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.

The Comparative Evaluation of the Fujifilm Wako ß-Glucan Assay and Fungitell Assay for Diagnosing Invasive Fungal Disease.

Serum 1,3-ß-d-glucan(BDG) is a broad fungal biomarker for invasive fungal disease (IFD). More data is still required to support the Fujifilm Wako assay as a valuable alternative to the widely used Fungitell assay. We included archived serum samples from 157 individuals (97 cases; 33-IA, 64-IC, and 60 controls) for the comparative performance evaluation of the Fungitell assay and the Fujifilm Wako assay for IFD diagnosis. The BDG value was significantly higher in patients with IFD vs. controls (70.79 pg/mL vs. 3.03 pg/mL, p: 0.0002). An area under the curve (AUC) for the IFD, IC, and IA diagnosis was 0.895, 0.910, and 0.866, respectively, for the Fujifilm Wako assay. Based on the highest Youden's index (0.667), a cutoff of 5 pg/mL was selected as the optimum for the Fujifilm Wako assay with good sensitivity (79.4%), specificity (88.3%) and agreement (84.7%, Cohen's k:0.691) with the Fungitell assay. The mean run-time of the Fujifilm Wako assay was 70.12 min, and real-time observation allowed earlier time to result in Fujifilm Wako vs. Fungitell assay (37 vs. 120 min, p: < 0.0001). Thus, our findings support the diagnostic value of the Fujifilm Wako assay for the diagnosis of IFD. However, there is still a need to validate diagnostic protocols to optimize their use in multi-centre studies with different patient groups.

Evaluation of environmental Mucorales contamination in and around the residence of COVID-19-associated mucormycosis patients.

Introduction: Recently, India witnessed an unprecedented surge of coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) cases. In addition to patient management issues, environmental Mucorales contamination possibly contributed to the outbreak. A recent study evaluated environment contamination by Mucorales in the hospital setting. However, a considerable number of CAM patients were never admitted to a hospital before the development of the disease. The present study, therefore, planned to evaluate Mucorales contamination of patients' residences. Methods: The residential environment of 25 patients with CAM living in north India was surveyed. Air samples were collected from indoor and immediate outdoor vicinity of the patients' residence and cultured on Dichloran Rose-Bengal Chloramphenicol (DRBC) agar with benomyl for selective isolation of Mucorales. Surface swab samples were also collected from the air coolers fitted in those residences and cultured on DRBC agar. The isolates were identified by phenotypic and genotypic methods. Amplified fragment length polymorphism (AFLP) was employed to evaluate the genetic relatedness of the environmental and patients' clinical isolates. Results: The median spore count (mean ± SD, cfu/m3) of Mucorales in the air of patients' bedrooms was significantly higher than in the air in other rooms in those residences (3.55 versus 1.5, p = 0.003) or the air collected directly from the front of the air cooler (p < 0.0001). The Mucorales spore count in the environment did not correlate with either ventilation of the room or hygiene level of the patients' residences. Rhizopus arrhizus was isolated from the environment of all patients' residences (n = 25); other Mucorales species isolated were Cunninghamella bertholletiae (n = 14), Rhizopus microsporus (n = 6), Rhizopus delemar (n = 6), Syncephalastrum racemosum (n = 1), Lichtheimia corymbifera (n = 1), and Mucor racemosus (n = 1). Genetic relatedness was observed between 11 environmental isolates from the patients' bedrooms and respective clinical isolates from patients. Discussion: The study supported the view that the patients might have acquired Mucorales from the home environment during the post-COVID-19 convalescence period. Universal masking at home during patients' convalescence period and environmental decontamination could minimize exposure in those susceptible patients.

Epidemiology of Invasive Fungal Infections in Solid Organ Transplant Recipients: an Indian Perspective.

