cases as compared to the control with IFN-γ and IL-18 levels correlating negatively with CD4 T cell cytotoxicity. Steroid administration was associated with higher frequency of CD56 + CD16- NK cells (cytokine producing subset) and higher MCP-1 levels. Whereas diabetic participants had higher phagocytic and chemotactic potential and had higher levels of IL-6, IL-17 and MCP-1. CONCLUSION: CAM cases differed from the controls in terms of higher titers of proinflammatory cytokines, reduced frequency of total and cytotoxic CD56 + CD16 + NK cell. They also had reduced T cell cytotoxicity correlating inversely with IFN-γ and IL-18 levels, possibly indicating induction of negative feedback mechanisms while diabetes mellitus or steroid administration did not affect the responses negatively.

Fungal Diseases and COVID-19

The physiological factors of COVID-19 infection and the environmental factors of treatment have predisposed a larger patient population to fungal infections. In this review, we provide an overview of the three most frequently documented fungal infections associated with COVID-19: aspergillosis, mucormycosis, and candidemia. For all three secondary infections, we review the literature making efforts to determine the incidence of infection, physiological or environmental causes of co-infection with COVID-19, and the mortality of infection both with and without COVID-19. These infections vary in their etiology in association with COVID-19 infection, in addition to their recommended treatments and mortality. Ultimately, we demonstrate the importance of early diagnosis of secondary infections and the proper identification of fungal pathogens for treatment purposes, while also highlighting research gaps in this new field. © 2023 Nova Science Publishers, Inc.

Mucormycosis in patients with COVID-19 in Russia: the results of a prospective multi-center study.

We present the results of a prospective multicenter study of risk factors, etiology, clinical features, and treatment outcomes for mucormycosis in patients with COVID-19 (COVID-M) in the Russian Federation. The study included 60 adult patients with COVID-M. To analyze risk factors for COVID-M, we conducted a case-control study. The control group included 60 adult patients with COVID-19 without mucormycosis. To analyze the clinical manifestations of COVID-M, we created a control group of hematological patients with mucormycosis examined in 2011-2020. In patients with COVID-19, the risk of developing mucormycosis was significantly increased with diabetes mellitus (OR=49) and overweight (OR=4,75), as well as with the use of high (>=100 mg per day for prednisolone) doses of glucocorticosteroids (OR= 4,762), especially >=10 days (OR=25,4). The main localization of mucormycosis in patients with CO-VID-19 was the paranasal sinuses (95%) and the orbit (68%). Involvement of >=2 organs was identified in 70% of patients. The main causative agents of mucormycosis were Rhizopus arrhizus (43%) and unidentified mucormycetes (36%). 90-days overall survival of patients with mucormycosis and COVID-19 - 71%. The stay in the ICU (p=0,01), the use of mechanical ventilation (p=0,0481), the presence of CVC (p=0,049), CNS damage (p=0,016) and >= 2 organs (p=0,048) significantly worsened the prognosis of the disease. The best prognosis was in patients who received antifungal therapy (p=0,03875) and surgical treatment (p=0,046).Copyright © 2022 Authors. All rights reserved.

Mucormycosis in patients with COVID-19 in Russia: the results of a prospective multi-center study

We present the results of a prospective multicenter study of risk factors, etiology, clinical features, and treatment outcomes for mucormycosis in patients with COVID-19 (COVID-M) in the Russian Federation. The study included 60 adult patients with COVID-M. To analyze risk factors for COVID-M, we conducted a case-control study. The control group included 60 adult patients with COVID-19 without mucormycosis. To analyze the clinical manifestations of COVID-M, we created a control group of hematological patients with mucormycosis examined in 2011–2020. In patients with COVID-19, the risk of developing mucormycosis was significantly increased with diabetes mellitus (OR=49) and overweight (OR=4,75), as well as with the use of high (≥100 mg per day for prednisolone) doses of glucocorticosteroids (OR= 4,762), especially ≥10 days (OR=25,4). The main localization of mucormycosis in patients with CO-VID-19 was the paranasal sinuses (95%) and the orbit (68%). Involvement of ≥2 organs was identified in 70% of patients. The main causative agents of mucormycosis were Rhizopus arrhizus (43%) and unidentified mucormycetes (36%). 90-days overall survival of patients with mucormycosis and COVID-19 – 71%. The stay in the ICU (p=0,01), the use of mechanical ventilation (p=0,0481), the presence of CVC (p=0,049), CNS damage (p=0,016) and ≥ 2 organs (p=0,048) significantly worsened the prognosis of the disease. The best prognosis was in patients who received antifungal therapy (p=0,03875) and surgical treatment (p=0,046). © 2022 Authors. All rights reserved.

