Metagenomic insights into fungal community composition of the nasopharyngeal region of COVID-19 associated mucormycosis patients from India.

Coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM) was reported predominantly from India during the second wave of COVID-19  and has a high mortality rate. The present study aims to understand the fungal community composition of the nasopharyngeal region of CAM-infected individuals and compare it with severe COVID-19 patients and healthy controls. The fungal community composition was decoded by analyzing the sequence homology of the internal transcribed spacer-2-(ITS-2) region of metagenomic DNA extracted from the upper respiratory samples. The alpha-diversity indices were found to be significantly altered in CAM patients (p < 0.05). Interestingly, a higher abundance of Candida africana, Candida haemuloni, Starmerella floris, and Starmerella lactiscondensi was observed exclusively in CAM patients. The interindividual changes in mycobiome composition were well supported by beta-diversity analysis (p < 0.05). The current study provides insights into the dysbiosis of the nasal mycobiome during CAM infection. In conclusion, our study shows that severe COVID-19 and CAM are associated with alteration in mycobiome as compared to healthy controls. However, the sequential alteration in the fungal flora which ultimately leads to the development of CAM needs to be addressed by future studies.

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

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

Is mucormycosis the end? A comprehensive management of orbit in COVID associated rhino-orbital-cerebral mucormycosis: preserving the salvageable.

BACKGROUND: Rhino-orbital-cerebral mucor mycosis (ROCM) is a relatively rare opportunistic infection caused by the Mucorales species. While ROCM suggests involvement of the paranasal sinuses, orbit and brain ROM (rhino-orbital-Mucormycosis) stands for the fungal invasion in sinuses and orbit sans cerebral involvement. In India with the outbreak of the second COVID wave and the delta variant of the virus, there has been a steep increase in this opportunistic fulminant fungal infection, named COVID-associated Mucor mycosis (CAM). The most critical question in orbital management is when to go ahead with an exenteration. Our study aims to design a pertinent minimal invasive surgical protocol for surgeons to manage such cases based on our surgical experience and mitigate the need for exenteration and save the eyes wherever possible. METHODS: The study is a retrospective analysis of patients of ROM with and without brain involvement, who underwent minimal surgical management between March 2021 to March 2022 along with their follow-up. RESULTS: There were 184 eyes of 148 patients diagnosed with CAM. The mean age was 51.7 years with a male predominance of 103 (70%). All patients developed ROM following the COVID-19 infection and the duration between diagnosis of COVID-19 and ROM was 36 ± 23 days. 18 cases (12%) were bilateral. 76 eyes (41%) had no vision at the presentation. Imaging revealed paranasal sinus involvement (100%), orbital apex involvement (61%), cavernous sinus involvement (53%), and central nervous system (CNS) involvement (47%). All the patients (100%) were treated with systemic Liposomal amphotericin-B and sinus debridement. Endoscopic debridement of the orbital disease was performed in 45 (30.4%) cases, 15(8.1%) eyes underwent exenteration and were later rehabilitated with a customized ocular prosthesis, 103 (56%) eyes underwent transcutaneous retrobulbar amphotericin-B. At a mean follow-up of 13.1 months; the complete resolution was seen in 25 (17%) cases, the residual stable lesion was seen in 77(52%) of the cases and new lesions were developed in 13(9%) of the cases. Mortality was seen in 33 (22%) patients and all of them had CNS involvement. CONCLUSIONS: Systemic and protocol-based management can save the life and salvage the eyes.

A comparative study on the clinical profile of COVID-related and non-COVID-related acute invasive fungal rhino sinusitis.

