Case Report: Rhino-orbital Mucormycosis Related to COVID-19: A Case Series Exploring Risk Factors.

There has been a surge of rhino-orbital mucormycosis cases in India in the wake of the second wave of the COVID-19 pandemic. It has been widely suggested that dysglycemia resulting from diabetes which is a common comorbidity in COVID-19 patients, and indiscriminate steroid use has resulted in this surge. We report a series of 13 cases of rhino-orbital mucormycosis in COVID-19 patients admitted to our center between mid-April and early June 2021. The cases showed a male preponderance, two patients had loss of vision, and four of them showed intracranial extension of disease. Twelve patients had received steroids and 12 had preexisting or newly diagnosed diabetes, both steroid use and diabetes being the most common identified risk factors. Considering other possible risk factors, immunosuppressed state, antiviral or ayurvedic (Indian traditional) medications, and oxygen therapy were not associated with a definite risk of mucormycosis, because they were not present uniformly in the patients. We propose that COVID-19 itself, through molecular mechanisms, predisposes to mucormycosis, with other factors such as dysglycemia or steroid use increasing the risk.

Resolving the equation between mucormycosis and COVID-19 disease.

The COVID-19 patients, both infected and recovered are rapidly contracting mucormycetes infections due to the 'Mucorales' order, under Zygomycetes class of fungi. The mucorales fungi commonly known to exist in our natural surroundings including soil, but the frequency of incidences was never rampant. This sudden spike in infections, is locally known as 'black fungus,' and is affecting various organs, including- eyes, sinuses, nose, brain, skin, intestine, lungs, etc. The severity of situation is ascertainable from the fact that, in certain cases surgical eye/jaws removal persists as the only viable option to avert mortality, as therapeutic interventions are limited. This epidemic situation intrigued experts to investigate the probable reason behind this unpredicted escalation in reported cases, including in recuperated COVID-19 patients, as person-to-person spread of infection is not common. The comparison of physiological parameters in healthy and COVID-19 afflicted patients highlights that the underlying conditions including diabetes mellitus, steroidal therapy, lymphopenia (decreased CD4+ and CD8+ lymphocytes), deregulated cytokine release storm, elevated free iron levels (hemosiderosis) in blood and insulin insensitivity are playing major roles in deteriorating conditions in rarely pathogenic fungal infections. This review is an attempt to explain the rationalities that makes people vulnerable to mucormycetes infection.

A systematic review on SARS-CoV-2-associated fungal coinfections.

A severe pandemic of Coronavirus Disease (COVID-19) has been sweeping the globe since 2019, and this time, it did not stop, with frequent mutations transforming into virulent strains, for instance, B.1.1.7, B.1.351, and B.1.427. In recent months, a fungal infection, mucormycosis has emerged with more fatal responses and significantly increased mortality rate. To measure the severity and potential alternative approaches against black fungus coinfection in COVID-19 patients, PubMed, Google Scholar, World Health Organization (WHO) newsletters, and other online resources, based on the cases reported and retrospective observational analysis were searched from the years 2015-2021. The studies reporting mucormycosis with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) coinfection and/or demonstrating potential risk factors, such as a history of diabetes mellitus or suppressed immune system were included, and reports published in non-English language were excluded. More than 20 case reports and observational studies on black fungus coinfection in COVID-19 patients were eligible for inclusion. The results indicated that diabetes mellitus, hyperglycemic, and immunocompromised COVID-19 patients with mucormycosis were at a higher risk. We found that it was prudent to assess the potential risk factors and severity of invasive mycosis via standardized diagnostic and clinical settings. Large-scale studies need to be conducted to identify early biomarkers and optimization of diagnostic methods has to be established per population and geographical variation. This will not only help clinicians around the world to detect the coinfection in time but also will prepare them for future outbreaks of other potential pandemics.

COVID-19 associated mucormycosis: A Descriptive Multisite Study from India.

