Hospital-treated serious and invasive aspergillosis and candidiasis infections during the COVID-19 pandemic: a retrospective analysis of Hospital Episode Statistics data from England.

OBJECTIVES: To investigate the impact of COVID-19 on the burden of hospital-treated Aspergillus and Candida infections in England. DESIGN: A retrospective study using Hospital Episodes Statistics data to estimate the burden of serious and invasive fungal infections (SIFIs) in all patients admitted in England during March 2018-February 2020 (pre-COVID-19) and during March 2020-October 2021 (the COVID-19 period). SETTING: Hospitals in England. POPULATION: All patients with codes corresponding to serious and invasive aspergillosis and candidiasis in any diagnosis position during their admission pre-COVID-19 and during the COVID-19 period. OUTCOME MEASURES: Age, spells, patient counts, mean length of stay, admission to critical care unit (CCU), length of stay in CCU, 30-day readmissions, failed discharges (readmission within 7 days) and comorbidities. RESULTS: During the COVID-19 period, hospitalisation spells with an invasive candidiasis code fell by 3.2% and spells with an aspergillosis code by 24.8%. Mean length of stay was higher for patients with aspergillosis with or without COVID-19 and candidiasis with or without COVID-19 during the pandemic than before the pandemic. During the pandemic, mean length of stay was higher for patients with aspergillosis with COVID-19 than those with aspergillosis alone but slightly lower for patients with candidiasis with COVID-19 than for those with candidiasis alone. Of patients with a diagnosis of COVID-19, 52.5% with aspergillosis and 60.0% with candidiasis were treated in CCU compared with 13.2% and 37.1%, respectively, without a COVID-19 diagnosis. The percentage of 30-day readmissions and failed discharges for patients with SIFI was higher for those with COVID-19 than for those without. CONCLUSIONS: The burden of aspergillosis and candidiasis has been affected by COVID-19. Aspergillosis diagnoses fell among hospitalised patients during the pandemic, while candidiasis continued to fluctuate in patterns similar to pre-COVID-19. A higher burden for patients with SIFI was observed, whether or not they also had a diagnosis of COVID-19. Our findings highlight extra considerations and burden on management of serious SIFI as a result of the COVID-19 pandemic.

Assessment of Risk Factors and Clinical Outcomes in Hospitalized COVID-19 Patients with Candida spp. Co-infections: Species Distribution and Antifungal Susceptibility Patterns of Isolates.

INTRODUCTION: Fungal co-infections are considered an important complication in hospitalized patients with SARS-CoV-2 that can be attributed to disease aggravation, increased mortality, and poor outcomes. This study was conducted to determine the species distribution and antifungal susceptibility patterns of Candida isolates from hospitalized COVID-19 patients in Shiraz, Iran, in addition to associated risk factors and outcomes of co-infections with Candida species. MATERIALS AND METHODS: In this single-center study, a total of 106 hospitalized COVID-19 patients were evaluated for clinical characteristics and outcomes. Species identification was performed by ITS1-5.8S-ITS2 gene sequencing. Antifungal susceptibility testing to fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, amphotericin B, and nystatin was determined according to the M27-A3/S4 CLSI protocol. RESULTS: Candida species were recovered from 48% (51/106) of hospitalized COVID-19 patients. Statistical analysis showed that patients who had heart failure, bacterial co-infection, and were receiving empirical antifungal therapy had a higher risk of developing Candida co-infection. In total, 71 Candida isolates were recovered, of which C. albicans (69%) was the most prevalent isolate. The majority of the Candida isolates were susceptible to all classes of tested antifungal drugs. DISCUSSION: Our results elucidate a high rate of Candida co-infections among hospitalized COVID-19 patients. Comorbidities such as heart failure, HTN, COPD, bacterial infections as well as therapeutic interventions including catheterization, mechanical ventilation, and ICU admission increased the risk of Candida spp. isolation from the bloodstream, respiratory tract and urine samples, which led to a higher in-hospital mortality rate. Additionally, obtained data clarified that empirical antifungal therapy was not as successful as anticipated.

