Immune and metabolic perturbations in COVID-19-associated pulmonary mucormycosis: A transcriptome analysis of innate immune cells.

BACKGROUND AND OBJECTIVES: The mechanisms underlying COVID-19-associated pulmonary mucormycosis (CAPM) remain unclear. We use a transcriptomic analysis of the innate immune cells to investigate the host immune and metabolic response pathways in patients with CAPM. PATIENTS AND METHODS: We enrolled subjects with CAPM (n = 5), pulmonary mucormycosis (PM) without COVID-19 (n = 5), COVID-19 (without mucormycosis, n = 5), healthy controls (n = 5) without comorbid illness and negative for SARS-CoV-2. Peripheral blood samples from cases were collected before initiating antifungal therapy, and neutrophils and monocytes were isolated. RNA sequencing was performed using Illumina HiSeqX from monocytes and neutrophils. Raw reads were aligned with HISAT-2 pipeline and DESeq2 was used for differential gene expression. Gene ontology (GO) and metabolic pathway analysis were performed using Shiny GO application and R packages (ggplot2, Pathview). RESULTS: The derangement of core immune and metabolic responses in CAPM patients was noted. Pattern recognition receptors, dectin-2, MCL, FcRγ receptors and CLEC-2, were upregulated, but signalling pathways such as JAK-STAT, IL-17 and CARD-9 were downregulated; mTOR and MAP-kinase signalling were elevated in monocytes from CAPM patients. The complement receptors, NETosis, and pro-inflammatory responses, such as S100A8/A9, lipocalin and MMP9, were elevated. The major metabolic pathways of glucose metabolism-glycolysis/gluconeogenesis, pentose phosphate pathway, HIF signalling and iron metabolism-ferroptosis were also upregulated in CAPM. CONCLUSIONS: We identified significant alterations in the metabolic pathways possibly leading to cellular iron overload and a hyperglycaemic state. Immune responses revealed altered recognition, signalling, effector functions and a pro-inflammatory state in monocytes and neutrophils from CAPM patients.

Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

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

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

Treatment of pulmonary mucormycosis with adjunctive nebulized amphotericin B (MUCONAB trial): Results of an open-label randomized controlled trial.

BACKGROUND: The role of nebulized amphotericin B (NAB) in managing pulmonary mucormycosis (PM) is unknown. METHODS: In this open-label trial, we randomized PM subjects to receive either intravenous liposomal amphotericin B (control arm, 3-5 mg/kg/day) alone or along with nebulized amphotericin B deoxycholate (NAB, 10 mg twice a day, every alternate day). The primary outcomes were: (1) overall response ('success' [complete or partial response] or 'failure' [stable disease, progressive disease, or death]) at 6 weeks; and (2) the proportion of subjects with adverse events (AE). The key secondary outcome was 90-day mortality. We performed a modified intention-to-treat (mITT) analysis where we included only subjects receiving at least a single dose of NAB. RESULTS: Fifteen and 17 subjects were randomized to the control and NAB arms; two died before the first dose of NAB. Finally, we included 30 subjects (15 in each arm; mean age 49.8 years; 80% men) for the mITT analysis. Diabetes mellitus (n = 27; 16/27 were COVID-19-associated PM) was the most common predisposing factor. The overall treatment success was not significantly different between the control and the NAB arms (71.4% vs. 53.3%; p = .45). Twenty-nine subjects experienced any AE, but none discontinued treatment. The 90-day mortality was not significantly different between the control (28.6%) and NAB arm (53.3%; p = .26). CONCLUSION: Adjunctive NAB was safe but did not improve overall response at 6 weeks. A different dosing schedule or nebulized liposomal amphotericin B may still need evaluation. More research is needed to explore other treatment options for PM.

Hyphae, pseudohyphae, yeasts, spherules, spores, and more: A review on the morphology and pathology of fungal and oomycete infections in the skin of domestic animals.

