Environmental reservoirs of the drug-resistant pathogenic yeast Candida auris.

Candia auris is an emerging human pathogenic yeast; yet, despite phenotypic attributes and genomic evidence suggesting that it probably emerged from a natural reservoir, we know nothing about the environmental phase of its life cycle and the transmission pathways associated with it. The thermotolerant characteristics of C. auris have been hypothesised to be an environmental adaptation to increasing temperatures due to global warming (which may have facilitated its ability to tolerate the mammalian thermal barrier that is considered a protective strategy for humans against colonisation by environmental fungi with pathogenic potential). Thus, C. auris may be the first human pathogenic fungus to have emerged as a result of climate change. In addition, the release of antifungal chemicals, such as azoles, into the environment (from both pharmaceutical and agricultural sources) is likely to be responsible for the environmental enrichment of resistant strains of C. auris; however, the survival and dissemination of C. auris in the natural environment is poorly understood. In this paper, we critically review the possible pathways through which C. auris can be introduced into the environment and evaluate the environmental characteristics that can influence its persistence and transmission in natural environments. Identifying potential environmental niches and reservoirs of C. auris and understanding its emergence against a backdrop of climate change and environmental pollution will be crucial for the development of effective epidemiological and environmental management responses.

Critically ill patients with COVID-19 show lung fungal dysbiosis with reduced microbial diversity in patients colonized with Candida spp.

BACKGROUND: The COVID-19 pandemic has intensified interest in how the infection affects the lung microbiome of critically ill patients and how it contributes to acute respiratory distress syndrome (ARDS). We aimed to characterize the lower respiratory tract mycobiome of critically ill patients with COVID-19 in comparison to patients without COVID-19. METHODS: We performed an internal transcribed spacer 2 (ITS2) profiling with the Illumina MiSeq platform on 26 respiratory specimens from patients with COVID-19 as well as from 26 patients with non-COVID-19 pneumonia. RESULTS: Patients with COVID-19 were more likely to be colonized with Candida spp. ARDS was associated with lung dysbiosis characterized by a shift to Candida species colonization and a decrease of fungal diversity. We also observed higher bacterial phylogenetic distance among taxa in colonized patients with COVID-19. In patients with COVID-19 not colonized with Candida spp., ITS2 amplicon sequencing revealed an increase of Ascomycota unassigned spp. and 1 Aspergillus spp.-positive specimen. In addition, we found that corticosteroid therapy was frequently associated with positive Galactomannan cell wall component of Aspergillus spp. among patients with COVID-19. CONCLUSION: Our study underpins that ARDS in patients with COVID-19 is associated with lung dysbiosis and that an increased density of Ascomycota unassigned spp. is present in patients not colonized with Candida spp.

Clinical impact of Candida respiratory tract colonization and acute lung infections in critically ill patients with COVID-19 pneumonia.

Coronavirus disease 2019 (COVID-19), which is attributable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been causing a worldwide health issue. Airways colonization by Candida spp. is prevalent among patients on automatic ventilation in intensive care units (ICUs). This research aimed to ascertain the risk factors and roles of Candida spp. respiratory tract colonization, and Candida lung infection during the progression of COVID-19 pneumonia in critically ill patients. In total, Candida spp. were recovered in 69 from 100 immunosuppressed patients with COVID-19. Bronchoscopy was used to collect the Bronchoalveolar lavage (BAL) specimens. For the identification of Candida spp. PCR sequencing was done using the ITS1 and ITS4 primers. The amplification of the HWP1 gene was conducted to identify the Candida albicans complex. The antifungal activities of fluconazole, itraconazole, voriconazole, amphotericin B and caspofungin against Candida spp. were evaluated using the Clinical and Laboratory Standards Institute M60. In 63.77% of the patients, Candida respiratory colonization at D0 and D14 had no impact on the severity of COVID-19. In comparison to C. albicans strains, Candida respiratory disorder with C. glabrata had influenced the severity of COVID-19 for critically ill patients following adjustment for the risk factors of COVID-19 (P < 0.05). Amphotericin B and caspofungin showed superior activity against all Candida spp. All antifungal agents showed 100% sensitivity against the two C. africana strains. Our observation on patients who used automatic ventilation, respiratory colonization by Candida spp. was not seen to influence the infection or death caused by COVID-19. Amphotericin B and caspofungin showed superior activity against all Candida spp. and were recommended for the treatment regime of pulmonary candidiasis associated with COVID-19 infection. Although "Candida pneumonia" is rarely being reported in critically ill patients, Candida airway colonization mainly by Candida albicans is common especially among patients with diabetes, malignancies, and kidney disorders.

