An overview of opportunistic fungal infections associated with COVID-19.

The COVID-19 survivors and long-term steroid administered patients exhibit a variety of fungal co-infections. The lives of COVID-19 patients and survivors are hampered by fungal species of the genera Candida, Aspergillus, and Mucor. There have been cases of mucormycosis, aspergillosis, and candidiasis in COVID-19 patients. The treatments given to these opportunistic fungal infections include polyene like amphotericin B, azoles including imidazoles like ketoconazole, miconazole, and triazoles like fluconazole, voriconazole, itraconazole, Echinocandin derivatives like- caspofungin, micafungin, immunomodulatory therapy, granulocyte transfusion, etc. A successful recovery and the reduction of fatalities depend on prompt diagnosis and treatment. To reduce mortality, advanced techniques to identify such uncommon infections at a very early stage are necessary. This review's goal is to provide a summary of the systemic and superficial opportunistic fungal infections that the COVID-19 survivors were dealing with, including information on illness incidence, pathogenicity, and treatment.

Post Covid-19 Sinonasal Candidiasis: A Crisis Within the Pandemic.

The aim of this study was to find out the association of sinonasal candidiasis and Covid-19 infection. A prospective observational study was conducted at a tertiary care centre from April to September 2021, involving all patients with invasive candidiasis of the paranasal sinuses having a history of Covid-19 infection. A total of 18 patients of covid associated sinonasal candidiasis among the 475 cases of fungal rhinosinusitis were studied. All patients had involvement of nose and sinuses and 2 patients had orbital involvement with no loss of vision, while 3 had intracranial extensions and 1 had pulmonary involvement. Mandible was involved in 1 patient alone, while the maxilla and palate were involved in 5 patients. 15 patients were hypertensive, 12 diabetics and 1 had aplastic anaemia. Cultures showed that 8 patients had C. parapsilosis, 5 had C. albicans, 3 had C. tropicalis and 2 had mixed fungal infections. All patients underwent surgical debridement and antifungal administration. They were followed up for a minimum of 3 months. There was only one mortality (with aplastic anaemia), rest 17 were disease free at the time of writing this article. This is perhaps the first case series of post covid sinonasal candidiasis in the world. Invasive sinonasal candidiasis is a newer sequela of COVID-19 infection. Uncontrolled diabetes and over-zealous use of steroids at the time of Covid-19 are few of the known risk factors. Early surgical intervention and anti-fungal treatment should be sought for management.

Factors Associated with Outcome in Patients Managed for Invasive Fungal Infections at the Infectious Diseases Department of a Tertiary Care Hospital

Objective: To look for the factors associated with outcomes in patients managed for invasive fungal infections at the Infectious Diseases Department of a Tertiary Care Hospital Study Design: Comparative cross-sectional study Place and Duration of Study: Department of Infectious Diseases, Pak Emirates Military Hospital, Rawalpindi Pakistan,from Apr 2021 to Sep 2022. Methodology: A total of 90 patients with a different types of invasive fungal infections diagnosed by consultant infectious diseases were recruited. First, they were given standard treatment for fungal infection;they were diagnosed as per guidelines. Then, they were followed up for one month to look for an outcome. Results: Out of 90 patients with invasive fungal infections included in the study, 62(68.8%) had a good outcome, while 28(31.2%) had a poor outcome. The mean age of the patients recruited in our study was 39.54±6.27 years. Of all the participants, 65(72.2%) patients were male, while 25(27.8%) were female. Statistical analysis revealed that poorly controlled diabetes, COVID-19 infection and HIV positive were statistically significantly associated with poor outcomes in our study participants (p-value<0.05). Conclusion: The Considerable number of patients with invasive fungal infections had a poor outcome in our study. The presence of poorly controlled diabetes, COVID-19 infection and being HIV positive were the factors associated with poor outcomes in our study participants.