Mucormycosis in patients with COVID-19 in Russia: the results of a prospective multi-center study.

We present the results of a prospective multicenter study of risk factors, etiology, clinical features, and treatment outcomes for mucormycosis in patients with COVID-19 (COVID-M) in the Russian Federation. The study included 60 adult patients with COVID-M. To analyze risk factors for COVID-M, we conducted a case-control study. The control group included 60 adult patients with COVID-19 without mucormycosis. To analyze the clinical manifestations of COVID-M, we created a control group of hematological patients with mucormycosis examined in 2011-2020. In patients with COVID-19, the risk of developing mucormycosis was significantly increased with diabetes mellitus (OR=49) and overweight (OR=4,75), as well as with the use of high (>=100 mg per day for prednisolone) doses of glucocorticosteroids (OR= 4,762), especially >=10 days (OR=25,4). The main localization of mucormycosis in patients with CO-VID-19 was the paranasal sinuses (95%) and the orbit (68%). Involvement of >=2 organs was identified in 70% of patients. The main causative agents of mucormycosis were Rhizopus arrhizus (43%) and unidentified mucormycetes (36%). 90-days overall survival of patients with mucormycosis and COVID-19 - 71%. The stay in the ICU (p=0,01), the use of mechanical ventilation (p=0,0481), the presence of CVC (p=0,049), CNS damage (p=0,016) and >= 2 organs (p=0,048) significantly worsened the prognosis of the disease. The best prognosis was in patients who received antifungal therapy (p=0,03875) and surgical treatment (p=0,046).Copyright © 2022 Authors. All rights reserved.

COVID-19-associated rhino-orbital mucormycosis (CAROM)—a case report

BackgroundThere has been a rapid rise in the number of COVID-19-associated rhino-orbital mucormycosis (CAROM) cases especially in South Asian countries, to an extent that it has been considered an epidemic among the COVID-19 patients in India. As of May 13, 2021, 101 CAROM cases have been reported, of which 82 cases were from India and 19 from the rest of the world. On the other hand, pulmonary mucormycosis associated with COVID-19 has a much lesser reported incidence of only 7% of the total COVID-19-associated mucormycosis cases (Singh AK, Singh R, Joshi SR, Misra A, Diab Metab Syndr: Clin Res Rev, 2021). This case report attempts to familiarize the health care professionals and radiologists with the imaging findings that should alarm for follow-up and treatment in the lines of CAROM.Case presentationRhino-orbital mucormycosis (ROM) is a manifestation of mucormycosis that is thought to be acquired by inhalation of fungal spores into the paranasal sinuses. Here, we describe a 55-year-old male, post COVID-19 status with long standing diabetes who received steroids and ventilator therapy for the management of the viral infection. Post discharge from the COVID-19 isolation ICU, the patient complained of grayish discharge from the right nostril and was readmitted to the hospital for the nasal discharge. After thorough radiological and pathological investigation, the patient was diagnosed with CAROM and managed.ConclusionUncontrolled diabetes and imprudent use of steroids are both contributing factors in the increased number of CAROM cases. Our report emphasizes on the radiological aspect of CAROM and reinforces the importance of follow-up imaging in post COVID-19 infection cases with a strong suspicion of opportunistic infections.

Mucormycosis, past and present: a comprehensive review.

Mucormycosis is an emerging opportunistic angioinvasive fungal infection. Predisposing factors such as diabetes, neutropenia, long-term corticosteroid therapy, solid organ transplantation and immunosuppression contribute to its occurrence. This disease was not of significant concern prior to the COVID-19 pandemic, but gained prominence due to infections in COVID-19 patients. Mucormycosis needs special attention and coordinated efforts of the scientific community and medical professionals to reduce morbidity and mortality. Here we present an overview of the epidemiology and prevalence of mucormycosis in the pre- and post-COVID-19 eras, the factors that contributed to the abrupt increase in COVID-19-associated mucormycosis (CAM), the actions taken by the regulatory agencies (including Code Mucor and CAM registry), the existing diagnostic tools and CAM management strategies.

The devastating effects of the COVID-19 pandemic have been further enhanced by various secondary illnesses, particularly opportunistic fungal infections such as mucormycosis. Mucormycosis or 'black fungus' primarily affects people with weakened immunity, those with medical conditions such as diabetes or cancer and those who use medications that reduce the body's capacity to resist infections and disease. The infection starts in the sinuses or the lungs after breathing in spores of the black fungus from the air. In just 2 months between 5 May and 12 July 2021, this uncommon but fatal fungal illness was responsible for 41,512 cases and 3554 fatalities in India alone. The government of India declared a mucormycosis epidemic in May 2021. The majority of such cases occurred during active SARS-CoV-2 outbreaks in India in 2021. Black fungus took over while the host defenses were compromised and the globe was preoccupied tackling the COVID-19 pandemic. Steroids prescribed in amounts and time spans that far exceeded WHO recommendations to manage severe COVID-19 cases, potentially weakened patients' immune systems, and raised blood sugar levels making them vulnerable to fungal invasion. Early diagnosis and treatment are the keys to a patient's survival. Simple means such as maintaining hygienic conditions, avoiding contact with an infected person, judiciously using steroid medications and antibiotics and properly managing high blood sugar can help protect an individual from black-fungus infection.