Ramification of COVID-19 pandemic : Occurrence and impact of fungal infections in a tertiary care hospital (preprint)

Coronavirus disease 2019 (COVID-19) pandemic has been prevailing for more than a year associated with increased number of opportunistic invasive fungal infections in patients who have been critically ill or immunocompromised. In this retrospective study, details of various clinical specimens received from suspected patients of fungal infections were processed according to standard protocol were studied. The fungal infections were present in 64% (51/79) COVID-19 positive patients and 43% (163/381) COVID-19 negative patients) during the year 2021 during the second wave of COVID-19. Among COVID-19 infected patients, the fungal infection mostly observed was Candidiasis (63%) followed by Aspergillosis (15% ) and Mucormycosis (6%). The maximum samples positive in COVID-19 patients were urine samples followed by Serum (for Aspergillus Galactomannan). Among the urine and respiratory samples (BAL, Tracheal aspirate, Sputum) in COVID-19 positive patients, maximum positivity of Candida species was seen. Mucormycosis in COVID-19 positive patients was isolated in Nasal samples followed by tissue sample with Rhizopus arrhizus and Rhizopus homothallicus. There has been an increase in fungal co-infections during the COVID-19 pandemic which is a matter of great concern. Early diagnosis is essential for effective management of these patients.

Candida auris Discovery through Community Wastewater Surveillance during Healthcare Outbreak, Nevada, USA, 2022.

Candida auris transmission is steadily increasing across the United States. We report culture-based detection of C. auris in wastewater and the epidemiologic link between isolated strains and southern Nevada, USA, hospitals within the sampled sewershed. Our results illustrate the potential of wastewater surveillance for containing C. auris.

Evaluation of oral mucositis, candidiasis, and quality of life in patients with head and neck cancer treated with a hypofractionated or conventional radiotherapy protocol: a longitudinal, prospective, observational study.

BACKGROUND: Due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, recently, Radiotherapy (RT) protocols requiring fewer sessions (hypofractionated) have been used to shorten RT treatment and minimize patient exposure to medical centers, and decrease the risk of SARS-CoV-2 infection. METHODS: This longitudinal, prospective, observational study aimed to compare the quality of life (QoL) and the incidence of oral mucositis and candidiasis in 66 patients with head and neck cancer (HNC) who undergo a hypofractionated RT protocol (GHipo), total of 55 Gy for 4 weeks, or a conventional RT protocol (GConv), total of 66 - 70 Gy for 6 - 7 weeks. PURPOSE: To assess the incidence and severity of oral mucositis, the incidence of candidiasis, and QoL were evaluated using the World Health Organization scale, clinical evaluation, and the QLC-30 and H&N-35 questionnaires, respectively, at the beginning and the end of RT. RESULTS: The incidence of candidiasis did not show differences between the two groups. However, at the end of RT, mucositis had a higher incidence (p < 0.01) and severity (p < 0.05) in GHipo. QoL was not markedly different between the two groups. Although mucositis worsened in patients treated with hypofractionated RT, QoL did not worsen for patients on this regimen. CONCLUSIONS: Our results open perspectives for the potential use of RT protocols for HNC with fewer sessions in conditions that require faster, cheaper, and more practical treatments.

Opportunistic Candida Infections in Critical COVID-19 Patients.

The frequency of opportunistic fungal infections in critically ill patients whose intensive care unit stays are prolonged due to coronavirus disease 2019 (COVID-19) is higher than in the period before COVID-19. We planned this study to improve the management of Candida infections by defining the Candida species, the etiology of infections caused by Candida species, and the antifungal susceptibility of the species. This retrospective study included patients older than 18 hospitalized in the intensive care unit (ICU) with a definitive diagnosis of COVID-19 for seven months (from March 2021 to September 2021). All study data that we recorded in a standard study form were analyzed with TURCOSA (Turcosa Analytics Ltd. Co., Turkey, www.turcosa.com.tr) statistical software. The patients were evaluated in four groups as group 1 (candidemia patients, n = 78), group 2 (candiduria patients, n = 189), group 3 (control patients, n = 57), and group 4 (patients with candidemia in urine cultures taken before Candida was detected in blood culture, n = 42). Candida species were identified using both conventional and VITEK® 2 (BioMérieux, France) methods. The antifungal susceptibility of fungi was determined using the E test method. Of the 5,583 COVID-19 patients followed during the study period, 78 developed candidemia, and 189 developed candiduria. The incidence of candidemia (per 1,000 admissions) was determined to be 1.6. As a result of statistical analysis, we found that Candida albicans was the dominant strain in candidemia and candiduria, and there was no antifungal resistance except for naturally resistant strains. Candida strains grown in blood and urine were the same in 40 of 42 patients. Mortality was 69.2% for group 1, 60.4% for group 2, and 57.8% for group 3. Antifungals were used in 34 (43.5%) patients from group 1, and 95 (50.2%) from group 2. In the candidemia group without antifungal use, mortality was quite high (77.2%). Antifungal use reduced mortality in the group 2 (p < 0.05). Length of ICU stays, comorbidity, broad-spectrum antibiotics, and corticosteroids are independent risk factors for candidemia in critically ill COVID-19 patients. Our study contributes to the knowledge of risk factors for developing COVID-19-related candida infections. The effect of candiduria on the development of candidemia in critically ill COVID-19 patients should be supported by new studies.

