Mucormycosis: An Epidemic Complicating the COVID-19 Pandemic.

COVID-19 is a relatively new disease whose complete pathogenesis and complications have not been elucidated. Apart from the morbidity and mortality caused by the virus itself, it is noted that patients affected with this virus have a higher susceptibility to bacterial and fungal co-infections. Mucormycosis is a rare and life-threatening fungal infection generally associated with uncontrolled diabetes mellitus and immunosuppression. It tends to rapid disease progression and poor prognosis if not diagnosed and managed promptly. There has been a sudden increase in the number of mucormycosis cases in patients with moderate to severe COVID-19 infection in the past few months. Herein, we present a series of 10 mucormycosis cases diagnosed over one week.

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. METHOD: 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.

Atypical presentations of fungal osteomyelitis during post COVID-19 outbreak - Case series.

Introduction: Mucormycosis and Aspergillosis are opportunistic fungal infections causing significant morbidity and mortality. Post the outbreak of COVID-19, these fungal osteomyelitis have seen a global rise with few atypical presentations noted. Case report: Current case series reports three such atypical presentations of fungal osteomyelitis including mandibular fungal osteomyelitis in two patients, fungal osteomyelitis mimicking space infection in a middle aged male, and suspected mixed fungal osteomyelitis involving maxillary sinus. Aggressive surgical debridement was indicated along with institution of antifungal therapy (Liposomal Amphotericin B, and Posaconazole). The fungal osteomyelitis was successfully treated with surgical and medical management with no recurrence. Discussion: The injudicious use of corticosteroids in COVID-19 patients along with their immunocompromised status increases their susceptibility to opportunistic fungal osteomyelitis. Prompt and aggressive surgical intervention along with antifungal therapy is important after diagnosing fungal osteomyelitis, as a delay could increase the mortality rate considerably.

BCG vaccination impact on mortality and recovery rates in COVID-19: A meta-analysis.

COVID-19 is a pandemic caused by SARS-CoV-2 virus which is a very worrisome public health emergency. In this study, we compared the mortality rate and recovery rate in countries with and without BCG vaccination policy. The data of mortality of COVID-19 was extracted from worldometer (https://www.worldometers.info/coronavirus/) on 26th July 2020. The data of countries where BCG vaccination is being done for all individuals is taken from BCG world atlas (http://www.bcgatlas.org/index.php), updated in 2017. BCG vaccination policy recommended countries are intervention group versus countries without BCG vaccination policies which are regarded as control group. Pooled analysis of countries with and without BCG vaccination policy revealed mortality rate of 1.31% (95%CI - 1.31% to 1.32%; I2 = 100%, p<0.01) and 3.25% (95%CI - 3.23% to 3.26%; I2 = 100%, p<0.01), respectively. The recovery rates in two country groups were found to be 72.60% (95%CI - 72.57% to 72.63%) and 55.94% (95%CI - 55.90% to 55.98%), respectively. 52 individuals need to be BCG vaccinated to prevent one death (NNT = 52). In BCG vaccination program countries, there is statistically and clinically significant less mortality (p<0.001) as compared to countries without BCG policy. Our findings corroborate the hypothesis that BCG vaccination may provide protection from COVID-19. High quality evidence from randomised controlled trials are required to establish causality between BCG vaccination and protection from severe COVID-19.

Does Bacille Calmette-Guérin Vaccination Provides Protection against COVID-19: A Systematic Review and Meta-analysis.

BACKGROUND: Lower morbidity and mortality in few geographic locations on the globe suffering with SARS-CoV-2 has been associated with the existing or previously followed long-standing Bacille Calmette-Guérin (BCG) vaccination policy among infants. However, does it hold true that today after years of BCG vaccination, few adults have better prognosis or is it just confounding due to differential disease burden, population density, testing facilities, or improper reporting. The purpose was to evaluate and correlate this effect systematically. METHODS: Detailed electronic search for randomized controlled trials (RCTs) and observational studies in PubMed, Cochrane Library, and ClinicalTrials.gov for eligible studies was performed. RESULTS: One hundred and fourteen studies were yielded on search strategy and 28 observational studies were finally included for analysis. From our results, we can say that BCG vaccination causes a decrease in COVID-19 incidence and mortality. However, these results must be interpreted cautiously as lot of confounding factors were present in included studies, which can affect the outcome. CONCLUSION: The evidence of BCG vaccination for the protection against COVID-19 cannot be ruled out as evidence from many studies support the hypothesis, but the evidence of well-conducted RCTs and observational studies can strengthen the evidence. REGISTRATION NUMBER: PROSPERO (International Prospective Register of Systematic Reviews) database (CRD42020204466).

Surgical & medical management of ROCM (Rhino-orbito-cerebral mucormycosis) epidemic in COVID-19 era and its outcomes - a tertiary care center experience.