Effect of the Changing Climate and Urban Ecology on Spreading of Infectious Diseases Including SARS-CoV-2

Globalisation, industrialisation, and ease of international travel are making a huge impact on urban ecology. It is also influencing the climate, exaggerated by increased pollution, global temperature, and greenhouse gasses. All these factors together play a pivotal role in the increased emergence of infectious human diseases like fungal, bacterial, and viral. Many microorganisms are commensal and coâ€exist as microflora of healthy individuals. However, when the immune system is compromised due to disruption of mucosal barriers or presence of other environmental factors including increased air pollution, these microorganisms get an opportunity to invade and cause infections. In a similar way, the ongoing COVIDâ€19 pandemic, mediated by SARSâ€CoVâ€2, has also led to an increase in a number of nosocomial infections and secondary infections or superinfections like bacterial, fungal, and viral. Several studies have suggested that adaptation to higher temperatures is one of the key contributors to the emergence of many fungus like Candida auris and mucormycetes. Even bacteria like Acinetobacter baumannii, Mycobacterium tuberculosis, etc. or viral infections mediated by Ebola, H1N1, Encephalitis, and SARSâ€CoVâ€2 become more virulent with change in climate and urban ecology. Lifestyle change including uncontrolled intake of animal foods which possibly resulted in the zoonotic transfer of SARSâ€CoVâ€2 to humans, an increase in sexually transmitted diseases including AIDS due to uncontrolled lifestyles in a modern urban society are few other examples. Although these are the results of humans’ need and greed, it is not too late to take actions towards sustainable developments and adopting preventive plans to save the future world. This chapter mainly attempts to understand how such changes in environmental factors, altered climate, and urban ecology can lead to emergence of several infectious diseases, followed by a discussion of preventive measures to keep a steady but sustainable global development of human lives. © 2022 John Wiley & Sons Ltd.

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Mucormycosis an Emerging Fungal Infection Associated with COVID-19- A Case Report

Introduction: Mucormycosis is an exceptional but rising fungal infection correlated with the COVID-19 disease. COVID-19 positive patients exhibiting severe symptoms admitted in the ICU have an increased susceptibility to develop bacterial and fungal infection. We hereby report a case of oral mucormycosis that is seen in a patient in post COVID-19 infection. Case Presentation: A 65-year-old woman presented to our institution, with the chief complaint of ulceration in her right palate region for the past 7 days along with pyrexia and generalised malaise. The patient reported to have recovered from COVID-19 infection recently. She presented with medical history of diabetes and hypertension for past 8 years. Post recovery from COVID-19 infection the patient developed an ulcer in the hard palate. Treatment: Surgery was done under General anesthesia. Maxillectomy was done with aggressive debridement of necrotic tissue. Bilaterally periosteal flap was approximated and suture was placed. Conclusion: The extensive use of steroids and broad-spectrum antibiotics in COVID-19 treatment may raise the risk of fungal infections. Medical practitioners should be aware of the possibility of invasive secondary fungal infections in patients with COVID-19 infection.

Transcriptome in Human Mycoses

Mycoses are infectious diseases caused by fungi, which incidence has increased in recent decades due to the increasing number of immunocompromised patients and improved diagnostic tests. As eukaryotes, fungi share many similarities with human cells, making it difficult to design drugs without side effects. Commercially available drugs act on a limited number of targets and have been reported fungal resistance to commonly used antifungal drugs. Therefore, elucidating the pathogenesis of fungal infections, the fungal strategies to overcome the hostile environment of the host, and the action of antifungal drugs is essential for developing new therapeutic approaches and diagnostic tests. Large-scale transcriptional analyses using microarrays and RNA sequencing (RNA-seq), combined with improvements in molecular biology techniques, have improved the study of fungal pathogenicity. Such techniques have provided insights into the infective process by identifying molecular strategies used by the host and pathogen during the course of human mycoses. This chapter will explore the latest discoveries regarding the transcriptome of major human fungal pathogens. Further we will highlight genes essential for host–pathogen interactions, immune response, invasion, infection, antifungal drug response, and resistance. Finally, we will discuss their importance to the discovery of new molecular targets for antifungal drugs. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2014, 2022.

Antifungal Drug Resistance: An Emergent Health Threat.

Fungal infections, named mycosis, can cause severe invasive and systemic diseases that can even lead to death. In recent years, epidemiological data have recorded an increase in cases of severe fungal infections, caused mainly by a growing number of immunocompromised patients and the emergence of fungal pathogenic forms that are increasingly resistant to antimycotic drug treatments. Consequently, an increase in the incidence of mortality due to fungal infections has also been observed. Among the most drug-resistant fungal forms are those belonging to the Candida and Aspergillus spp. Some pathogens are widespread globally, while others are endemic in some areas only. In addition, some others may represent a health threat for some specific subpopulations and not for the general public. In contrast to the extensive therapeutic armamentarium available for the antimicrobial chemotherapeutic treatment of bacteria, for fungal infections there are only a few classes of antimycotic drugs on the market, such as polyenes, azoles, echinocandins, and a few molecules are under trial. In this review, we focused on the systemic mycosis, highlighted the antifungal drug compounds available in the pipeline, and analyzed the main molecular mechanisms for the development of antifungal resistance to give a comprehensive overview and increase awareness on this growing health threat.