Purpose of Review: This review summarizes the available Indian data on epidemiology of invasive fungal infections (IFI) in recipients of solid organ transplants (SOT). The epidemiology is further compared with studies from other parts of the world for each SOT type. Recent Findings: The available studies on Indian epidemiology of IFI in SOT are scarce, though the number of SOTs performed in India have increased tremendously in recent years. The limited data from India present a distinct spectrum of infection in transplant recipients with high incidence of mucormycosis. During COVID-19 outbreak, IFI rate increased and renal transplant recipients acquired mucormycosis earlier than previous studies. Summary: Maximum data on IFI was available from renal transplant recipients, wherein mucormycosis was the predominant IFI in Indian patients in contrast to invasive candidiasis in majority countries. The other IFIs had varied spectrum. With the increasing number of SOTs being performed and the already persisting high burden of IFI in India, there is an urgent need of larger prospective studies on epidemiology of IFI in transplant recipients.

Evaluation of environmental Mucorales contamination in and around the residence of COVID-19-associated mucormycosis patients

Introduction Recently, India witnessed an unprecedented surge of coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) cases. In addition to patient management issues, environmental Mucorales contamination possibly contributed to the outbreak. A recent study evaluated environment contamination by Mucorales in the hospital setting. However, a considerable number of CAM patients were never admitted to a hospital before the development of the disease. The present study, therefore, planned to evaluate Mucorales contamination of patients’ residences. Methods The residential environment of 25 patients with CAM living in north India was surveyed. Air samples were collected from indoor and immediate outdoor vicinity of the patients’ residence and cultured on Dichloran Rose–Bengal Chloramphenicol (DRBC) agar with benomyl for selective isolation of Mucorales. Surface swab samples were also collected from the air coolers fitted in those residences and cultured on DRBC agar. The isolates were identified by phenotypic and genotypic methods. Amplified fragment length polymorphism (AFLP) was employed to evaluate the genetic relatedness of the environmental and patients’ clinical isolates. Results The median spore count (mean ± SD, cfu/m3) of Mucorales in the air of patients’ bedrooms was significantly higher than in the air in other rooms in those residences (3.55 versus 1.5, p = 0.003) or the air collected directly from the front of the air cooler (p < 0.0001). The Mucorales spore count in the environment did not correlate with either ventilation of the room or hygiene level of the patients’ residences. Rhizopus arrhizus was isolated from the environment of all patients’ residences (n = 25);other Mucorales species isolated were Cunninghamella bertholletiae (n = 14), Rhizopus microsporus (n = 6), Rhizopus delemar (n = 6), Syncephalastrum racemosum (n = 1), Lichtheimia corymbifera (n = 1), and Mucor racemosus (n = 1). Genetic relatedness was observed between 11 environmental isolates from the patients’ bedrooms and respective clinical isolates from patients. Discussion The study supported the view that the patients might have acquired Mucorales from the home environment during the post-COVID-19 convalescence period. Universal masking at home during patients’ convalescence period and environmental decontamination could minimize exposure in those susceptible patients.

Cirrhosis and fungal infections-a cocktail for catastrophe: A systematic review and meta-analysis with machine learning.

OBJECTIVES: We evaluated the magnitude and factors contributing to poor outcomes among cirrhosis patients with fungal infections (FIs). METHODS: We searched PubMed, Embase, Ovid and WOS and included articles reporting mortality in cirrhosis with FIs. We pooled the point and relative-risk (RR) estimates of mortality on random-effects meta-analysis and explored their heterogeneity (I 2 ) on subgroups, meta-regression and machine learning (ML). We assessed the study quality through New-Castle-Ottawa Scale and estimate-asymmetry through Eggers regression. (CRD42019142782). RESULTS: Of 4345, 34 studies (2134 patients) were included (good/fair/poor quality: 12/21/1). Pooled mortality of FIs was 64.1% (95% CI: 55.4-72.0, I 2 : 87%, p < .01), which was 2.1 times higher than controls (95% CI: 1.8-2.5, I 2 :89%, p < .01). Higher CTP (MD: +0.52, 95% CI: 0.27-0.77), MELD (MD: +2.75, 95% CI: 1.21-4.28), organ failures and increased hospital stay (30 vs. 19 days) were reported among cases with FIs. Patients with ACLF (76.6%, RR: 2.3) and ICU-admission (70.4%, RR: 1.6) had the highest mortality. The risk was maximum for pulmonary FIs (79.4%, RR: 1.8), followed by peritoneal FIs (68.3%, RR: 1.7) and fungemia (55%, RR: 1.7). The mortality was higher in FIs than in bacterial (RR: 1.7) or no infections (RR: 2.9). Estimate asymmetry was evident (p < 0.05). Up to 8 clusters and 5 outlier studies were identified on ML, and the estimate-heterogeneity was eliminated by excluding such studies. CONCLUSIONS: A substantially worse prognosis, poorer than bacterial infections in cirrhosis patients with FIs, indicates an unmet need for improving fungal diagnostics and therapeutics in this population. ACLF and ICU admission should be included in the host criteria for defining IFIs.