PURPOSE: To compare the clinical profile of COVID-related and non-COVID-related rhino-orbito-cerebral invasive fungal disease. METHODS: We have compared the comorbidities, clinical features, course of the disease and outcome between COVID-related and non-COVID-related acute invasive fungal rhinosinusitis (AIFRS) of the rhino-orbito-cerebral form. RESULTS: HbA1c and blood sugar at the time of admission were significantly higher in the non-COVID group (P < 0.05). Duration of stay, and use of steroids were significantly higher among the COVID group (P < 0.05). The period of hospital stay was significantly higher in the COVID group. The overall survival in the COVID group was 67.57%. In the non-COVID group the overall survival was 61.90%.This study found that odds of surgical treatment was significantly lower among non-survivors (P < 0.05). Similarly patients who developed stages 3 & 4 of the disease had a lower survival rate (P < 0.05). CONCLUSION: Diabetes mellitus is a key risk factor for the development of AIFRS. Pre-existing, grossly uncontrolled DM was the predisposing factor in the non-COVID group. Deranged glucose profile associated with COVID illness and its treatment and immunological disturbances in a vulnerable population, contributed to the surge in cases of AIFRS in the COVID-19-related group. Patients who underwent combined medical and surgical treatment had a significantly better outcome following AIFRS.

An interesting report of COVID-19 associated mucormycosis (CAM) cases by two different species of Mucorales.

During surge of COVID-19-associated mucormycosis (CAM), we identified five cases of CAM where two different species of Mucorales were isolated. All had history of diabetes mellitus and presented with clinical features suggesting rhino-orbital mucormycosis. The patients grew different species from their nasal scraping/biopsy samples, Rhizopus arrhizus, R. homothallicus (n = 2); R. homothallicus, Lictheimia corymbifera (n = 1); R. arrhizus, Mucor spp (n = 1); and L. corymbifera, Apophysomyces variabilis (n = 1). All patients underwent surgical and medical (liposomal amphotericin B) treatment. All, except one growing A. variabilis and L. corymbifera survived. Mixed infection by more than one Mucorales in CAM is unique and warrants epidemiological investigation.

Observational study on the clinical profile and treatment outcome on long-term follow-up of COVID-19 associated mucormycosis.

MATERIALS AND METHODS: Patients diagnosed with COVID-19 associated mucormycosis were followed up for 6 months to study the clinical profile, readmissions, long-term treatment outcome and the mortality rate. RESULTS: Among 37 patients with COVID-19 associated mucormycosis, the mortality rate was 33.3 %, 42.9% and 100 % among patients with mild, moderate and severe COVID-19 infection. One month after discharge, among the 20 patients who survived, 10 (50 %) patients had worsening symptoms and required readmission. Nine patients required readmission for amphotericin and 1 patient was admitted for surgical intervention. On follow-up at 1 month, 30 % (6/20) patients became asymptomatic. However, at 3 months, 45 % (9/20) of the patients were asymptomatic. At 6 months of follow-up, 80 % (16/20) were asymptomatic. At 6 months, one each had residual abnormalities like visual loss in one eye, visual field deficit, change in voice and residual weakness of the limbs along with cranial nerve paresis. CONCLUSION: The follow-up study revealed that a significant number of patients required readmission within the first month, but most of the patients became asymptomatic by 6 months. The readmission rate was higher in patients who received a shorter duration of amphotericin.

Incidence of COVID-19-Associated Mucormycosis in COVID-19 Patients after Discharge from the COVID-19 Hospital.

Background: There are studies available on the prevalence of coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) in hospitalized patients but not on the incidence of CAM in post-discharge patients. The aim of our study was to find the incidence of CAM in the patients discharged from a COVID hospital. Material and Methods: Adult patients with COVID discharged between March 1, 2021 and June 30, 2021 were contacted and enquired about sign and symptoms of CAM. Data of all included patients were collected from electronic records. Results: A total of 850 patients responded, among which 59.4% were males, 66.4% patients had co-morbidities, and 24.2% had diabetes mellitus. Around 73% of patients had moderate to severe disease and were given steroids; however, only two patients developed CAM post discharge. Conclusion: The incidence of CAM post discharge was low in our study, which could be attributed to protocolized therapy and intensive monitoring.

Central Retinal Artery Occlusion in COVID-Associated Mucormycosis.