Evaluation of risk factors, clinico-radiographic presentations of COVID-associated mucormycosis in the maxillofacial region reporting to a tertiary care dental facility.

Purpose: To evaluate the prevalence of risk factors associated with COVID-associated mucormycosis (CAM) in the maxillofacial region with emphasis on clinical and radiological characteristics of the disease reporting to the dentists. Methods: Archival records of the patients diagnosed with rhino-cerebral mucormycosis through histopathology or culture, were screened and 266 records were included. These records were divided into three groups-previously diabetic (PD, n = 122), recently diagnosed diabetic (RD, n = 105) and non-diabetic (ND, n = 39). All the records were evaluated and compared among the three groups for the duration of presentation, history of co-existing medical conditions, the association of treatment given during COVID-19, and the clinical and radiographic presentations of the disease. Results: The results confirmed uncontrolled diabetes mellitus as the major risk factor for the disease. The prevalence of steroid administration was lower in our study in contrast to previous literature. The risk factors and treatment rendered during COVID-19 did not differ significantly among the three groups (p > 0.05). The findings indicate that the disease was milder and progressed more slowly in the ND group, both clinically and radiographically, and it had close resemblance to odontogenic infection. Conclusion: Patients with early CAM mimicked the odontogenic infection and were more likely to report in a dental setup. Hence, a multidisciplinary and holistic management approach is necessary.

Rhino-orbital mucormycosis in a Mexican patient with COVID-19: Case report.

BACKGROUND: A variety of bacterial and fungal co-infections may be attributed to the coronavirus disease 2019 (COVID-19), particularly in people who already have a medical condition such diabetes mellitus or those who received large dosages of steroids. CASE REPORT: We described a 52-year-old diabetic man who was receiving high doses of dexamethasone and antibiotics while receiving ambulatory care for COVID-19 pneumonia. His anterior rhinoscopy revealed a necrotic scab, and a sample confirmed Mucor spp. He underwent surgery and was given amphotericin as a result of the severity of the condition, palpebral ptosis, and right ocular palsy he was experiencing. The patien ́s progression was satisfactory. CONCLUSIONS: pre-existing diabetes mellitus, previous steroid and antimicrobial use, as well as SARS-CoV-2 infection are some of the risk factors associated with Mucor spp. infection. Prompt detection of mucormycosis is important in the management of these affected patients.

ANTECEDENTES: A la enfermedad por coronavirus (COVID-19) se le han atribuido diversas coinfecciones bacterianas y fúngicas, especialmente en sujetos con enfermedades preexistentes (diabetes mellitus) o en quienes han recibido altas dosis de corticosteroides. REPORTE DE CASO: Paciente masculino de 52 años, con antecedente de diabetes mellitus, quien recibió altas dosis de dexametasona y antibióticos mientras recibía atención ambulatoria por neumonía secundaria a COVID-19. La rinoscopia anterior reveló una costra necrótica, y una muestra de exudado confirmó la coexistencia de Mucor spp. Debido a la complicación del cuadro clínico, ptosis palpebral y parálisis ocular derecha, se le administró anfotericina B y fue intervenido quirúrgicamente. La evolución del paciente fue satisfactoria. CONCLUSIONES: La diabetes mellitus preexistente, el consumo de corticosteroides y antimicrobianos, además de la infección por SARS-CoV-2 son factores de riesgo asociados con la infección por Mucor spp. Es importante la detección oportuna de mucormicosis en el tratamiento de estos pacientes.

Aspergillus hip arthritis in COVID-19 era: Two case reports

Corticosteroids have been a mainstay in the treatment protocols and guidelines of COVID-19. However, its use in high dosage or for extended duration renders patients immunocompromised after COVID-19 recovery, and thus, susceptible to secondary opportunistic infections. We report the two cases of septic hip arthritis due to Aspergillus species in corticosteroid immunosuppressed post-COVID-19 patients. One patient recovered successfully from the arthritis and subsequently underwent total hip arthroplasty with good outcome. The second patient presented late to us in a critical condition and had two comorbid conditions along with, due to which, in spite of all measures, could not be revived and succumbed to death. We highlight the issue of the rare cause of fungal hip arthritis in immunosuppressed post-COVID-19 patients and stress the necessity to remain vigilant and identify the causative organisms correctly, especially fungal pathogens in such susceptible populations in the present COVID-19 era.