Effectiveness of facial palsy protocol among patient with mucormycosis following COVID-19: A case study.

A 41-year-old male with a history of diabetes mellitus presented with right facial palsy post COVID-19 Associated Mucormycosis. A 4-week physiotherapeutic intervention; ice therapy, Mime therapy, Facial Soft Tissue Manipulation, and Facial Proprioceptive Neuromuscular Stimulation, showed improvement in the symptoms of patient and scores of House- Brackman Facial Grading Scale.

COVID-19 associated multisystemic mucormycosis from India: a multicentric retrospective study on clinical profile, predisposing factors, cumulative mortality and factors affecting outcome.

PURPOSE: The clinical course of COVID-19 has been complicated by secondary infections, including bacterial and fungal infections. The rapid rise in the incidence of invasive mucormycosis in these patients is very much concerning. COVID-19-associated mucormycosis was detected in huge numbers during the second wave of the COVID-19 pandemic in India, with several predisposing factors indicated in its pathogenesis. This study aimed to evaluate the epidemiology, predisposing factor, cumulative mortality and factors affecting outcomes among the coronavirus disease COVID-19-associated mucormycosis (CAM). METHODS: A multicenter retrospective study across three tertiary health care centers in Southern part of India was conducted during April-June 2021. RESULTS: Among the 217 cases of CAM, mucormycosis affecting the nasal sinuses was the commonest, affecting 95 (44%) of the patients, orbital extension seen in 84 (38%), pulmonary (n = 25, 12%), gastrointestinal (n = 6, 3%), isolated cerebral (n = 2) and disseminated mucormycosis (n = 2). Diabetes mellitus, high-dose systemic steroids were the most common underlying disease among CAM patients. The mucormycosis-associated case-fatality at 6 weeks was 14%, cerebral or GI or disseminated mucormycosis had 9 times higher risk of death compared to other locations. Extensive surgical debridement along with sequential antifungal drug treatment improved the survival in mucormycosis patients. CONCLUSION: Judicious and appropriate management of the predisposing factor and factors affecting mortality associated with CAM with multi-disciplinary approach and timely surgical and medical management can be much helpful in achieving a successful outcome.

Multimodal analysis of the COVID-19-associated mucormycosis outbreak in Delhi, India indicates the convergence of clinical and environmental risk factors.

BACKGROUND: The aetiology of the major outbreak of COVID-19-associated mucormycosis (CAM) in India in spring 2021 remains incompletely understood. Herein, we provide a multifaceted and multi-institutional analysis of clinical, pathogen-related, environmental and healthcare-related factors during CAM outbreak in the metropolitan New Delhi area. METHODS: We reviewed medical records of all patients diagnosed with biopsy-proven CAM (n = 50) at 7 hospitals in the New Delhi, and NCR area in April-June 2021. Two multivariate logistic regression models were used to compare clinical characteristics of CAM cases with COVID-19-hospitalised contemporary patients as controls (n = 69). Additionally, meteorological parameters and mould spore concentrations in outdoor air were analysed. Selected hospital fomites were cultured. Mucorales isolates from CAM patients were analysed by ITS sequencing and whole-genome sequencing (WGS). RESULTS: Independent risk factors for CAM identified by multivariate analysis were previously or newly diagnosed diabetes mellitus, active cancer and severe COVID-19 infection. Supplemental oxygen, remdesivir therapy and ICU admission for COVID-19 were associated with reduced CAM risk. The CAM incidence peak was preceded by an uptick in environmental spore concentrations in the preceding 3-4 weeks that correlated with increasing temperature, high evaporation and decreasing relative humidity. Rhizopus was the most common genus isolated, but we also identified two cases of the uncommon Mucorales, Lichtheimia ornata. WGS found no clonal population of patient isolates. No Mucorales were cultured from hospital fomites. CONCLUSIONS: An intersection of host and environmental factors contributed to the emergence of CAM. Surrogates of access to advanced COVID-19 treatment were associated with lower CAM risk.

Alternating pattern of rhino-orbital-cerebral mucormycosis with COVID-19 in diabetic patients.