Introduction: Significant surge of mucormycosis was reported in the Indian Subcontinent during the second wave of the COVID-19 pandemic. COVID-associated mucormycosis (CAM) was defined as the development of features of mucormycosis with prior or current history of COVID-19 infection. Rapid angioinvasion is an important characteristic of mucormycosis. Authors intended to find out the prevalence of retinal arterial occlusion and its association with vascular embolic occlusion elsewhere in the body among CAM patients in this study. Methods: This was an observational study. All consecutive-confirmed cases of mucormycosis (n = 89) and age-/gender-/risk factor-matched controls (n = 324) admitted in the designated COVID center were included in the study. All cases and controls underwent comprehensive ophthalmological, otorhinological, and neurological examinations. All necessary investigations to support the clinical diagnosis were done. Qualitative data were analyzed using the Chi-square test. Quantitative data for comparison of means between the cases and controls were done using unpaired t-test. Results: Twenty-one (23.59%) patients manifested the defined outcome of central retinal artery occlusion (CRAO). Among age-matched control, with similar diabetic status, none had developed the final outcome as defined (P < 0.05). About 90.47% of subjects with CRAO presented with no perception of light vision. Thirteen subjects (61.9%) with the final outcome developed clinical manifestations of stroke during the course of their illness with radiological evidence of watershed infarction (P = 0.001). Orbital debridement was performed in 9 (42.85%) subjects while orbital exenteration was done in 8 (38.09%) subjects. Conclusions: CRAO in CAM patients was found to have aggressive nature turning the eye blind in a very short period of time. CRAO can serve as a harbinger for subsequent development of more debilitating and life-threatening conditions such as stroke among CAM patients.

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.

Risk Factors, Clinical Manifestations, and Outcomes of COVID-19-Associated Mucormycosis and Other Opportunistic Fungal Infections.

INTRODUCTION: An epidemic of opportunistic fungal infections during the second wave of the coronavirus disease 2019 (COVID-19) pandemic badly affected India in 2021. Several unknown, unique factors played a role in its causation and survival outcomes, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The purpose of this study was to analyse the probable underlying risk factors and to know immediate and late outcomes of opportunistic fungal infections in the unique setting of the SARS-CoV-2 pandemic. METHODS: In this retrospective cohort study, clinical records of COVID-19-associated opportunistic fungal infections were reviewed for risk factors, clinical features, microbiological and pathological findings, and outcomes during a one-year follow-up at a tertiary care teaching hospital in Northern India. RESULTS: A total of 390 patients were admitted with symptoms and clinical signs consistent with the criteria for the diagnosis of COVID-19-associated mucormycosis (CAM). Diabetes mellitus was the most common comorbidity (74%). During the management of SARS-CoV-2, 192 (49%) patients received corticosteroids, 151 (39%) were on oxygen support, and 143 (37%) used at-home steam inhalation. Masks of any type were used by 236 (60.5%) patients, of whom most used cloth masks (n=147, 37.6%). Microbiologically, fungal growth was positive in 138 (35.3%) samples; of these, 74 (19%) had non-Mucorales fungal colonies. The fungal infection invaded structures beyond the paranasal sinuses in 60% of the cases. The overall mortality in this cohort after one-year follow-up was 40.25%. CONCLUSIONS: An alignment of several predisposing conditions precipitated an epidemic of opportunistic fungal infections during the COVID-19 pandemic that resulted in high mortality in affected patients.

Epidemiology, Clinical Profile, and Analysis of Risk Factors in COVID Associated Rhino-orbito-cerebral Mucormycosis Patients - An Observational Study.