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. Supplementary Information The online version contains supplementary material available at 10.1007/s11046-022-00645-6.

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.

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.

Definition, diagnosis, and management of COVID-19-associated pulmonary mucormycosis: Delphi consensus statement from the Fungal Infection Study Forum and Academy of Pulmonary Sciences, India.

COVID-19-associated pulmonary mucormycosis (CAPM) remains an underdiagnosed entity. Using a modified Delphi method, we have formulated a consensus statement for the diagnosis and management of CAPM. We selected 26 experts from various disciplines who are involved in managing CAPM. Three rounds of the Delphi process were held to reach consensus (≥70% agreement or disagreement) or dissensus. A consensus was achieved for 84 of the 89 statements. Pulmonary mucormycosis occurring within 3 months of COVID-19 diagnosis was labelled CAPM and classified further as proven, probable, and possible. We recommend flexible bronchoscopy to enable early diagnosis. The experts proposed definitions to categorise dual infections with aspergillosis and mucormycosis in patients with COVID-19. We recommend liposomal amphotericin B (5 mg/kg per day) and early surgery as central to the management of mucormycosis in patients with COVID-19. We recommend response assessment at 4-6 weeks using clinical and imaging parameters. Posaconazole or isavuconazole was recommended as maintenance therapy following initial response, but no consensus was reached for the duration of treatment. In patients with stable or progressive disease, the experts recommended salvage therapy with posaconazole or isavuconazole. CAPM is a rare but under-reported complication of COVID-19. Although we have proposed recommendations for defining, diagnosing, and managing CAPM, more extensive research is required.

As the virus sowed, the fungus reaped! A comparative analysis of the clinico-epidemiological characteristics of rhino-orbital mucormycosis before and during COVID-19 pandemic.

BACKGROUND: The sudden surge of mucormycosis cases which happened during the second wave of COVID-19 pandemic was a significant public health problem in India. OBJECTIVES: The aim of this study was to analyse the clinico-epidemicological characteristics of the mucormycosis cases to determine the changes that had occurred due to COVID-19 pandemic. METHODOLOGY: A retrospective cross-sectional study was conducted at the Department of Otolaryngology Head and Neck Surgery, PGIMER, Chandigarh, India. Patients diagnosed with rhino-orbital mucormycosis were categorised into the following groups: Pre-pandemic(May 2019 to April 2020), Pandemic Pre-epidemic (May 2020 to April 2021) and Epidemic (1 May 2021 to 12 July 2021). The epidemiological, clinical and surgical data of all the patients were retrieved from the hospital records and analysed. RESULTS: The epidemic period had 370 cases, compared with 65 during pandemic period and 42 in the pre-pandemic period. Diabetes mellitus was seen in 87% of cases during epidemic period, 92.9% in the pre-pandemic period and 90.8% in the pre-pandemic pre-epidemic period. The proportion of patients suffering from vision loss, restricted extra-ocular movements, palatal ulcer and nasal obstruction was higher in the pre-epidemic groups, and the difference was significant (p, <.01). There was no history of oxygen use in 85.9% of patients and no steroid use in 76.5%. The death rates were the lowest during epidemic (10%). CONCLUSION: COVID-19 has caused a statistically significant increase in the number of mucormycosis infections. The mortality and morbidity which showed an increase during the first wave of COVID-19 decreased significantly during the epidemic period.