On the Rise, Candida auris Outwits Treatments and Travels Incognito in Health Care Settings.

This Medical News feature examines the relatively newly identified fungus Candida auris, a hardy species that can resist treatment with antifungal agents, is highly contagious, and is associated with serious infections and significant mortality.

Defective antifungal immunity in patients with COVID-19.

The COVID-19 pandemic has placed a huge strain on global healthcare and been a significant cause of increased morbidity and mortality, particularly in at-risk populations. This disease attacks the respiratory systems and causes significant immune dysregulation in affected patients creating a perfect opportunity for the development of invasive fungal disease (IFD). COVID-19 infection can instill a significant, poorly regulated pro-inflammatory response. Clinically induced immunosuppression or pro-inflammatory damage to mucosa facilitate the development of IFD and Aspergillus, Mucorales, and Candida infections have been regularly reported throughout the COVID-19 pandemic. Corticosteroids and immune modulators are used in the treatment of COVID-19. Corticosteroid use is also a risk factor for IFD, but not the only reason for IFD in COVID -19 patients. Specific dysregulation of the immune system through functional exhaustion of Natural killer (NK) cells and T cells has been observed in COVID-19 through the expression of the exhaustion markers NK-G2A and PD-1. Reduced fungicidal activity of neutrophils from COVID-19 patients indicates that immune dysfunction/imbalance are important risk factors for IFD. The COVID-19 pandemic has significantly increased the at-risk population for IFD. Even if the incidence of IFD is relatively low, the size of this new at-risk population will result in a substantial increase in the overall, annual number of IFD cases. It is important to understand how and why certain patients with COVID-19 developed increased susceptibility to IFD, as this will improve our understanding of risk of IFD in the face of future pandemics but also in a clinical era of increased clinical immuno-suppression/modulation.

Surveillance diagnostic algorithm using real-time PCR assay and strain typing method development to assist with the control of C. auris amid COVID-19 pandemic.

Candida auris continues to be a global threat for infection and transmission in hospitals and long-term care facilities. The emergence of SARS-CoV-2 has rerouted attention and resources away from this silent pandemic to the frontlines of the ongoing COVID-19 disease. Cases of C. auris continue to rise, and clinical laboratories need a contingency plan to prevent a possible outbreak amid the COVID-19 pandemic. Here, we introduce a two-tier Candida auris surveillance program that includes, first, a rapid qualitative rt-PCR for the identification of high-risk patients and, second, a method to analyze the isolated C. auris for strain typing using the Fourier-Transform Infrared spectroscopy. We have performed this two-tier surveillance for over 700 at-risk patients being admitted into our hospital and have identified 28 positive specimens (4%) over a 1-year period. Strain typing analysis by the IR spectrum acquisition typing method, supplemented by whole genome sequencing, has shown grouping of two significant clusters. The majority of our isolates belong to circulating African lineage associated with C. auris Clade III and an isolated strain grouping differently belonging to South Asian lineage C. auris Clade I. Low numbers of genomic variation point to local and ongoing transmission within the Los Angeles area not specifically within the hospital setting. Collectively, clinical laboratories having the ability to rapidly screen high-risk patients for C. auris and to participate in outbreak investigations by offering strain typing will greatly assist in the control of C. auris transmission within the hospital setting.

Impact of COVID-19 pandemic on antifungal consumption: a multicenter retrospective analysis.