BACKGROUND AND AIMS: Mucormycosis is an invasive fungal infection and carries a significant morbidity and mortality. A number of cases of mucormycosis have been reported in association with COVID-19. In this study, a consortium of clinicians from various parts of India studied clinical profile of COVID-19 associated mucormycosis (CAM) and this analysis is presented here. METHODS: Investigators from multiple sites in India were involved in this study. Clinical details included the treatment and severity of COVID-19, associated morbidities, as well as the diagnosis, treatment and prognosis of mucormycosis. These data were collected using google spreadsheet at one centre. Descriptive analysis was done. RESULTS: There were 115 patients with CAM. Importantly, all patients had received corticosteroids. Diabetes was present in 85.2% of patients and 13.9% of patients had newly detected diabetes. The most common site of involvement was rhino-orbital. Mortality occurred in 25 (21.7%) patients. On logistic regression analysis, CT scan-based score for severity of lung involvement was associated with mortality. CONCLUSION: Universal administration of corticosteroids in our patients is notable. A large majority of patients had diabetes, while mortality was seen in ∼1/5th of patients, lower as compared to recently published data.

Rhino-orbital-cerebral-mucormycosis in COVID-19: A systematic review.

Since the onset of COVID-19 pandemic, parallel opportunistic infections have also been emerging as another disease spectrum. Among all these opportunistic infection, mucormycosis has become a matter of concern with its rapid increase of cases with rapid spread as compared to pre-COVID-19 era. Cases have been reported in post-COVID-19-related immune suppression along with the presence of comorbidity which adds on the deadly outcome. There is no systematic review addressing the issue of COVID-19-associated mucormycosis. This is the first systematic review of published studies of mucormycosis associated with COVID-19. The aim was to analyze the real scenario of the disease statement including all the published studies from first November 2019 to 30th June to analyze the contemporary epidemiology, clinical manifestations, risk factor, prognosis, and treatment outcome of COVID-19 associated rhino-orbito-cerebral-mucormycosis. A comprehensive literature search was done in following databases, namely, PubMed, Google Scholar, Scopus, and EMBASE using keywords mucormycosis, rhino orbital cerebral mucormycosis, COVID-19, and SARS-CoV-2 (from November 01, 2019 to June 30, 2021). Our study shows that, while corticosteroids have proved to be lifesaving in severe to critical COVID-19 patients, its indiscriminate use has come with its price of rhino-orbito-cerebral mucormycosis epidemic, especially in India especially in patients with preexisting diabetes mellitus with higher mortality. Corticosteroid use should be monitored and all COVID-19 patients should be closely evaluated/monitored for sequelae of immunosuppression following treatment.

Is there an association between zinc and COVID-19-associated mucormycosis? Results of an experimental and clinical study.

BACKGROUND: The enormous increase in COVID-19-associated mucormycosis (CAM) in India lacks an explanation. Zinc supplementation during COVID-19 management is speculated as a contributor to mucormycosis. We conducted an experimental and clinical study to explore the association of zinc and mucormycosis. METHODS: We inoculated pure isolates of Rhizopus arrhizus obtained from subjects with CAM on dichloran rose Bengal chloramphenicol (DRBC) agar enriched with (three different concentrations) and without zinc. At 24 h, we counted the viable colonies and measured the dry weight of colonies at 24, 48 and 72 h. We also compared the clinical features and serum zinc levels in 29 CAM cases and 28 COVID-19 subjects without mucormycosis (controls). RESULTS: We tested eight isolates of R arrhizus and noted a visible increase in growth in zinc-enriched media. A viable count percentage showed a significantly increased growth in four of the eight isolates in zinc-augmented DRBC agar. A time- and concentration-dependent increase in the mean fungal biomass with zinc was observed in all three isolates tested. We enrolled 29 cases of CAM and 28 controls. The mean serum zinc concentration was below the reference range in all the subjects and was not significantly different between the cases and controls. CONCLUSIONS: Half of the R arrhizus isolates grew better with zinc enrichment in vitro. However, our study does not conclusively support the hypothesis that zinc supplementation contributed to the pathogenesis of mucormycosis. More data, both in vitro and in vivo, may resolve the role of zinc in the pathogenesis of CAM.

Mucormycosis in patients with COVID-19: A cross-sectional descriptive multicentre study from Iran.