Fungi are among the most common infectious agents affecting the skin of animals. The skin can serve as a port of entry for fungal infections, which can eventually become disseminated. In some regions of the world, oomycetes, such as Pythium and Lagenidium, are also responsible for a significant number of severe cutaneous infections. Histologic evaluation of fungal morphology, including size, shape, septation, branching, and budding characteristics, combined with the distribution of inflammatory infiltrates within different skin layers can potentially identify etiologic agents, guiding selection of antifungals and additional diagnostics. Fungal infections of the skin surface are typically caused by Malassezia and rarely Candida, with opportunistic fungi also capable of colonizing the skin surface, especially when the barrier is broken. Folliculocentric infections, caused by dermatophytes, result in mild to severe inflammation and can occasionally penetrate deep into the skin. A wide range of fungi, including agents of hyalohyphomycosis, phaeohyphomycosis, and dimorphic fungal infections, as well as oomycetes, result in nodular cutaneous and subcutaneous lesions. With the occasional exception of dimorphic fungi, fungal speciation often requires cultures performed on fresh tissues. However, molecular techniques such as pan-fungal polymerase chain reaction on paraffin blocks is becoming an increasingly useful tool to distinguish between cutaneous fungal pathogens. This review focuses on describing the clinical and histologic features of the most common fungal and oomycete infections affecting the skin of animals, divided according to distribution patterns of lesions and fungal or oomycete morphology.

Mucormycosis in Human Immunodeficiency Virus-Infected Individuals: A Systematic Review of Case Reports.

Mucormycosis in human immunodeficiency virus (HIV) infection is uncommon; notably, many cases have additional predisposing factors. Whether mucormycosis differs in HIV-affected individuals with and without additional risk factors (e.g., neutropenia, diabetes mellitus, and transplantation) remains unclear. In this systematic review, we identified 94 cases of HIV and mucormycosis classifiable into three groups: (1) HIV with additional risk factors (n = 50), (2) intravenous drug users (IVDU, n = 24), and (3) no other risk factor (n = 19) for mucormycosis. The most common presentation in IVDU was renal (41.7%) and cerebral mucormycosis (39.2%), whereas rhino-orbital mucormycosis (ROM, 4.2%) was uncommon. In the other two groups, ROM was the most common presentation. Rhizopus was the most frequently isolated Mucorales; however, in IVDU, Lichtheimia was the most common. The overall mortality was 53% and not significantly different in the three groups. Mucormycosis in HIV-infected individuals is rare without additional risk factors or IVDU.

Unusual orbital mucormycosis due to pecking injury: clinical characteristics and outcomes of four immunocompetent pediatric patients.

Mucormycosis is a serious fungal infection caused by fungi in the order of Mucorales. Orbital mucormycosis occurs more frequently in rhino-orbital, sino-orbital, and rhino-orbito-cerebral forms of the disease, while isolated orbital mucormycosis is much less common. Herein, we present four cases of immunocompetent children who developed primary cutaneous mucormycosis, which subsequently invaded and progressed to orbital mucormycosis following direct traumatic injury caused by pecking from Acridotheres tristis (Common Myna). Given the low prevalence of orbital mucormycosis in healthy children, an unknown source of infection and delayed diagnosis followed by late therapeutic interventions could result in life-threatening conditions and serious sequelae.

Coronavirus Disease 2019-Associated Mucormycosis: Risk Factors and Mechanisms of Disease.

The severe surge of coronavirus disease 2019 (COVID-19) cases on the Indian subcontinent in early 2021 was marked by an unusually high number of COVID-19-associated mucormycosis (CAM) cases reported during this same period. This is significantly higher than predicted based on available data about prevalence and risk factors for this condition. This may be due to an unusual alignment of multiple risk factors for this condition. There is high background prevalence of mucormycosis in India likely from a high prevalence of risk factors, including undiagnosed or poorly controlled diabetes. COVID-19-induced immune dysregulation and immune suppression from steroid therapy increase the risk. The role of environmental exposure is unclear. System factors such as lack of access to healthcare during a pandemic may result in delayed diagnosis or suboptimal management with potentially poor outcomes. Here, we review currently identified risk factors and pathogenesis of CAM in a pandemic surge.

Characterizing patients with rare mucormycosis infections using real-world data.