OBJECTIVE: To evaluate the outcome of patients with ROCM (Rhino-orbito-cerebral mucormycosis) following their medical and surgical management. MATERIALS AND METHODS: It is a prognostic study based in a tertiary care center in North-Western India. Patients who developed ROCM post COVID-19 infection from 1st September 2020 to 30th June 2021 were included in this study. Surgical debridement and administration of antifungal therapy was done for the post-COVID-19 ROCM patients. Disease progression and survival was studied up to 5 months of follow-up in the second wave. RESULTS: A total of 145 ROCM patients were included. The mean age at presentation, male: female ratio was 48.2 years and 2:1 respectively. As per our proposed new staging system and treatment strategy, the majority of patients belonged to stage II (31.72%) and stage III (31.03%). On a follow-up period of 5 months, 26 (18%) patients have lost their life and rest of the patients are on strict follow-up. CONCLUSION: ROCM is an extremely aggressive fungal infection which rapidly became an epidemic following the COVID-19 pandemic. The diverse and unique presentation led us to evolve a new strategy to classify and manage these patients.

Magnetic Resonance Imaging in Coronavirus Disease - 2019 Associated Rhino-Orbital-Cerebral Mucormycosis (CA-ROCM) - Imaging Analysis of 50 Consecutive Patients.

BACKGROUND AND PURPOSE: Rhino-orbital-cerebral mucormycosis has emerged as a major opportunistic infection in patients with COVID-19. High clinical suspicion and prompt imaging are crucial for early diagnosis and management. Our study evaluates imaging characteristics of patients with COVID-19 associated Rhino-orbital-cerebral Mucormycosis (CA-ROCM) in a tertiary care hospital in India. MATERIALS AND METHODS: A retrospective analysis of clinical and imaging data of patients with CA-ROCM who presented between December 2020 to June 2021 was performed. All patients had microbiologically or histologically proven sino-nasal mucormycosis along with documented SARS-CoV-2 positive RT-PCR test and/or classical lung imaging features of COVID-19 infection. The extent of sinus involvement, bony erosions, extra-sinus soft tissue extension, orbital-intracranial invasion, perineural spread, and vascular complications were assessed. RESULTS: Fifty patients were included for the final analysis. Diabetes was the most common associated comorbidity. Seven patients presented with stage I disease, 18 patients with stage II, and 25 patients with stage III disease. The stage of disease showed a positive statistical correlation with HbA1c levels using Pearson's correlation. The common imaging features were "Black turbinate sign" and nonenhancing sino-nasal mucosa (82%), orbital involvement (76%), and diffusion restriction in the optic nerve (24%). Intracranial involvement was seen as perineural extension into the brain (42%), cerebritis (30%), and internal carotid artery involvement (16%). CONCLUSIONS: CA-ROCM is an acute invasive fungal sinusitis with an aggressive clinical course. Black-turbinate sign and peri-antral soft tissue infiltration are early features, whereas extra-nasal tissue infarction, optic nerve diffusion restriction, and vascular invasion are seen with advanced disease.

Systematic review and meta-analysis of efficacy and safety of hydroxychloroquine and chloroquine in the treatment of COVID-19.

Repurposed drugs like hydroxycloroquine (HCQ) and chloroquine (CQ) are being tested for potential therapeutic role in COVID-19. We aimed to evaluate efficacy and safety of HCQ and CQ in COVID-19. Using PubMed, EMBASE, medRxiv, Google Scholar, clinicaltrials.gov, electronic search was carried out to identify relevant articles till June 2020 with re-evaluation in last week of November 2020. Observational and interventional clinical studies comparing efficacy of CQ or HCQ to standard management or other drug/s for SARS-CoV-2 infection patients were included. Cochrane review manager version 5.3 was used for synthesis of meta-analysis results. For randomized controlled trials, risk of bias was assessed using Cochrane Collaboration risk of bias assessment tool, version 2.0 (ROB-2). ROBINS-I was used for quality assessment of observational studies. Overall evidence quality generated by review was graded as per GRADE Recommendation. A total of 903 studies were screened. Nineteen studies were included in synthesis of meta-analysis with total of 4,693, 1,626, and 6,491 patients in HCQ/CQ, HCQ/CQ + AZ and control groups, respectively. HCQ/CQ treatment was associated with significantly increased rates of virological cure (OR = 2.08, 95%CI = 1.36-3.17; P = 0.0007) and radiological cure (OR = 3.89, 95%CI = 1.35 - 11.23; P = 0.01) compared to control. HCQ/CQ had no difference in unadjusted mortality rate (unadjusted OR = 0.98 95% CI = 0.70-1.37, P = 0.89, random effect model) and adjusted hazard ratio for mortality (adjusted HR = 1.05, 95%CI = 0.86--1.29; P = 0.64). However, a significant increase in odds of disease progression (OR = 1.77, 95%CI = 1.46-2.13; P < 0.00001) and QT prolongation (OR = 11.15, 95%CI = 3.95-31.44; P < 0.00001) was noted. The results with HCQ/CQ and azithromycin combination were similar to HCQ/CQ mono-therapy. In the light of contemporary evidence on effectiveness of HCQ/CQ, judicious and monitored use of HCQ/CQ for treatment of COVID-19 patients is recommended in low to middle income countries with emphasis on no mortality benefit. Registration number of Systematic review. Register in PROSPERO database: cRD42020187710.