Pulmonary Artery Pseudoaneurysm in COVID-19-Associated Pulmonary Mucormycosis: Case Series and Systematic Review of the Literature.

Literature on COVID-19-associated pulmonary mucormycosis (CAPM) is sparse. Pulmonary artery pseudoaneurysm (PAP) is an uncommon complication of pulmonary mucormycosis (PM), and rarely reported in CAPM. Herein, we report five cases of CAPM with PAP managed at our center and perform a systematic review of the literature. We diagnosed PM in those with clinico-radiological suspicion and confirmed it by microbiology or histopathology. We encountered five cases of CAPM with PAP (size ranged from 1 × 0.8 cm to ~ 4.9 × 4.8 cm). All subjects had diabetes and were aged 55-62 years (75% men). In two cases, COVID-19 and mucormycosis were diagnosed simultaneously, while in three others, COVID-19 preceded PM. One subject who underwent surgery survived, while all others died (80% mortality). From our systematic review, we identified one additional case of CAPM with PAP in a transplant recipient. CAPM with PAP is rare with high mortality. Early diagnosis and multimodality management are imperative to improve outcomes.

Therapeutic drug monitoring of posaconazole delayed release tablet while managing COVID-19-associated mucormycosis in a real-life setting.

BACKGROUND: Along with COVID-19 pandemic, India has faced an outbreak of COVID-19-associated mucormycosis (CAM). Due to restricted availability of amphotericin B during this outbreak, clinicians were forced to use posaconazole or isavuconazole preparations as first-line or alternate therapy in many patients. We planned an early monitoring of posaconazole trough level while using delayed release (DR) tablet as first-line or alternate therapy. OBJECTIVES: Primary objective of the study was to determine percentage of patients achieving arbitrarily decided therapeutic posaconazole levels (≥1.2 µg/ml) after using standard dosages of posaconazole. Secondary objective was to identify potential factors associated with sub-therapeutic posaconazole levels. METHODS: We performed retrospective chart review of the hospitalised patients, who received posaconazole DR tablet as first-line or alternate therapy to treat CAM during outbreak period (March 1 to May 31, 2021). High-performance liquid chromatographic (HPLC) method was used to measure trough level of posaconazole. RESULTS: Posaconazole serum levels of 29 patients were analysed, who received posaconazole DR tablet. Majority (n = 23) were male with the median (range) age 53 (24-86) years. The mean (SD) posaconazole level was 1.66 (0.76) µg/ml. Sub-therapeutic posaconazole trough level was observed in 7 (24.1%) patients. Relatively younger patients were associated with lower posaconazole level (p = .046). Except two patients, all the patients tolerated posaconazole well. CONCLUSIONS: The study supports the posaconazole trough level measurement on day 4 while using posaconazole DR tablet as first-line or alternate therapy to treat mucormycosis during limited supply of amphotericin B.

Infection control in the intensive care unit: expert consensus statements for SARS-CoV-2 using a Delphi method.

During the current COVID-19 pandemic, health-care workers and uninfected patients in intensive care units (ICUs) are at risk of being infected with SARS-CoV-2 as a result of transmission from infected patients and health-care workers. In the absence of high-quality evidence on the transmission of SARS-CoV-2, clinical practice of infection control and prevention in ICUs varies widely. Using a Delphi process, international experts in intensive care, infectious diseases, and infection control developed consensus statements on infection control for SARS-CoV-2 in an ICU. Consensus was achieved for 31 (94%) of 33 statements, from which 25 clinical practice statements were issued. These statements include guidance on ICU design and engineering, health-care worker safety, visiting policy, personal protective equipment, patients and procedures, disinfection, and sterilisation. Consensus was not reached on optimal return to work criteria for health-care workers who were infected with SARS-CoV-2 or the acceptable disinfection strategy for heat-sensitive instruments used for airway management of patients with SARS-CoV-2 infection. Well designed studies are needed to assess the effects of these practice statements and address the remaining uncertainties.

Serum iron indices in COVID-19-associated mucormycosis: A case-control study.