PURPOSE: The aim of the study was to report clinical features, contributing factors and outcome of patients with coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM). METHODS: A cross-sectional descriptive multicentre study was conducted on patients with biopsy-proven mucormycosis with RT-PCR-confirmed COVID-19 from April to September 2020. Demographics, the time interval between COVID-19 and mucormycosis, underlying systemic diseases, clinical features, course of disease and outcomes were collected and analysed. RESULTS: Fifteen patients with COVID-19 and rhino-orbital mucormycosis were observed. The median age of patients was 52 years (range 14-71), and 66% were male. The median interval time between COVID-19 disease and diagnosis of mucormycosis was seven (range: 1-37) days. Among all, 13 patients (86%) had diabetes mellitus, while 7 (46.6%) previously received intravenous corticosteroid therapy. Five patients (33%) underwent orbital exenteration, while seven (47%) patients died from mucormycosis. Six patients (40%) received combined antifungal therapy and none that received combined antifungal therapy died. CONCLUSION: Clinicians should be aware that mucormycosis may be complication of COVID-19 in high-risk patients. Poor control of diabetes mellitus is an important predisposing factor for CAM. Systematic surveillance for control of diabetes mellitus and educating physician about the early diagnosis of CAM are suggested.

Mucormycosis and COVID-19: An epidemic within a pandemic in India.

IMPORTANCE: Coronavirus disease (COVID-19) causes an immunosuppressed state and increases risk of secondary infections like mucormycosis. We evaluated clinical features, predisposing factors, diagnosis and outcomes for mucormycosis among patients with COVID-19 infection. METHODS: This prospective, observational, multi-centre study included 47 consecutive patients with mucormycosis, diagnosed during their course of COVID-19 illness, between January 3 and March 27, 2021. Data regarding demography, underlying medical conditions, COVID-19 illness and treatment were collected. Clinical presentations of mucormycosis, imaging and biochemical characteristics and outcome were recorded. RESULTS: Of the 2567 COVID-19 patients admitted to 3 tertiary centres, 47 (1.8%) were diagnosed with mucormycosis. Mean age was 55 ± 12.8years, and majority suffered from diabetes mellitus (n = 36, 76.6%). Most were not COVID-19 vaccinated (n = 31, 66.0%) and majority (n = 43, 91.5%) had developed moderate-to-severe pneumonia, while 20 (42.6%) required invasive ventilation. All patients had received corticosteroids and broad-spectrum antibiotics while most (n = 37, 78.7%) received at least one anti-viral medication. Mean time elapsed from COVID-19 diagnosis to mucormycosis was 12.1 ± 4.6days. Eleven (23.4%) subjects succumbed to their disease, mostly (n = 8, 72.7%) within 7 days of diagnosis. Among the patients who died, 10 (90.9%) had pre-existing diabetes mellitus, only 2 (18.2%) had received just one vaccine dose and all developed moderate-to-severe pneumonia, requiring oxygen supplementation and mechanical ventilation. CONCLUSIONS: Mucormycosis can occur among COVID-19 patients, especially with poor glycaemic control, widespread and injudicious use of corticosteroids and broad-spectrum antibiotics, and invasive ventilation. Owing to the high mortality, high index of suspicion is required to ensure timely diagnosis and appropriate treatment in high-risk populations.

Diabetes, COVID 19 and mucormycosis: Clinical spectrum and outcome in a tertiary care medical center in Western India.

AIMS: Diabetes Mellitus predisposes patients to invasive fungal infections. There has been a recent surge of Mucormycosis with COVID 19 infection particularly in patients with diabetes. This study aims to study the clinical spectrum of CAM (COVID -associated Mucormycosis) with diabetes and subsequent outcomes. MATERIAL AND METHODS: This was a descriptive study conducted at a single COVID Care Centre in India in patients with COVID Associated Mucormycosis from April 12, 2021 to May 31, 2021. RESULTS: Among 953 hospitalized patients with COVID 19 infection, 32 patients had CAM with an incidence of 3.36%. In patients with CAM, 87.5% had Diabetes Mellitus as the most common co-morbidity. The majority of the patients had poor glycemic control with a mean HbA1c of 9.06%. Out of the total study population, 93% had prior exposure to high dose corticosteroids. During the study period, 12.5% patients of CAM did not survive. CONCLUSION: Mucormycosis is an angioinvasive fungal infection with high mortality. The disease has surged in COVID 19 pandemic due to uncontrolled diabetes and improper corticosteroid use.