Rapid Response Preparedness for Management of Post-Covid Invasive Rhino-Orbito-Cerebral Fungal Infections: Experience from a Tertiary Care Government Institute in India.

Sudden surge of Post Covid-19 Rhino-orbito-mucormycosis cases has left entire ENT fraternity in the center of a war room. We present a quick administrative preparedness for this situation in a tertiary care Government Institute in India. This model may serve as a reference for other centers.

Efficacy and safety of remdesivir in COVID-19 caused by SARS-CoV-2: a systematic review and meta-analysis.

OBJECTIVES: Evaluation of remdesivir, an RNA polymerase inhibitor, for effectiveness in adults with COVID-19. DATA SOURCES: Electronic search for eligible articles of PubMed, Cochrane Central and clinicaltrials.gov was performed on 20 September 2020. PARTICIPANTS AND STUDY ELIGIBILITY CRITERIA: Only randomised controlled trials (RCTs) evaluating efficacy of remdesivir in COVID-19 were included for meta-analysis. INTERVENTIONS: Remdesivir was compared with standard of care. PRIMARY AND SECONDARY OUTCOMES: Primary outcome was mortality and secondary outcomes were time to clinical improvement and safety outcomes like serious adverse events, respiratory failure. STUDY APPRAISAL AND SYNTHESIS METHODS: Data synthesis was done with Cochrane review manager 5 (RevMan) V.5.3. Cochrane risk of bias V.2.0 tool was used for methodological quality assessment. The GRADE pro GDT was applied for overall quality of evidence. RESULTS: 52 RCTs were screened and 4 studies were included in analysis, with total of 7324 patients. No mortality benefit was observed with remdesivir versus control group (OR=0.92 (95% CI 0.79 to 1.07), p=0.30, moderate quality evidence). Significantly higher rates of clinical improvement (OR=1.52 (95% CI 1.24 to 1.87), p<0.0001, low quality) and faster time to clinical improvement (HR=1.28 (95% CI 1.12 to 1.46), p=0.0002, very low quality) was observed with remdesivir versus control group. Significant decrease was found in the risk of serious adverse events (RR=0.75 (95% CI 0.62 to 0.90), p=0.0003, low quality); however, no difference was found in the risk of respiratory failure (RR=0.85 (95% CI 0.41 to 1.77), p=0.67, very low quality evidence) with remdesivir. CONCLUSIONS: As per the evidence from current review, remdesivir has shown no mortality benefit (moderate quality evidence) in the treatment of COVID-19. From a cost-benefit perspective, it is our personal opinion that it should not be recommended for use, especially in low and lower middle income countries. TRIAL REGISTRATION NUMBER: PROSPERO registration number: CRD42020189517.

Transformational Effect of COVID Pandemic on Postgraduate Programme in Oral and Maxillofacial Surgery in India-A Trainee Perspective.

Background and purpose: The purpose of the survey was to evaluate transformation in mode of teaching during the COVID pandemic on a postgraduate program in oral and maxillofacial surgery in India. Methods: A standardised e-questionnaire was created on Google Forms™ and was shared using emails and WhatsApp™. A total of 103 postgraduate students of oral and maxillofacial surgery from different universities participated in this cross-sectional survey. The collected data were analysed using bivariate and multivariate analysis. Results: A total of 95.1% of postgraduates in the survey believed that their overall regular speciality work was deprived during first 5 months of COVID. 90.3% participants accepted that webinar/online teaching program become more beneficial for their academics. But 78.1 % participants think that because of overburdening of these academic sessions, they have reduced the enthusiasm in attending them. Conclusion: This survey highlighted the intense negative impacts of this pandemic on the postgraduate program from the eyes of the trainees themselves. This triggers us to hasten this process of medical education transformation in a way to cope with any such calamity with minimal consequences.

Oral and Maxillofacial Minor Surgery Practice Post-COVID 2019 Pandemic - An Insight.

COVID-19, a worldwide pandemic, has given an awakening and introspective moment for all surgeons involved with aerosol-generating procedures. We ought to modify our practices to learn to live with it if we wish to prevail over it. This article outlines similar small changes that can be done in our minor maxillofacial surgery practice to safeguard both patients and healthcare workers.