PURPOSE: Our aim was to analyze the patients with diabetic rhino-orbital-cerebral mucormycosis that we have treated in our clinic in the last 5 years, and to reveal the altering conditions with COVID-19. MATERIALS AND METHODS: A retrospective study was conducted on 39 rhino-orbital-cerebral mucormycosis (ROCM) patients with diabetes mellitus between 2017 and 2022. The patients were divided into two groups as those associated with and not associated with COVID-19 and compared. RESULTS: Thirty-nine diabetic patients were included in the study, with 15 (38.5%) of them being COVID-19 associated mucormycosis (CAM) group. CAM patients showed higher orbital involvement and cavernous sinus involvement (p = 0.002 and p = 0.013, respectively). The mortality rate in the non-COVID-19 associated mucormycosis (non-CAM) group was statistically higher in patients with intracranial and cavernous sinus involvement (p = 0.015 and p = 0.033, respectively). The difference between the overall survival of the CAM patients and non-CAM patients was not statistically significant (p = 0.741). CONCLUSIONS: With COVID-19, progressive mucormycosis accompanied by orbital and intracranial involvement is observed more frequently. However, on the contrary, the mortality rate in COVID-19-associated mucormycosis is considerably lower than expected. The fact that temporary immune suppression can be ameliorated with adequate supportive treatment and liposomal amphotericin-B which can be given to patients in high doses may explain this situation. It has been attained hints that the essential factor in the treatment of COVID-19-associated ROCM is the control of the underlying disease and to be cautious in the decision of early aggressive surgery.

Focusing COVID-19-associated mucormycosis: a major threat to immunocompromised COVID-19.

COVID-19 disease has been identified to cause remarkable increase of mucormycosis infection cases in India, with the majority of cases being observed in individuals recovering from COVID-19. Mucormycosis has emanated as an outcome of the recent COVID-19 pandemic outbreak as rapidly developing fatal illness which was acquired by Mucorales fungus which is a subcategory of molds known as mucormycetes. Mucormycosis is one of the serious, sporadic mycotic illnesses which is a great threat to immunocompromised COVID-19 patients and affects people of all ages, including children with COVID-19 infections. This is associated with tissue damaging property and, therefore, causes serious clinical complications and elevated death rate. The COVID-19-associated mucormycosis or "black fungus" are the terms used interchangeably. The rapid growth of tissue necrosis presenting as "rhino-orbital-cerebral, pulmonary, cutaneous, gastrointestinal, and disseminated disease" are various clinical forms of mucormycosis. The patient's prognosis and survival can be improved with proper surgeries using an endoscopic approach for local tissue protection in conjunction with course of appropriate conventional antifungal drug like Amphotericin-B and novel drugs like Rezafungin, encochleated Amphotericin B, Orolofim, and SCY-078 which have been explored in last few years. This review provides an overview of mucormycosis including its epidemiology, pathophysiology, risk factors, its clinical forms, and therapeutic approaches for disease management like antifungal therapy, surgical debridement, and iron chelators. The published patents and ongoing clinical trials related to mucormycosis have also been mentioned in this review.

Perturbations of immune landscape in COVID-19 associated mucormycosis.

BACKGROUND: A rise in secondary fungal infections during the COVID-19 pandemic necessitates a deeper understanding of the associated immunological perturbations. OBJECTIVES: To evaluate the clinical and immunological characteristics observed in patients with COVID-19 associated mucormycosis (CAM) infection. PATIENTS/ METHODS: Cases of mucormycosis with or post-COVID-19 infection were compared with cases of acute COVID-19 and convalescent COVID-19. Lymphocyte subsets, cytokines and other laboratory markers were compared between the groups. RESULTS: The frequency of proposed risk factors for CAM was diabetes mellitus (77%), recent history of steroid use (69%) and hypoxia during COVID-19 infection (52%). Iron metabolism was dysregulated in CAM patients with low TIBC and total iron. Further, CAM was accompanied with lymphopenia with drastic reduction in B cell counts; however, plasmablasts were not altered. Further, CAM patients had low immunoglobulin levels and antibodies specific to mucor peptide did not increase in CAM suggesting dysfunction in B-cell response. There was increase in activated effector cytotoxic CD8 T cells and NK cells in CAM compared with COVID-19 infection and healthy controls. Among T helper cells, Tregs were reduced and Th-1 frequency was increased in CAM compared with COVID-19 infection. A distinct cytokine signature was evident in CAM with increase in IL-1ß, IFN-γ, IL-6, IL-22, IL-17A, IL-10, IL-2, IL-8, IL-7, IL-21 and GM-CSF. CONCLUSION: This is the first study on immunophenotyping in CAM suggesting the need for long-term monitoring of B-cell function after SARS-CoV-2 in patients with dysregulated glycaemic control and the possible benefit of therapeutic supplementation with intravenous immunoglobulins in CAM.