Aim of Study: To study the clinico-epidemiological profile and identify risk factors for the development of COVID-19-associated mucormycosis (CAM) among the patients treated at our regional mucormycosis center. Materials and Methods: This was a cross-sectional single-centre observational study. All CAM patients admitted to Government Rajaji Hospital, Madurai from April 2021- August 2021 were included in the study. Information regarding clinical features, potential risk factors, diagnostic workup, and comorbid illness was collected. Results: A total of 164 patients of CAM were admitted to our hospital with a mean age of 51.7 years. Out of 164 patients, 12 patients were not covid positive, based on imaging and RT-PCR, however subclinical infection could not be ruled out. Out of the 164 patients studied, 160 patients had diabetes, out of which 66% (n = 105) patients had a previous history of diabetes, and 34% (n = 55) had newly detected diabetes. Most of the patients admitted with mucormycosis had uncontrolled diabetes (94%) and were not on insulin therapy, but were on oral antidiabetic drugs alone. The majority of the patients (68%) have received steroids (IV/oral) during the COVID-19 illness. 74% of these patients were under hospitalization for COVID-19 disease. Only 30% (n = 50) of CAM patients had a history of oxygen therapy and 7% of these patients were treated in ICU during active COVID-19 illness. 59% of patients used cloth masks without adequate hygiene, rest 41% (n = 67) patients reused disposable masks. We also found that 87% of the patients developing mucormycosis had exposure to organic material in the convalescence period of COVID-19 illness. Conclusions: From our study, we found steroid use, poorly controlled diabetes mellitus, reuse of masks, daily steam inhalation, and exposure to organic matter to be more associated with CAM, but oxygen therapy was less associated with CAM. Hence, we could suggest screening for hyperglycemia and daily use of disposable surgical masks to be continued for at least 4 weeks post-COVID-19. It is preferable to continue insulin in titrated doses along with OHA for at least 4 weeks following steroid cessation in the post-COVID-19 period as there is are considerably increased inflammatory cytokine levels in the convalescence phase. Clean environmental hygiene would also help prevent CAM.

Neem and Turmeric in the management of Covid Associated Mucormycosis (CAM) derived through network pharmacology.

Mucormycosis or 'Black Fungus' has been known to target immunocompromised individuals even before the emergence of COVID-19. Nevertheless, the present circumstances provide the best opening for Covid Associated Mucormycosis (CAM), as the global pandemic is engulfing a large part of human population making them immunocompromised. This drastic increase in Mucormycosis infections has to be addressed as early as possible. There is a growing tendency of relying upon herbal drugs that have minimal side effects and does not compromise our immune system. Recently, the concept of network pharmacology has grabbed the attention of modern science, especially advanced medical sciences. This is a new discipline that can use computational power to systematically catalogue the molecular interactions between botanical formulations and the human body. In this study, Neem and Turmeric was considered as the target plants and an attempt was made to reveal various aspects through which phytocompounds derived from them may effectively manage CAM menace. We have taken a step-by-step approach for identifying the target proteins and ligands associated with Mucormycosis treatment. Functional network analysis and Molecular docking approaches were applied to validate our findings. Quercetin derived from both Neem and Turmeric was found to be one of the main phytocompounds working against Mucormycosis. Along with that, Caffeic acid, Curcumin, Kaempferol, Tetrahydrocurcumin and Myricetin also play a pivotal role in fighting against Black-Fungus. A thorough analysis of our result suggested a triple-front attack on the fungal pathogens and the approaches are necrosis inhibition, iron chelation and immuno-boosting.Communicated by Ramaswamy H. Sarma.

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

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

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

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

COVID-19-Associated Pulmonary Fungal Infection among Pediatric Cancer Patients, a Single Center Experience.

Patients with COVID-19 are at risk of developing secondary complications such as invasive pulmonary aspergillosis and mucormycosis. This is a retrospective study including all cancer children diagnosed with COVID-19-associated pulmonary fungal infection (CAPFI) during the period 2020-2021. A total of 200 patients were diagnosed with COVID-19, out of which 21 (10%) patients were diagnosed with CAPFI, 19 patients (90%) with COVID-aspergillosis (CAPA), and 2 (10%) patients with COVID-mucormycosis (CAM). Patients with CAPFI were classified using the "2020 ECMM/ISHAM consensus criteria"; proven in 2 (10%) patients, probable in 12 (57%), and possible in 7 (33%) patients. Although the hematological malignancy patients were already on antifungal prophylaxis, breakthrough fungal infection was reported in 16/21 (75%), 14 (65%) patients had CAPA while on echinocandin prophylaxis, while 2 (10%) patients had CAM while on voriconazole prophylaxis. Overall mortality was reported in 8 patients (38%) while CAPFI-attributable mortality was reported in 4 patients (20%). In conclusion, clinicians caring for pediatric cancer patients with COVID-19 should consider invasive pulmonary fungal infection, even if they are on antifungal prophylaxis, especially with worsening of the clinical chest condition. A better understanding of risk factors for adverse outcomes may improve clinical management in these patients.

COVID-19, Mucormycosis and Cancer: The Triple Threat-Hypothesis or Reality?