COVID-19-Associated Candidiasis: Possible Patho-Mechanism, Predisposing Factors, and Prevention Strategies.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is threatening public health. A large number of affected people need to be hospitalized. Immunocompromised patients and ICU-admitted patients are predisposed to further bacterial and fungal infections, making patient outcomes more critical. Among them, COVID-19-associated candidiasis is becoming more widely recognized as a part of severe COVID-19 sequelae. While the molecular pathophysiology is not fully understood, some factors, including a compromised immune system, iron and zinc deficiencies, and nosocomial and iatrogenic transmissions, predispose COVID-19 patients to candidiasis. In this review, we discuss the existing knowledge of the virulence characteristics of Candida spp. and summarize the key concepts in the possible molecular pathogenesis. We analyze the predisposing factors that make COVID-19 patients more susceptible to candidiasis and the preventive measures which will provide valuable insights to guide the effective prevention of candidiasis in COVID-19 patients.

A Chronic Autochthonous Fifth Clade Case of Candida auris Otomycosis in Iran.

Candida auris, a multidrug-resistant nosocomial pathogen, has emerged globally with high morbidity and mortality among immunocompromised individuals and COVID19 hospitalized patients. Five major clades of C. auris have been previously described. The fifth clade is exclusively found in Iran where C. auris isolates are genetically distinct from other clades by > 200,000 single-nucleotide polymorphisms. The origin of C. auris remains unclear, and limited clinical data are available at present regarding clade V infection or colonization. Herein, another case of otomycosis in Iran caused by an isolate of C. auris belonging to the fifth clade is reported. Genotyping revealed that the obtained C. auris isolate from Isfahan clustered with earlier clade V isolates from Babol, cities around 600 km separated, which indicates that C. auris clade V is established in Iran. C. auris is thought to exist more commonly in Iran, given that limited diagnostic capacity in the country has probably curbed the identification of more C. auris cases. Therefore, surveillance of the environment, patients and healthcare facilities in different geographical regions in Iran is urgently required.

Nanopore Genome Sequencing and Variant Analysis of the Susceptible Candida auris Strain L1537/2020, Salvador, Brazil.

Candida auris has been reported worldwide, but only in December 2020, the first strain from a COVID-19 patient in Brazil was isolated. Here, we describe the genome sequence of this susceptible C. auris strain and performed variant analysis of the genetic relatedness with strains from other geographic localities.

Candida auris Invasive Infections during a COVID-19 Case Surge.

Clinical cases of C. auris noted during a COVID-19 surge led to an epidemiological, clinical, and genomic investigation. Evaluation identified a close genetic relationship but inconclusive epidemiologic link between all cases. Prolonged hospitalization due to critical illness from COVID-19 and use of antimicrobials may have contributed to clinical infections.

First reported outbreak of the emerging pathogen Candida auris in Canada.

BACKGROUND: Candida auris was first described in Japan in 2009 and has since been detected in over 40 countries. The yeast is concerning for multiple reasons, primarily: (1) challenges with accurate identification; (2) reported multidrug resistance; (3) published mortality rates of 30%-60%; and (4) persistence in the environment associated with human transmission. We report the emergence of a healthcare-associated cluster in the Greater Vancouver area in 2018 and describe the measures implemented to contain its transmission. METHODS: Cases were identified through passive and ring surveillance of affected wards. Positive isolates were sent to provincial and national reference laboratories for confirmation and genomic characterization. Extensive infection control measures were implemented immediately after the initial case was identified. RESULTS: Four cases were identified during the outbreak. In a 4-month period, over 700 swabs were collected in order to screen 180 contacts. Whole genome sequencing concluded that all isolates clustered together and belonged to the South Asian clade. No isolates harbored FKS gene mutations associated with resistance to echinocandins. Infection control measures, including surveillance, education, cleaning and/or disinfection, patient cohorting, isolation, and hand hygiene, effectively contained the outbreak; it was declared over within 2 months. CONCLUSIONS: The spread of C auris in healthcare facilities has not spared Canadian institutions. Our experience demonstrates that strict infection control measures combined with microbiological screening can effectively halt transmission in healthcare centers. The necessity of active prospective screening remains unclear.

Increased incidence of candidemia in a tertiary care hospital with the COVID-19 pandemic.

BACKGROUND: The incidence of candidemia in our hospital has been stable over an 18-year period (1.3 episodes per 1000 admissions). Since March 2020, we have observed an increase in cases of candidemia. METHODS: In March 2020, the hospital was prepared to receive patients with COVID-19, with cancellation of elective procedures, discharge of less sick patients and the activation of beds for COVID-19. We compared the incidence of candidemia in 2 periods: from January 2019 to February 2020 (period 1) and from March to September 2020 (period 2). RESULTS: We diagnosed 41 episodes of candidemia, 16 in period 1 and 25 in period 2 (9 COVID-19 patients). Compared with non-COVID-19 patients, COVID-19 patients with candidemia were more likely to be under mechanical ventilation (100% vs. 34.4%, P < .001). The median number of monthly admissions in period 1 and 2 was 723 (interquartile range 655-836) and 523 (interquartile range 389-574), respectively. The incidence of candidemia (per 1000 admissions) was 1.54 in period 1 and 7.44 in period 2 (P < .001). In period 2, the incidence of candidemia (per 1000 admissions) was 4.76 if we consider only cases of candidemia in non-COVID-19 patients, 2.68 if we consider only cases of candidemia in COVID-19 patients and 14.80 considering only admissions of patients with COVID-19. CONCLUSIONS: The increase in the incidence of candidemia in our hospital may be attributed to 2 factors: a reduction in the number of admissions (denominator) and the occurrence of candidemia in COVID-19 patients.