Concomitant Presence of Mandibular Mucormycosis in a COVID Positive Patient: Report of A Rare Case

Reports of COVID-19 associated mucormycosis has exponentially increased in recent times, especially in patients with uncontrolled diabetes. It is reported to be associated with high mortality and morbidity rates and hence has emerged as a public health crisis. Covid-19 associated mucormycosis poses a diagnostic challenge for the Dentists as the clinical and radiological featuresare largely non-specific. The most common variant of mucormycosis in general is rhino-orbital and involvement of mandible is a rather uncommon presentation. Here we document a rare case of mucormycosis affecting the mandible with the concomitant presence of COVID19 infection in a diabetic patient.

Fungal Diseases and COVID-19

The physiological factors of COVID-19 infection and the environmental factors of treatment have predisposed a larger patient population to fungal infections. In this review, we provide an overview of the three most frequently documented fungal infections associated with COVID-19: aspergillosis, mucormycosis, and candidemia. For all three secondary infections, we review the literature making efforts to determine the incidence of infection, physiological or environmental causes of co-infection with COVID-19, and the mortality of infection both with and without COVID-19. These infections vary in their etiology in association with COVID-19 infection, in addition to their recommended treatments and mortality. Ultimately, we demonstrate the importance of early diagnosis of secondary infections and the proper identification of fungal pathogens for treatment purposes, while also highlighting research gaps in this new field. © 2023 Nova Science Publishers, Inc.

Secondary bacterial and fungal infections in critically ill COVID‐19 patients: Impact on antimicrobial resistance

Background: The primary burden among severely ill COVID-19 cases allocated to ICUs is secondary bacterial and fungal infections. Antimicrobial resistance is aggravated more likely by empiric overusing of antimicrobials. This study aimed to assess the microbiological profile of fungal and bacterial superinfections in laboratory confirmed COVID-19 cases and their antimicrobial susceptibility pattern. Methods: Various clinical samples were obtained from 117 critically ill COVID-19 patients in the clinical suspicion of secondary infections for assessing the pathogens accountable for the superinfections and their antimicrobial susceptibility pattern according to standard microbiological procedures. Results: Among 117 COVID‐19 patients allocated to ICU, 68 (58%) had secondary infections. The most prevalent infection was of the lower respiratory tract. Most infections were bacterial 85.8%. Gram-negative isolates were the most predominant strains, accounting for 71.7%. among them, Klebsiella pneumoniae 43.4 % and Acinetobacter baumannii 20.7% were the most predominant. Majority of the bacterial strains were multidrug-resistant, all gram-negative strains showed one hundred percent resistance rate to cephalosporins, amoxicillin, and amoxicillin-clavulanic. The lowest resistance was observed for tigecycline. All gram-positive strains were susceptible to linezolid and vancomycin. Additionally, all candida isolates were susceptible to the tested antifungals. Conclusions: In hospitalized severely ill COVID-19 patients, secondary infections are most frequently caused by Gram-negative pathogens exhibiting high rate of antibiotic resistance and are associated with poor outcomes. Strict adherence to infection control measures as well as regular microbiological surveillance are required. © 2020 The author (s).

Coronavirus Disease-2019 (COVID-19)-Positive Patients as Susceptible Hosts to Severe Fungal Coinfections

Since the World Health Organization (WHO) declared the pandemic of coronavirus disease-2019 (COVID-19) on March 11th, 2020, the world has faced a health crisis that includes challenges such as its diagnosis, treatment and prevention, resulting in more than 595 million confirmed cases worldwide and more than 6.4 million deaths (August 25th, 2022). The infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to the suppression of the immune system, particularly due to the storm of inflammatory cytokines (e.g., TNF-α, IFN-γ, IL-6, IL-2 and IL-1) and the reduction of anti-inflammatory cells (e.g., CD4+ and CD8+ T lymphocytes). These factors, when associated with the use of steroids, prolonged stay in the intensive care unit (ICU), older age, diabetes, cardiovascular and pulmonary diseases as well as inherited and acquired immunodeficiency, contribute to the colonization of other infectious agents, such as respiratory viruses, gram-positive and gram-negative bacteria, yeasts and filamentous fungi. The incidence of opportunistic fungal infections has increased significantly in patients with COVID-19, especially in individuals with critical medical conditions and presenting comorbidities, such as the ones cited above. The main fungal agents causing coinfections in these particular patients are Aspergillus spp., Candida spp. and fungi belonging to the order Mucorales. The similarity of clinical symptoms between COVID-19 and fungal infections, such as fever, dry cough, dyspnea, myalgia and headache, makes it harder to get a conclusive laboratory identification and diagnosis, which represents a challenge for treatment. To worsen this bad scenario, the available antifungals are substantially limited and some fungal species are intrinsically resistant to classical chemotherapeutic drugs used in the clinical settings. In parallel, the antifungals can also present drug interactions besides serious and severe side effects, such as hepatotoxicity and nephrotoxicity, which can greatly aggravate the patients' clinical condition. All these facts highlight the urgent need for early diagnosis of the fungal pathogens for the proper choice of antifungal treatment in order to combat these relevant yet still neglected diseases on a global scale. The present chapter focused on summarizing the main fungal infections reported in COVID-19-positive patients. © 2023 Nova Science Publishers, Inc.