BACKGROUND: In the context of COVID-19 pandemic, antifungal overuse may have occurred in our hospitals as it has been previously reported for antibacterials. METHODS: To investigate the impact of COVID-19 on antifungal consumption, a multicenter retrospective study including four medical sites and 14 intensive care units (ICU) was performed. Antifungal consumption and incidences of invasive fungal diseases before and during COVID-19 pandemic, for non-COVID-19 patients and COVID-19 patients, were described. RESULTS: An increase in voriconazole consumption was observed in 2020 compared with 2019 for both the whole hospital and the ICU (+ 40.3% and + 63.7%, respectively), whereas the incidence of invasive aspergillosis significantly increased in slightly lower proportions in the ICU (+ 46%). Caspofungin consumption also increased in 2020 compared to 2019 for both the whole hospital and the ICU (+ 34.9% and + 17.0%, respectively) with an increased incidence of invasive candidiasis in the whole hospital and the ICU but in lower proportions (+ 20.0% and + 10.9%, respectively). CONCLUSIONS: We observed an increased consumption of antifungals including voriconazole and caspofungin in our hospital during the COVID-19 pandemic and explained in part by an increased incidence of invasive fungal diseases in COVID-19 patients. These results are of utmost importance as it raises concern about the urgent need for appropriate antifungal stewardship activities to control antifungal consumption.

Coumarin-based combined computational study to design novel drugs against Candida albicans.

Candida species cause the most prevalent fungal illness, candidiasis. Candida albicans is known to cause bloodstream infections. This species is a commensal bacterium, but it can cause hospital-acquired diseases, particularly in COVID-19 patients with impaired immune systems. Candida infections have increased in patients with acute respiratory distress syndrome. Coumarins are both naturally occurring and synthetically produced. In this study, the biological activity of 40 coumarin derivatives was used to create a three-dimensional quantitative structure activity relationship (3D-QSAR) model. The training and test minimum inhibitory concentration values of C. albicans active compounds were split, and a regression model based on statistical data was established. This model served as a foundation for the creation of coumarin derivative QSARs. This is a unique way to create new therapeutic compounds for various ailments. We constructed novel structural coumarin derivatives using the derived QSAR model, and the models were confirmed using molecular docking and molecular dynamics simulation.

Candidiasis and Other Bacterial Infections among Patients Diagnosed with Burning Mouth Syndrome.

Background and Objectives: Burning mouth syndrome (BMS) is a state in which a patient experiences intraoral burning or a dysesthetic sensation without clinically evident causative lesions in the oropharyngeal area. The disorder is linked to a variety of conditions, including dry mouth, Candida, and bacterial infections. The aim of this study was to determine the incidence of oral Candida and/or bacterial infections among patients with BMS and whether they have an effect on pain/burning and salivary flow levels. Objectives: (1) Gather patient data regarding the presence of oral infections, dry mouth, and pain levels in the morning, afternoon, and evening periods; (2) data analysis and assessment to determine medians, means, frequencies, correlations, and statistically significant differences between patient groups. Materials and Methods: Overall, 173 patients (23 males and 150 females) with BMS and 13 controls (five males and eight females) took part in the study. We measured pain/burning levels, unstimulated and stimulated salivary flow, the percentage of patients infected with Candida species and/or bacterial species, and the said species growth in Petri dishes. Results: Candida albicans was the most commonly found infection among patients with BMS (n = 28, 16.2%). Overall, 21.4% patients with BMS were diagnosed with either C. albicans or another Candida species. Enterobacter had the richest growth among patients with BMS (7.5% out of the infected 10.4% BMS patients). No statistical significance could be noted between the existence of either Candida species or bacterial species infections and changes in pain/burning and salivary flow levels. Negative correlations were noted between age and unstimulated and stimulated salivary flow, and positive correlations were noted between age and Candida andspecific bacteria species' growth levels. Conclusions: Although patients with present bacterial or Candida infections showed a marginal increase in pain/burning levels, no direct statistically significant associations could be made between the presence of Candida species or other bacteria and the symptoms among patients with BMS.

Sars-Cov-2 infection as a possible risk factor for prosthesis endocarditis: A challenging redo-Bentall for subvalvular abscess.