COVID-19 has been responsible for widespread morbidity and mortality worldwide. Invasive mucormycosis has death rates scaling 80%. India, one of the countries hit worst by the pandemic, is also a hotbed with the highest death rates for mucormycosis. Cancer, a ubiquitously present menace, also contributes to higher case fatality rates. All three entities studied here are individual, massive healthcare threats. The danger of one disease predisposing to the other, the poor performance status of patients with all three diseases, the impact of therapeutics for one disease on the pathology and therapy of the others all warrant physicians having a better understanding of the interplay. This is imperative so as to effectively establish control over the individual patient and population health. It is important to understand the interactions to effectively manage all three entities together to reduce overall morbidity. In this review article, we search for an inter-relationship between the COVID-19 pandemic, emerging mucormycosis, and the global giant, cancer.

Preliminary Experience in Post-COVID-19 Mycoses: A Pathologist's Perspective.

Background Coronavirus disease is caused by the severe acute respiratory syndrome coronavirus-19. Because of co-morbidities and indiscriminate use of steroids and antibiotics, the incidence of opportunistic fungal infections has increased in COVID-affected individuals. Aims and objectives The aim of the study is to analyze the various tissue reaction patterns of COVID-19-associated mucormycosis in the surgical debridement specimens using routine hematoxylin and eosin (H&E) stain and special stains like periodic acid-Schiff (PAS), Grocott-Gomori's methenamine silver (GMS), Masson trichrome (MT) and Prussian blue (PB), and to understand the pathogenesis of COVID-19 sequelae. Materials and methods This retrospective observational study was conducted after the approval from the Institute Human Ethical Committee (IHEC) on 45 tissue samples of COVID-associated mucormycosis using routine H&E and histochemical stains such as PAS, GMS, MT, and PB. Detailed demographic profiles, clinical information, radiological findings, and relevant microbiological data in available cases, like reports on potassium hydroxide (KOH) mount preparation, and fungal culture reports on Saboraud's Dextrose Agar (SDA) medium were collected. The different histomorphological tissue reaction patterns were observed and analyzed. Results All the surgical debridement specimens from post-COVID cases had histomorphology of mucormycosis displaying broad, aseptate, ribbon-like fungal hyphae with right-angle branching (45/45). Six of the 45 cases also reveal thin, narrow septate, acute angle branching hyphae, indicating co-existing Aspergillosis (6/45). The histological tissue reaction patterns observed were categorized as extensive tissue necrosis (100%), vascular proliferation (82%), angioinvasion (58%), giant cell reaction (53%), fibrin thrombi (47%), septic thrombi and angiodestruction (40%), fungal osteomyelitis (33%), necrotizing granulomas (31%). Conclusion This study infers that post-COVID-19 associated mucormycosis, alterations in the local tissue microenvironment are found to have a favorable effect on colonizing fungi and result in destructive tissue reactions such as angioinvasion, angiodestruction, necrosis, necrotizing granulomas, suppurative inflammation, and iron pigment deposition. The spectrum of morphological changes reflects the host's immune status.

Twitter sentiment analysis for COVID-19 associated mucormycosis.

Purpose: COVID-19-associated mucormycosis (CAM) was a serious public health problem during the second wave of COVID-19 in India. We planned to analyze public perceptions by sentiment analysis of Twitter data regarding CAM. Methods: In this observational study, the application programming interface (API) provided by the Twitter platform was used for extracting real-time conversations by using keywords related to mucormycosis (colloquially known as "black fungus"), from May 3 to August 29, 2021. Lexicon-based sentiment analysis of the tweets was done using the Vader sentiment analysis tool. To identify the overall sentiment of a user on any given topic, an algorithm to label a user "k" based on their sentiments was used. Results: A total of 4,01,037 tweets were collected between May 3 and August 29, 2021, and the peak frequency of 1,60,000 tweets was observed from May 17 to May 23, 2021. Positive sentiment tweets constituted a larger share as compared to negative sentiment tweets, with weekly variations. A temporal analysis of the demand for utilities showed that the demand was high in the initial period but decreased with time, which was associated with the availability of resources. Conclusion: Sentiment analysis using Twitter data revealed that social media platforms are gaining popularity to express one's emotions during the ongoing COVID-19 pandemic. In our study, time-based assessment of tweets showed a reduction over time in the frequency of negative sentiment tweets. The polarization in the retweet network of users, based on sentiment polarity, showed that the users were well connected, highlighting the fact that such issues bond our society rather than segregating it.