A hospital-based study on COVID-19 patients with rhino-orbital mucormycosis

According to a published literature from the end of 2019 to the start of April 2021, India contributed approximately 71% of the global cases of mucormycosis in patients with COVID-19. In addition to this, hyperglycemia in diabetics, steroid therapy, and consequent metabolic acidosis and diabetic keto acidosis along with other risk factors such as prolonged hospitalization with or without mechanical ventilators increase the chance of infection. Aims and Objectives In our study, we suggested the risk factors, clinical features, appropriate investigations, and effective treatment to control the infection of post-COVID-19 rhino-orbital mucormycosis. After taking history of the patients (age, residential area, date of admission, symptoms of illness, comorbidities, ex-diabetes, hypertension or other major illness, treatment history during COVID infection or other regular medications of the patient, and ex-history of steroid intake), we noted the related clinical features of rhino-orbital mucormycosis of the patients.

Rhino-orbital mucormycosis in COVID-19 patients—a new threat?

BackgroundCoronavirus disease 2019 (COVID-19) is known to be associated with a myriad of viral, fungal, and bacterial co-infections. Rhino-orbital mucormycosis is a rare angio-invasive fungal infection which has shown a rising trend in the setting of COVID-19.Case presentationWe describe the imaging findings in 3 cases of rhino-orbital mucormycosis in patients with history of COVID-19. All cases had varying involvement of paranasal sinuses extending into the orbital compartment while case 3 had intracranial extension of infection.ConclusionsRhino-orbital mucormycosis can have aggressive necrosis of the involved paranasal sinuses and orbits with or without cerebral extension. Hence, the correct diagnosis is imperative as prompt antifungal drugs and surgical debridement can significantly reduce mortality and morbidity.

Cryptococcus neoformans, a global threat to human health.

BACKGROUND: Emerging fungal pathogens pose important threats to global public health. The World Health Organization has responded to the rising threat of traditionally neglected fungal infections by developing a Fungal Priority Pathogens List (FPPL). Taking the highest-ranked fungal pathogen in the FPPL, Cryptococcus neoformans, as a paradigm, we review progress made over the past two decades on its global burden, its clinical manifestation and management of cryptococcal infection, and its antifungal resistance. The purpose of this review is to drive research efforts to improve future diagnoses, therapies, and interventions associated with fungal infections. METHODS: We first reviewed trends in the global burden of HIV-associated cryptococcal infection, mainly based on a series of systematic studies. We next conducted scoping reviews in accordance with the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews using PubMed and ScienceDirect with the keyword Cryptococcus neoformans to identify case reports of cryptococcal infections published since 2000. We then reviewed recent updates on the diagnosis and antifungal treatment of cryptococcal infections. Finally, we summarized knowledge regarding the resistance and tolerance of C. neoformans to approved antifungal drugs. RESULTS: There has been a general reduction in the estimated global burden of HIV-associated cryptococcal meningitis since 2009, probably due to improvements in highly active antiretroviral therapies. However, cryptococcal meningitis still accounts for 19% of AIDS-related deaths annually. The incidences of CM in Europe and North America and the Latin America region have increased by approximately two-fold since 2009, while other regions showed either reduced or stable numbers of cases. Unfortunately, diagnostic and treatment options for cryptococcal infections are limited, and emerging antifungal resistance exacerbates the public health burden. CONCLUSION: The rising threat of C. neoformans is compounded by accumulating evidence for its ability to infect immunocompetent individuals and the emergence of antifungal-resistant variants. Emphasis should be placed on further understanding the mechanisms of pathogenicity and of antifungal resistance and tolerance. The development of novel management strategies through the identification of new drug targets and the discovery and optimization of new and existing diagnostics and therapeutics are key to reducing the health burden.