BACKGROUND: Candida Parapsilosis is an unusual agent of prosthetic endocarditis in immunocompetent individuals but Coronavirus disease 2019 is reported to be associated with a transient immunodeficency that exposes patientes to opportunistic infections. CASE REPORT: We describe a dreadful case of Candida Parapsilosis endocarditis in a transient immunosuppressed patient recently infected with severe acute respiratory syndrome-Coronavirus 2019. CONCLUSION: Considering that the symptoms of Candida Parapsilosis infection and the symptoms of Coronavirus disease-2019 may overlap, it is important never to understimate the non-specific symptoms to improve patient outcome, especially in patient with previous Coronavirurs disease-2019 infection and with prosthetic material grafting.

Molecular Mapping of Antifungal Mechanisms Accessing Biomaterials and New Agents to Target Oral Candidiasis.

Oral candidiasis has a high rate of development, especially in immunocompromised patients. Immunosuppressive and cytotoxic therapies in hospitalized HIV and cancer patients are known to induce the poor management of adverse reactions, where local and systemic candidiasis become highly resistant to conventional antifungal therapy. The development of oral candidiasis is triggered by several mechanisms that determine oral epithelium imbalances, resulting in poor local defense and a delayed immune system response. As a result, pathogenic fungi colonies disseminate and form resistant biofilms, promoting serious challenges in initiating a proper therapeutic protocol. Hence, this study of the literature aimed to discuss possibilities and new trends through antifungal therapy for buccal drug administration. A large number of studies explored the antifungal activity of new agents or synergic components that may enhance the effect of classic drugs. It was of significant interest to find connections between smart biomaterials and their activity, to find molecular responses and mechanisms that can conquer the multidrug resistance of fungi strains, and to transpose them into a molecular map. Overall, attention is focused on the nanocolloids domain, nanoparticles, nanocomposite synthesis, and the design of polymeric platforms to satisfy sustained antifungal activity and high biocompatibility with the oral mucosa.

Organ-specific host differential gene expression analysis in systemic candidiasis: A systems biology approach.

Patients admitted to the hospital with coronavirus disease (COVID-19) are at risk for acquiring mycotic infections in particular Candidemia. Candida albicans (C. albicans) constitutes an important component of the human mycobiome and the most common cause of invasive fungal infections. Invasive yeast infections are gaining interest among the scientific community as a consequence of complications associated with severe COVID-19 infections. Early identification and surveillance for Candida infections is critical for decreasing the COVID-19 mortality. Our current study attempted to understand the molecular-level interactions between the human genes in different organs during systematic candidiasis. Our research findings have shed light on the molecular events that occur during Candidiasis in organs such as the kidney, liver, and spleen. The differentially expressed genes (up and down-regulated) in each organ will aid in designing organ-specific therapeutic protocols for systemic candidiasis. We observed organ-specific immune responses such as the development of the acute phase response in the liver; TGF-pathway and genes involved in lymphocyte activation, and leukocyte proliferation in the kidney. We have also observed that in the kidney, filament production, up-regulation of iron acquisition mechanisms, and metabolic adaptability are aided by the late initiation of innate defense mechanisms, which is likely related to the low number of resident immune cells and the sluggish recruitment of new effector cells. Our findings point to major pathways that play essential roles in specific organs during systemic candidiasis. The hub genes discovered in the study can be used to develop novel drugs for clinical management of Candidiasis.

Fatal invasive candidiasis in COVID-19 patient with severe bleeding and extensively drug-resistant Klebsiella enterobacter.

INTRODUCTION: Multi-organ dysfunction caused by thromboembolic complications may complicate the course of SARS-CoV-2 infection. Most patients require anticoagulant therapy which predisposes them to the development of hemorrhagic syndrome. In critically ill COVID-19 patients secondary infections due to opportunistic pathogens are associated with a high mortality rate. CASE REPORT: Herein, we present a COVID-19 patient with severe hemorrhage at unusual sites complicated with invasive candidiasis and an extensively drug-resistant (XDR) strain of Klebsiella enterobacter. CONCLUSIONS: Clinicians should be aware of the possibility for invasive fungal infections in severely ill patients with SARS-CoV-2 infection due to pre-existing conditions, risk factors, and COVID-19 associated pathological mechanisms. Management of invasive candidiasis is challenging because of the high prevalence of comorbidities, risk of toxicities, and drug interactions.