BACKGROUND: Invasive mucormycosis (IM) is a rare and often life-threatening fungal infection, for which clinical and epidemiological understanding is lacking. Electronic health record (EHR) data can be utilized to elucidate large populations of patients with IM to address this unmet need. This study aimed to descriptively assess data on patients with IM using the Optum® EHR dataset. METHODS: US patient data from the Optum® deidentified EHR dataset (2007-2019) were analyzed to identify patients with IM. Patients with hematologic malignancies (HM), at high risk of IM, were selected and sorted by IM diagnosis (ICD9 117.7; ICD10 B46). Demographics, comorbidities/other diagnoses, and treatments were analyzed in patients with IM. RESULTS: In total, 1133 patients with HM and IM were identified. Most were between 40 and 64 years of age, Caucasian, and from the Midwest. Essential primary hypertension (50.31%) was the most common comorbidity. Of the 1133 patients, only 33.72% were prescribed an antifungal treatment. The most common antifungal treatments were fluconazole (24.27%) and posaconazole (16.33%), which may have been prophylactic, and any AmB (15.62%). CONCLUSIONS: A large population of patients with IM were identified, highlighting the potential of analyzing EHR data to investigate epidemiology, diagnosis, and the treatment of apparently rare diseases.

Could cattle dung burning have contributed to the epidemic of COVID-19-associated mucormycosis in India? Results of an experimental aero-mycological study.

BACKGROUND: Several hypotheses have been proposed for explaining the outbreak of coronavirus disease 2019 (COVID-19)-associated mucormycosis in India, including the burning of cattle dung cakes, though no study has yet been conducted to support this claim. METHODS: We conducted an aero-mycological study to evaluate whether Mucorales in the air increased during or after burning cattle dung cakes. We further compared the growth of Mucorales in the indoor air samples from houses with and without cattle. We also cultured fresh and dried cattle dung and soil samples for Mucorales. RESULTS: We noted no significant difference in the proportion of air samples growing Mucorales during (4/22 [18.2%]) and after (3/2 [13.6%]) cattle dung burning than that collected immediately before (4/22 [18.2%]). Mucorales were isolated in 15.4% of the indoor air samples obtained from different houses (both rural and urban); the proportion of samples growing Mucorales was not significantly different in households with and without cattle. We also observed growth of Mucorales in 6 of the 8 [75%] fresh and 3 of the 6 [50%] dried dung samples. The most common Mucorales isolated from soil and dung samples was Lichtheimia corymbifera, while Rhizopus arrhizus was the most common species isolated from indoor air samples. CONCLUSIONS: We found no significant increase in the proportion of air samples growing Mucorales during or after burning cattle dung cake than that before. It seems unlikely that cattle dung burning contributes to the occurrence of mucormycosis.

Increasing Incidence of mucormycosis in Spanish inpatients from 1997 to 2018.

BACKGROUND: Mucormycosis is a worldwide angio-invasive fungal infection that is associated with high morbidity and mortality. A few European studies have focused on the epidemiology. METHODOLOGY: A retrospective longitudinal descriptive study was performed with inpatients diagnosed with mucormycosis (ICD-9-CM, code 117.7, cases 1997-2015; and ICD-10, code B46, cases 2016-2018; along with length of hospital stay) in Spanish public hospitals between 1 January 1997 and 31 December 2018. Data were obtained from the Minimum Basic Data Set (CMBD in Spanish). PRINCIPAL FINDINGS: A total of 962 patients were recorded; 665 were men. The mean age (±SD) was 55 ± 18.8 years. The annual incidence rate increased from 0.74 to 1.24 cases per million person-years. The lethality rate was 31.3%. Renal failure (41.6%) and haematological malignancy (36.3%) were the main factors involved. CONCLUSIONS: Mucormycosis is a rare infectious disease in Spain, but it has had a significantly increased incidence in the last two decades. Being an adult male and having diabetes, neoplasm or renal failure are the main factors associated. High mortality is usually associated mainly with haematological malignancy and renal failure. CMBD studies could be an efficient tool for assessing changes in the epidemiology of mucormycosis.

Treatment and economic burden of mucormycosis in China: Case report review and burden estimation.