Sublabial Approach Versus Modified Denker's Procedure: A Comparative Study of Pre-maxillary Tissue Clearance in Covid-Associated Mucormycosis.

To compare the efficacy of the sublabial and modified Denker's procedure in clearance of fungal disease from the anterior wall of maxilla and the pre-maxillary area i.e. the difficult areas of maxillary sinus. A prospective observational study was conducted over a period of 2 months (April 21-June 21) in the ENT department of Sawai Man Singh hospital, Jaipur. All the patients with clinical involvement of the premaxilla or the cheek abutting the anterior wall of maxilla were included in the study population. Cases matched in both groups were subjected to debridement either by the sublabial or the modified denker's approach. Outcomes were measured by assessing the daily CRP values, post-operative DNE every 3 days after pack removal, and imaging at the end of 1 month. Repeat biopsies were performed in patients that still had persistent symptoms after getting operated on. 16 of the 60 patients (26.6%) operated on by the endoscopic approach showed evidence of residual disease on follow-up whereas only 5 patients (9.6%) in the other category had a similar outcome. Most of the recidivism was seen in the anterior maxilla. Lower rates of complications were found following debridement by the sublabial approach. Since the sublabial approach is the most direct approach for the key areas of fungal involvement of maxillary sinus, it is recommended over the modified Denker's procedure for disease clearance from pre maxilla and the anterior wall of maxillary sinus. This view is also supported by the lower rates of complications encountered following the former.

Pathogenesis and Pathology of COVID-Associated Mucormycosis: What Is New and Why.

Purpose of Review: There is global increase in the incidence of mucormycosis. However, a sudden increase in the COVID-associated mucormycosis (CAM) was noted, particularly in India, during the second wave of the COVID-19 pandemic. The interplay of factors involved in the pathogenesis is complex. In this review, the influence of pre-existing disease, exaggerated risk factors, altered milieu due to COVID-19 itself and the consequences of its treatment on the host pathogen interactions leading to the disease and morphology of the fungus will be highlighted. Recent Findings: Hyperglycemia, acidosis, available free iron, lowered host defenses, and the fungal virulence factors promote the growth of Mucorales. There is a high background prevalence of diabetes mellitus (DM) in India. Uncontrolled or undiagnosed DM, COVID-19 itself, and inappropriate administration of corticosteroids in high doses and for prolonged periods result in hyperglycemia. Diabetic ketoacidosis (DKA) and metabolic acidosis due to hypoxia or renal failure contribute to acidic pH and dissociate bound iron from serum proteins. The host defenses are lowered due to COVID-19-induced immune dysregulation, hyperglycemia itself, and administration of corticosteroids and immune suppressants for the treatment of COVID-19. The altered metabolic milieu in the local microenvironment of nose and paranasal sinuses (PNS) promotes specific interaction of glucose-regulated protein-78 (GRP-78) on host cells with spore coat protein homologue (CotH 3) on Mucorales resulting in rhino-orbito-cerebral mucormycosis (ROCM) as the predominant clinical form in CAM. The pathology is extensive soft tissue involvement with angioinvasion and perineural invasion. Melanized hyphae and sporangia were seen on histopathology, which is unique to CAM. While many factors favor the growth of Mucorales in CAM, hyperglycemia, hyperferritinemia, and administration of hyperbaric oxygen result in reactive oxygen species (ROS) and inadequate humidification results in dehydration. Melanization is possibly the adaptive and protective mechanism of Mucorales to escape the unfavorable conditions due to the treatment of COVID-19. Summary: High background prevalence of DM, inappropriate administration of corticosteroids and immune dysregulation due to COVID-19 favor the growth of Mucorales in CAM. Melanization of Mucorales hyphae and sporangia on histopathology probably represent adaptive and protective mechanism due to the treatment with hyperbaric oxygen with inadequate humidification as well as the metabolic alterations.