BACKGROUND: Whether dysregulated iron metabolism is associated with COVID-19-associated mucormycosis (CAM) remains unknown. Herein, we compare the serum iron indices in COVID-19 subjects with and without mucormycosis. METHODS: We conducted a case-control study enrolling COVID-19 participants with and without mucormycosis. We compared the baseline serum iron indices (iron, ferritin, total iron-binding capacity [TIBC], unsaturated iron-binding capacity and percentage transferrin saturation) between CAM cases and COVID-19 controls. Additionally, we performed a multivariate logistic regression analysis to assess whether any iron indices are associated with CAM. RESULTS: We enrolled 28 CAM cases (mean age 53.6 years old; 78.6% men) and 26 controls (mean age 57.2 years old; 73.1% men). Rhino-orbital (±cerebral) mucormycosis (85.7%) was the most clinical presentation. Diabetes mellitus was more frequent in the cases than controls (75% vs. 42.3%; p = .015). Hypoxaemia during COVID-19 illness was more common in controls than cases. The mean serum iron values (33 vs. 45 µg/dl, p = .03) and TIBC (166.6 vs. 201.6 µg/dl, p = .003) were significantly lower in CAM cases than controls. On multivariate analysis, we found a lower TIBC (odds ratio [OR] 0.97; 95% confidence interval [CI], 0.95-0.99) and diabetes mellitus (OR 5.23; 95% CI, 1.21-22.68) to be independently associated with CAM after adjusting for serum iron, ferritin and glucocorticoid therapy. The case fatality rate of CAM was 73.9%. The iron indices were not significantly different between CAM survivors and non-survivors. CONCLUSIONS: The CAM is associated with lower TIBC levels than COVID-19 subjects without mucormycosis, suggesting dysregulated iron metabolism in its pathogenesis. Further studies are required to confirm our preliminary observations.

Multicenter Epidemiologic Study of Coronavirus Disease-Associated Mucormycosis, India.

During September-December 2020, we conducted a multicenter retrospective study across India to evaluate epidemiology and outcomes among cases of coronavirus disease (COVID-19)-associated mucormycosis (CAM). Among 287 mucormycosis patients, 187 (65.2%) had CAM; CAM prevalence was 0.27% among hospitalized COVID-19 patients. We noted a 2.1-fold rise in mucormycosis during the study period compared with September-December 2019. Uncontrolled diabetes mellitus was the most common underlying disease among CAM and non-CAM patients. COVID-19 was the only underlying disease in 32.6% of CAM patients. COVID-19-related hypoxemia and improper glucocorticoid use independently were associated with CAM. The mucormycosis case-fatality rate at 12 weeks was 45.7% but was similar for CAM and non-CAM patients. Age, rhino-orbital-cerebral involvement, and intensive care unit admission were associated with increased mortality rates; sequential antifungal drug treatment improved mucormycosis survival. The COVID-19 pandemic has led to increases in mucormycosis in India, partly from inappropriate glucocorticoid use.

Epidemiology and Pathophysiology of COVID-19-Associated Mucormycosis: India Versus the Rest of the World.

The coronavirus disease 2019 (COVID-19) pandemic has led to a concerning resurgence of mucormycosis. More than 47,000 cases of mucormycosis were reported in three months from India. We update our systematic review on COVID-19-associated mucormycosis (CAM) till June 21st, 2021, comparing cases reported from India and elsewhere. We included individual patient details of 275 cases of CAM, of which 233 were reported from India and 42 from the rest of the world. Diabetes mellitus was the most common underlying risk factor for CAM in India than in other countries. The fatality rate of cases reported from India (36.5%) was less than the globally reported cases (61.9%), probably due to the predominance of rhino-orbital mucormycosis. On a multivariate analysis, we found that pulmonary or disseminated mucormycosis cases and admission to the intensive care unit were associated with increased mortality, while combination medical therapy improved survival. The paucity of pulmonary and disseminated mucormycosis cases from India suggests that these cases were either not diagnosed or reported, further supported by a trend of search data from the Google search engine. In this review, we discuss the factors explaining the substantial rise in cases of CAM. We also propose a hypothetical model describing the epidemiologic triad of CAM.