WHAT IS KNOWN AND OBJECTIVE: Mucormycosis is an opportunistic fungal infection associated with low incidence but high mortality. Few studies have shown the treatment and disease burden of mucormycosis in China. This study aims at collecting all the reported cases to describe the characteristics and treatment patterns and to assess the economic burden of mucormycosis in China. METHODS: We conducted a literature review of mucormycosis case reports in Chinese patients to summarize the characteristics and treatment patterns of the disease in China. An economic model was built to evaluate the total cost of mucormycosis per person, including direct medical cost, direct non-medical cost and indirect cost. RESULTS AND DISCUSSION: A total of 676 case reports showed that the most common type of mucormycosis was pulmonary mucormycosis (299/676, 44.2%), and rhinocerebral mucormycosis had the highest case fatality rate (122/185, 68.5%). Among those who used empiric therapies, 48.8% (231/473) did not include anti-mucor drugs; 79.8% (336/421) of the therapies include amphotericin B (AMB) or AMB-lipo after detection of mucormycetes; 98.6% (69/70) of the reported adverse events were associated with AMB and AMB-lipo. The duration of treatment ranged from 90 to 180 days; the length of stay ranged from 22 to 95 days. The average total cost per patient was 166 thousand Chinese Yuan (CNY), of which 93.1% was the direct medical cost (155 thousand CNY). WHAT IS NEW AND CONCLUSION: There are a limited number of antifungal treatment options for mucormycosis in China. This study highlights the critical need to introduce innovative and broader spectrum antifungal drugs with improved safety, better clinical efficacy, easier administration and reduced economic burden to Chinese mucormycosis patients.

Serum glucose-regulated protein 78 (GRP78) levels in COVID-19-associated mucormycosis: results of a case-control study.

BACKGROUND: In experimental models, the expression of glucose-regulated protein 78 (GRP78) in endothelial cells played a role in the pathogenesis of mucormycosis. However, the role of GRP78 in COVID-19-associated mucormycosis (CAM) has not been studied. We hypothesized that serum GRP78 levels are elevated in subjects with CAM. OBJECTIVE: To compare the serum GRP78 levels in subjects with CAM and COVID-19 controls without mucormycosis. DESIGN AND SETTING: We performed a hospital-based, case-control study between 1 April 2021 and 31 May 2021. PARTICIPANTS: We enrolled 24 subjects each of CAM and COVID-19 subjects without mucormycosis. We also measured serum GRP78 levels in ten healthy controls. EXPOSURE: The primary exposure studied was serum GRP78 concentration, estimated using a commercially available ELISA kit in stored serum samples. RESULTS: We found the mean ± standard deviation (SD) serum GRP78 levels significantly higher (p = 0.0001) among the CAM (374.3 ± 127.3 pg/mL) than the COVID-19 (246.4 ± 67.0 pg/mL) controls. The proportion of subjects with an abnormal GRP78 level (> mean [184.8 pg/mL] plus two SD [23.2 pg/mL] of GRP78 from healthy participants) was 87.5% and 45.8% in the CAM group and COVID-19 controls, respectively. Serum GRP78 level was independently associated with CAM (odds ratio 1.011; 95% confidence interval [1.002-1.019]) after adjusting for diabetes mellitus and hypoxemia during acute COVID-19. CONCLUSION: Serum GRP78 levels were significantly higher in CAM than in COVID-19 controls. Further studies are required to the role of GRP78 in the pathogenesis of CAM.

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

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

Role of flexible bronchoscopy in the diagnosis of invasive fungal infections.

BACKGROUND: There are sparse data on the role of flexible bronchoscopy (FB) in diagnosing invasive mould infections (IMIs). OBJECTIVE: To investigate the safety and usefulness of FB in IMI. We evaluate the factors associated with a successful diagnosis of IMI using FB. Further, we compare subjects of invasive pulmonary aspergillosis (IPA) with pulmonary mucormycosis (PM). METHODS: We retrospectively reviewed the clinical features, imaging data, bronchoscopy, microbiology and pathology details of subjects who underwent FB for suspected IMI. We categorised FB as diagnostic if it contributed to the diagnosis of IMI. We performed a multivariate analysis to identify the factors associated with a diagnostic bronchoscopy. RESULTS: Of the 3521 FB performed over 18 months, 132 (3.7%) were done for suspected IMIs. We included 107 subjects for the final analysis. The risk factors for IMI included renal transplantation (29.0%), diabetes (27.1%), haematological malignancy (10.3%) and others. We found bronchoscopic abnormalities in 33 (30.8%) subjects, and these were more frequent in those with confirmed PM (67%) than IPA (27%). IMI was confirmed in 79 (14 proven, 48 probable and 17 possible) subjects. FB was diagnostic in 71%. We experienced major complications in three cases (2.7%), including one death. On multivariate analysis, the visualisation of endobronchial abnormalities during FB (OR [95%, CI], 8.5 [1.4-50.4]) was the only factor associated with a diagnostic FB after adjusting for age and various risk factors. CONCLUSIONS: Flexible bronchoscopy is a useful and safe procedure in diagnosing IMIs. The presence of endobronchial abnormalities predicts a successful diagnostic yield on FB.