Oropharyngeal candidiasis in hospitalised COVID-19 patients from Iran: Species identification and antifungal susceptibility pattern.

BACKGROUND: Emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. Apparently, the novel coronavirus (SARS-CoV-2) is armed by special abilities to spread and dysregulate the immune mechanisms. The likelihood of oropharyngeal candidiasis (OPC) development in COVID-19 patients with a list of attributable risk factors for oral infections has not yet been investigated. OBJECTIVES: We here aim to investigate the prevalence, causative agents and antifungal susceptibility pattern of OPC in Iranian COVID-19 patients. PATIENTS AND METHODS: A total of 53 hospitalised COVID-19 patients with OPC were studied. Relevant clinical data were mined. Strain identification was performed by 21-plex PCR and sequencing of the internal transcribed spacer region (ITS1-5.8S-ITS2). Antifungal susceptibility testing to fluconazole, itraconazole, voriconazole, amphotericin B, caspofungin, micafungin and anidulafungin was performed according to the CLSI broth dilution method. RESULTS: In 53 COVID-19 patients with OPC, cardiovascular diseases (52.83%) and diabetes (37.7%) were the principal underlying conditions. The most common risk factor was lymphopaenia (71%). In total, 65 Candida isolates causing OPC were recovered. C albicans (70.7%) was the most common, followed by C glabrata (10.7%), C dubliniensis (9.2%), C parapsilosis sensu stricto (4.6%), C tropicalis (3%) and Pichia kudriavzevii (=C krusei, 1.5%). Majority of the Candida isolates were susceptible to all three classes of antifungal drugs. CONCLUSION: Our data clarified some concerns regarding the occurrence of OPC in Iranian COVID-19 patients. Further studies should be conducted to design an appropriate prophylaxis programme and improve management of OPC in critically ill COVID-19 patients.

Alterations in Fecal Fungal Microbiome of Patients With COVID-19 During Time of Hospitalization until Discharge.

BACKGROUND & AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects intestinal cells, and might affect the intestinal microbiota. We investigated changes in the fecal fungal microbiomes (mycobiome) of patients with SARS-CoV-2 infection during hospitalization and on recovery. METHODS: We performed deep shotgun metagenomic sequencing analysis of fecal samples from 30 patients with coronavirus disease 2019 (COVID-19) in Hong Kong, from February 5 through May 12, 2020. Fecal samples were collected 2 to 3 times per week from time of hospitalization until discharge. We compared fecal mycobiome compositions of patients with COVID-19 with those from 9 subjects with community-acquired pneumonia and 30 healthy individuals (controls). We assessed fecal mycobiome profiles throughout time of hospitalization until clearance of SARS-CoV-2 from nasopharyngeal samples. RESULTS: Patients with COVID-19 had significant alterations in their fecal mycobiomes compared with controls, characterized by enrichment of Candia albicans and a highly heterogeneous mycobiome configuration, at time of hospitalization. Although fecal mycobiomes of 22 patients with COVID-19 did not differ significantly from those of controls during times of hospitalization, 8 of 30 patients with COVID-19 had continued significant differences in fecal mycobiome composition, through the last sample collected. The diversity of the fecal mycobiome of the last sample collected from patients with COVID-19 was 2.5-fold higher than that of controls (P < .05). Samples collected at all timepoints from patients with COVID-19 had increased proportions of opportunistic fungal pathogens, Candida albicans, Candida auris, and Aspergillus flavus compared with controls. Two respiratory-associated fungal pathogens, A. flavus and Aspergillus niger, were detected in fecal samples from a subset of patients with COVID-19, even after clearance of SARS-CoV-2 from nasopharyngeal samples and resolution of respiratory symptoms. CONCLUSIONS: In a pilot study, we found heterogeneous configurations of the fecal mycobiome, with enrichment of fungal pathogens from the genera Candida and Aspergillus, during hospitalization of 30 patients with COVID-19 compared with controls. Unstable gut mycobiomes and prolonged dysbiosis persisted in a subset of patients with COVID-19 up to 12 days after nasopharyngeal clearance of SARS-CoV-2. Studies are needed to determine whether alterations in intestinal fungi contribute to or result from SARS-CoV-2 infection, and the effects of these changes in disease progression.