Incidence, predisposing conditions and outcomes of cutaneous mucormycosis: A national database study.

BACKGROUND: The body of evidence on cutaneous mucormycosis is largely derived from case reports or single-centre databases. OBJECTIVES: Our study aimed to describe incidence, predisposing factors and inpatient outcomes of cutaneous mucormycosis in the United States. METHODS: We conducted a population-based retrospective study using the National Inpatient Sample 2016-17 data. Fifty-six discharges had a diagnosis of cutaneous mucormycosis on the International Classification of Diseases, tenth revision. Descriptive analysis was performed for the demographics, predisposing factors, length of stay (LOS), cost and inpatient mortality. The NIS represents 20% of all discharges in the United States, which allowed us to estimate the national incidence of cutaneous mucormycosis. RESULTS: An estimated total of 280 admissions occurred between 2016 and 2017, indicating 3.9 cases per million admissions across the United States. The estimated incidence rate was 0.43 cases per million people per year. Median age was 49.5 (19-59) years, 44.6% were female, and 54.9% were Caucasian. We identified haematologic malignancies (48.2%) and solid organ transplantations (10.7%), often accompanied by skin/soft tissue or post-procedural infections, were the most common predisposing conditions. Median LOS was 15 (6-31) days, median total charges were 187,030 (65,962-446,265) USD, and in-hospital mortality rate was 16.1%. CONCLUSIONS: In current clinical practice, physicians may encounter cutaneous mucormycosis most commonly in severely immunocompromised hosts with haematologic malignancies or transplantations, accompanied by skin/soft tissue or post-procedural infections. A high index of suspicion and prompt tissue sampling in at-risk groups is important to improve the outcomes.

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.

An Infant with Acute Bloody Diarrhea and Gastrointestinal Basidiobolomycosis: An Unusual Presentation of a Rare Disease.

Basidiobolomycosis is a fungal infection caused mainly by Basidiobolus ranarum, a filamentous fungus of the order Entomophthorales and the family Basidiobolaceae. This infection typically involves the skin and soft tissue; however, visceral organ involvement has also been reported. Here, we report a case of gastrointestinal basidiobolomycosis in a young child who presented with acute bloody diarrhea which was initially misdiagnosed as intussusception.

Coronavirus Disease (Covid-19) Associated Mucormycosis (CAM): Case Report and Systematic Review of Literature.

Severe coronavirus disease (COVID-19) is currently managed with systemic glucocorticoids. Opportunistic fungal infections are of concern in such patients. While COVID-19 associated pulmonary aspergillosis is increasingly recognized, mucormycosis is rare. We describe a case of probable pulmonary mucormycosis in a 55-year-old man with diabetes, end-stage kidney disease, and COVID-19. The index case was diagnosed with pulmonary mucormycosis 21 days following admission for severe COVID-19. He received 5 g of liposomal amphotericin B and was discharged after 54 days from the hospital. We also performed a systematic review of the literature and identified seven additional cases of COVID-19 associated mucormycosis (CAM). Of the eight cases included in our review, diabetes mellitus was the most common risk factor. Three subjects had no risk factor other than glucocorticoids for COVID-19. Mucormycosis usually developed 10-14 days after hospitalization. All except the index case died. In two subjects, CAM was diagnosed postmortem. Mucormycosis is an uncommon but serious infection that complicates the course of severe COVID-19. Subjects with diabetes mellitus and multiple risk factors may be at a higher risk for developing mucormycosis. Concurrent glucocorticoid therapy probably heightens the risk of mucormycosis. A high index of suspicion and aggressive management is required to improve outcomes.

Fatal necrotising cutaneous mucormycosis due to novel Saksenaea species: a case study.

This case report describes the progressive wound infection in the left thigh of a 34-year-old man due to an old landmine explosion. The infection developed into rapidly spreading skin and soft tissue necrotising Saksenaea infection, despite antifungal therapy and surgical debridement. The report provides evidence that Saksenaea spp. should be added to the list of mucoralean fungi that can cause severe necrotising infection. It also highlights the need for improved early diagnostic procedures and enhanced understanding of Saksenaea virulence factors that contribute to necrotising infection.